WO2001055131A2

WO2001055131A2 - Prodigiosin-derivatives as neoplastic and anti-viral agents

Info

Publication number: WO2001055131A2
Application number: PCT/CA2001/000085
Authority: WO
Inventors: Madiraju S. R. Murthy; Nancy A. E. Steenaart; Roy A. Johnson; Gordon C. Shore
Original assignee: Gemin X Biotechnologies Inc
Current assignee: Gemin X Pharmaceuticals Canada Inc
Priority date: 2000-01-26
Filing date: 2001-01-24
Publication date: 2001-08-02
Anticipated expiration: 2002-07-26
Also published as: AU2991201A; US6407244B1; NZ520361A; KR20020072295A; CA2398173A1; IL150817A0; EP1255753B1; AU780647B2; NO20023486D0; US20030009032A1; PL356932A1; US6602879B2; WO2001055131A3; CN1419553A; EP1431286A3; DE60103978D1; JP2003523352A; CZ20022604A3; MXPA02007271A; SK10952002A3

Abstract

The present invention relates to novel Pyrrole-Type compounds, compositions comprising Pyrrole-Type compounds, and methods useful for treating or preventing cancer or a neoplastic disorder comprising administering a composition comprising a Pyrrole-Type compound. The compounds, compositions, and methods of the invention are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The present invention also relates to novel Pyrrole-Type compounds, compositions, and methods useful for treating or preventing a viral infection. The compounds, compositions, and methods of the invention are also useful for inhibiting the replication and/or infectivity of a virus.

Description

PYRROLE-TYPE COMPOUNDS, COMPOSITIONS, AND METHODS FOR TREATING CANCER OR VIRAL DISEASES

1. FIELD OF THE INVENTION

The present invention relates to Pyrrole-Type compounds, compositions comprising Pyrrole-Type compounds, and methods useful for treating or preventing cancer or a neoplastic disorder comprising administering a composition comprising a Pyrrole-Type compound. The compounds, compositions, and methods of the invention are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The present invention also relates to Pyrrole-Type compounds, compositions, and methods useful for treating or preventing a viral infection. The compounds, compositions, and methods of the invention are also useful for inhibiting the replication or infectivity of a virus.

2. BACKGROUND OF THE INVENTION

2.1. CANCER AND NEOPLASTIC DISEASE

Cancer affects approximately 20 million adults and children worldwide, and this year, more than 9 million new cases will be diagnosed (International Agency for Research on Cancer; www.irac.fr). According to the American Cancer Society, about 563,100

Americans are expected to die of cancer this year, more thanl500 people a day. Since 1990, in the United States alone, nearly five million lives have been lost to cancer, and approximately 12 million new cases have been diagnosed.

Currently, cancer therapy involves surgery, chemotherapy and/or radiation treatment to eradicate neoplastic cells in a patient (see, for example, Stockdale, 1998, "Principles of Cancer Patient Management", in Scientific American: Medicine, vol. 3, Rubenstein and Federman, eds., Chapter 12, Section IV). All of these approaches pose significant drawbacks for the patient. Surgery, for example, may be contraindicated due to the health of the patient or may be unacceptable to the patient. Additionally, surgery may not completely remove the neoplastic tissue. Radiation therapy is effective only when the irradiated neoplastic tissue exhibits a higher sensitivity to radiation than normal tissue, and radiation therapy can also often elicit serious side effects. (Id.) With respect to chemotherapy, there are a variety of chemotherapeutic agents available for treatment of neoplastic disease. However, despite the availability of a variety of chemotherapeutic agents, chemotherapy has many drawbacks (see, for example, Stockdale, 1998, "Principles Of Cancer Patient Management" in Scientific American Medicine, vol. 3, Rubenstein and Federman, eds., ch. 12, sect. 10). Almost all chemotherapeutic agents are toxic, and chemotherapy causes significant, and often dangerous, side effects, including severe nausea, bone marrow depression, immunosuppression, etc. Additionally, many tumor cells are resistant or develop resistance to chemotherapeutic agents through multi-drug resistance. Tamura et al, JP93086374, discloses metacycloprodigiosin and/or prodigiosin-25C as being useful for treating leukemia, but provides data for only prodigiosin-25C activity against L-5178Y cells in vitro. Hirata et al., JP-10120562, discloses the use of cycloprodigiosin as an inhibitor of the vacuolar ATPase proton pump and states that cycloprodigiosin may have anti-tumor enhancing activity. Hirata et al, JP-10120563 discloses the use of cycloprodigiosin as a therapeutic drug for leukemia, as an immunosuppressant, and as an apoptosis inducer. JP61034403, to Kirin Brewery Co. Ltd, describes prodigiosin for increasing the survival time of mice with leukemia. Boger, 1988, J. Org. Chem. 53:1405-1415 discloses in vitro cytotoxic activity of prodigiosin, prodigiosene, and 2-methyl-3-pentylprodigiosene against mouse P388 leukemia cells. The National Cancer Institute, http://dtp.nci.nih.gov, discloses data obtained from the results of a human-tumor-cell-line screen, including screening of butylcycloheptyl-prodiginine HCI; however, the screen provides no indication that the compounds of the screen are selective for cancer cells (e.g., as compared to normal cells). Therefore, there is a significant need in the art for novel compounds and compositions, and methods that are useful for treating cancer or neoplastic disease with reduced or without the aforementioned side effects. Further, there is a need for cancer treatments that provide cancer-cell-specific therapies with increased specificity and decreased toxicity.

2.2. VIRUSES AND DISEASE

In addition to cancer, an enormous number of human and animal diseases result from virulent and opportunistic viral infections (see Belshe (Ed.) 1984 Textbook of Human Virology, PSG Publishing, Littleton, MA). Viral diseases of a wide array of tissues, including the respiratory tract, CNS, skin, genitourinary tract, eyes, ears, immune system, gastrointestinal tract, and musculoskeletal system, affect a vast number of humans of all ages (see Table 328-2 In: Wyngaarden and Smith, 1988, Cecil Textbook of Medicine, 18^lh Ed., W.B. Saunders Co., Philadelphia, pp.1750- 1753).

Although considerable effort has been invested in the design of effective anti- viral therapies, viral infections continue to threaten the lives of millions of people worldwide. In general, attempts to develop anti- viral drugs have focused on several stages of viral life cycle (See e.g., Mitsuya, H., et al, 1991, FASEB J. 5:2369-2381, discussing HIV). However, a common drawback associated with using of many current anti- viral drugs is their deleterious side effects, such as toxicity to the host or resistance by certain viral strains.

Accordingly, there is a need in the art for anti- viral compounds, compositions, and methods that allow for safe and effective treatment of viral disease without the above-mentioned disadvantages.

Citation or identification of any reference in Section 2 of this application is not an admission that such reference is available as prior art to the present invention.

3. SUMMARY OF THE INVENTION FORMULA I The present invention encompasses novel compounds having the general

Formula (I):

and pharmaceutically acceptable salts thereof, wherein: each Ri is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C_rC₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_nR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCI₃;

R₃ is selected from the group consisting of -H, -C^ straight chain alkyl, -CH(R₁₄)(R,₅) wherein R₁₄ and R_I5 are independently C C₁₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups;

R₁₀ is selected from the group consisting of C_rC₄ straight or branched chain alkyl and -C₆H₅; R. , and R₁₂ are independently C_rC₃ straight or branched chain alkyl;

R₁₆ and R₁₇ is -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: butyl-meta-cycloheptylprodiginine, metacycloprodigiosin,

4-ethoxy-5-((3,5-nonamethylene-2H-pyrrol-2-ylidene)methyl)-2,2^,-bi-lH-pyrrole, or 4-propoxy-5-((3,5-nonamethylene-2H-pyrrol-2-ylidene)methyl)-2,2'-bi-lH-pyrrole.

The compounds of Formula (I) and pharmaceutically acceptable salts thereof are useful for treating or preventing cancer or neoplastic disease in a patient in need of such treatment or prevention. The compounds of Formula (I) and pharmaceutically acceptable salts thereof are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The compounds of Formula (I) and pharmaceutically acceptable salts thereof are useful for treating or preventing a viral infection in a patient in need of such treatment or prevention. The compounds of Formula (I) and pharmaceutically acceptable salts thereof are also useful for inhibiting the replication or infectivity of a virus.

The present invention provides compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C_rC₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_nR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₃ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH(R₁₄)(R₁₅) wherein R₁₄ and R₁₅ are independently C,-C₁₂ straight chain alkyl, -C(O)C_r C₉ straight chain alkyl, -CH(OH)C_rC₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the - CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups; R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R_π and R₁₂ are independently C,-C₃ straight or branched chain alkyl;

R,₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: butyl-meta-cycloheptylprodiginine, metacycloprodigiosin,

4-ethoxy-5-((3,5-nonamethylene-2H-pyrrol-2-ylidene)methyl)-2, 2'-bi-lH-pyrrole, or 4-propoxy-5-((3,5-nonamethylene-2H-pyrrol-2-ylidene)methyl)-2, 2'-bi-lH-pyrrole.

The compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (I) or a pharmaceutically acceptable salt thereof are useful for treating or preventing cancer or neoplastic disease in a patient in need of such treatment or prevention. These compositions are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (I) or a pharmaceutically acceptable salt thereof are also useful for treating or preventing a viral infection in a patient in need of such treatment or prevention. These compositions are also useful for inhibiting the replication or infectivity of a virus.

The invention further provides methods for treating or preventing cancer or neoplastic disease in a patient comprising administering to a patient in need of such treatment or prevention a composition comprising a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_πR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₃ is selected from the group consisting of -H, 0,-0,₂ straight chain alkyl, -CH(R*₄)(R₁₅) wherein R₁₄ and R,₅ are independently C_rC_I2 straight chain alkyl, -C(O)C_r C₉ straight chain alkyl, -CH(OH)C_rC₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H_S, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups; R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R_n and R₁₂ are independently C_rC₃ straight or branched chain alkyl; m is an integer ranging from 1 to 5; and when m is 3 and R₂ is -CH₂CH₃, then R₁₆ is -H or -CH₃ and R₁₇ is -H; when m is 3 and R₂ is -CH₃, then R₁₆ is -H or -CH₃ and R₁₇ is -H or -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R₁₆ and R₁₇ are -H only; with the proviso that the compound of Formula (I) is not: metacycloprodigiosin.

The invention further provides methods for inhibiting the growth of a cancer cell or neoplastic cell comprising a contacting a cancer cell or neoplastic cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (I) or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (I) : each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H_s, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, -C^ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_uR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₃ is. selected from the group consisting of -H, C_]-C₁₂ straight chain alkyl, -CH(R₁₄)(R₁₅) wherein R₁₄ and R_I5 are independently C,-C₁₂ straight chain alkyl, -C(O)C_r C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(Cl)C_rC₉ straight 'chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups;

R₁₀ is selected from the group consisting of -C₄ straight or branched chain alkyl and -C₆H₅;

R_u and R₁₂ are independently C,-C₃ straight or branched chain alkyl; m is an integer ranging from 1 to 5; when m is 3 and R₂ is -CH₂CH₃, then R₁₆is -H or -CH₃ and R₁₇ is -H; when m is 3 and R₂ is -CH₃, then R₁₆ is -H or -CH₃ and R₁₇ is -H or -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R₁₆ and R_I7 are -H only; with the proviso that the compound of Formula (I) is not: metacycloprodigiosin.

The invention further provides methods for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C_rC_I2 straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_uR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₃ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH(R₁₄)(R₁₅) wherein R₁₄ and R₁₅ are independently C,-C₁₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(Cl)C_rC₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the

-CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups;

R,₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅; R_{ , and R₁₂ are independently C,-C₃ straight or branched chain alkyl; m is an integer ranging from 1 to 5; and when m is 3 and R₂ is -CH₂CH₃, then R₁₆ is -H or -CH₃ and R₁₇ is -H; when m is 3 and R₂ is -CH₃, then R₁₆ is -H or -CH₃ and R₁₇ is -H or -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R₁₆ and R₁₇ are -H only.

The invention further provides methods for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (I) or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C_I2 straight chain alkyl, -CH₂C₆H₅, -SiR.₀R.*R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; R₃ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, - CH(R₁₄)(R₁₅) wherein R₁₄ and R₁₅ are independently C,-C₁₂ straight chain alkyl, -C(O)C_rC₉ straight chain alkyl, -CH(OH)C_rC₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-ρyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups;

R₁₀ is selected from the group consisting of -C₄ straight or branched chain alkyl and - H₅;

R,, and R₁₂ are independently C_rC₃ straight or branched chain alkyl; m is an integer ranging from 1 to 5; and when m is 3 and R₂ is -CH₂CH₃, then R₁₆ is -H or -CH₃ and R₁₇ is -H; when m is 3 and R₂ is -CH₃, then R₁₆ is -H or -CH₃ and R₁₇ is -H or -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R₁₆ and R₁₇ are -H only.

FORMULA II

The present invention still further provides novel compounds having the general Formula (II):

II and pharmaceutically acceptable salts thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl,

-CH₂C₆H₅, -SiR₁₀R„R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₄ is selected from the group consisting of -H and C,-C₁₂ straight chain alkyl; R₅ is selected from the group consisting of -H, C C₄ straight chain alkyl and -C₆H₅; R₁₀ is selected from the group consisting of -C_rC₄, straight or branched chain alkyl and -C₆H₅;

R_n and R₁₂ are independently C,-C₃ straight or branched chained alkyl; and n is an integer ranging from 1 to 6; with the proviso that the compound of Formula (II) is not: cycloprodigiosin, or

4-ethyl-2,4,5,6-tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl-)-2H-pyrrol-2- ylidene)m ethyl)- 1 -methyl-cyclopenta(c)pyrrole.

The compounds of Formula (II) and pharmaceutically acceptable salts thereof are useful for treating or preventing cancer or neoplastic disease in a patient in need of such treatment or prevention. The compounds of Formula (II) and pharmaceutically acceptable salts thereof are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The compounds of Formula (II) and pharmaceutically acceptable salts thereof are useful for treating or preventing a viral infection in a patient in need of such treatment or prevention. The compounds of Formula (II) and pharmaceutically acceptable salts thereof are also useful for inhibiting the replication or infectivity of a virus.

The present invention further provides compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula (II) or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (II): each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃,

-CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C_rC₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR.₀R_πR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; R₄ is selected from the group consisting of -H and C,-C₁₂ straight chain alkyl;

R₅ is selected from the group consisting of -H, C_rC₄ straight chain alkyl and -C₆H₅;

R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl, and -C₆H₅;

R_n and R₁₂ are independently selected from the group consisting of -CH₃, -CH₂CH₃, and -C₃H₇; and n is an integer ranging from 1 to 6; with the proviso that the compound of Formula (II) is not: cycloprodigiosin, or

4-ethyl-2,4,5,6-tetrahydro-3-((3-methoxy-5-(lH-pyrrol-2-yl-)-2H-pyrrol-2- ylidene)methyl)- 1 -methyl-cyclopenta(c)pyrrole. The compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (IT) or a pharmaceutically acceptable salt thereof are useful for treating or preventing cancer or neoplastic disease in a patient in need of such treatment or prevention. These compositions are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (II) or a pharmaceutically acceptable salt thereof are useful for treating or preventing a viral infection in a patient in need of such treatment or prevention. These compositions are also useful for inhibiting the replication and/or infectivity of a virus.

The invention provides methods for treating or preventing cancer or a neoplastic disease comprising administering to a patient in need of such treatment or prevention a composition comprising a therapeutically effective amount of a compound of Formula (II) or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H_s, and -C(O)CH₃; R₂ is selected from the group consisting of -H, C,-C_I2 straight chain alkyl,

-CH₂C₆H₅, -SiR₁₀R_nR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₄ is selected from the group consisting of -H and C,-C_I2 straight chain alkyl;

R₅ is selected from the group consisting of -H, C,-C₄ straight chain alkyl and -C₆H₅; R₁₀ is selected from the group consisting of C_rC₄ straight or branched chain alkyl and -C₆H₅;

R_n and R₁₂ are independently selected from the group consisting of C,-C₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6; with the proviso that the compound of Formula (ET) is not: cycloprodigiosin.

The invention provides methods for inhibiting the growth of a cancer cell or neoplastic cell comprising a contacting a cancer cell or neoplastic cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (II) or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C^C^ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_MR_I2> -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; R₄ is selected from the group consisting of -H and C_rC₁₂ straight chain alkyl;

R₅ is selected from the group consisting of -H, C C₄ straight chain alkyl and -C₆H₅;

R,₀ is selected from the group consisting of C_rC₄ straight or branched chain alkyl and -C₆H₅; R, , and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and n is a integer from 1 to 6; with the proviso that the compound of Formula (II) is not: cycloprodigiosin.

The invention provides methods for treating or preventing a viral infection comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (II) or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂ H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, -C,-, straight chain alkyl, -CH₂C₆H₅, -SiR_I0R..R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₄ is selected from the group consisting of -H and C,-C₁₂ straight chain alkyl; R₅ is selected from the group consisting of -H, C,-C₄ straight chain alkyl and -C₆H₅;

R,₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl, and -C₆H₅;

R,, and R_I2 are independently C,-C₃ straight or branched chain alkyl; and n is a integer from 1 to 6. The invention provides methods for inhibiting the replication or infectivity of a virus comprising contacting a virus or a virus-infected cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (II) or a pharmaceutically acceptable salt thereof, wherein: each R[ is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR_I0R,,R_I2, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₄ is selected from the group consisting of -H and C,-C,₂ straight chain alkyl; R₅ is selected from the group consisting of -H, C,-C₄ straight chain alkyl and -C₆H₅; R₁₀ is selected from the group consisting of C_rC₄ straight or branched chain alkyl and C₆H₅;

R_π and R_I2 are independently C,-C₃ straight or branched chain alkyl; and n is a integer from 1 to 6.

FORMULA III

The present invention still further provides novel compounds having the general Formula (HI):

III

and pharmaceutically acceptable salts thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; R₂ is selected from the group consisting of -H, C_rC*₂ straight chain alkyl,

-CH₂C₆H₅, -SiR.₀R*.R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₅ is selected from the group consisting of -H, C,-C₆ straight chain alkyl and -C₆H₅; R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R_u and R_I2 are independently C,-C₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6; with the proviso that the compound of Formula (III) is not: orthobutylcycloheptylprodiginine, 4-methoxy-5-((4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH-pynole),

4-methoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH- pyrrole),

4-ethoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2^*-bi-lH- pyrcole), or 4-propoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2, 2'-bi-lH- pyrrole).

The compounds of Formula (HI) and pharmaceutically acceptable salts thereof are useful for treating or preventing cancer or neoplastic disease in a patient in need of such treatment or prevention. The compounds of Formula (HI) and pharmaceutically acceptable salts thereof are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The compounds of Formula (EI) and pharmaceutically acceptable salts thereof are useful for treating or preventing a viral infection in a patient in need of such treatment or prevention. The compounds of Formula (HI) and pharmaceutically acceptable salts thereof are also useful for inhibiting the replication or infectivity of a virus.

The present invention further provides compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula (III) or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_nR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₅ is selected from the group consisting of -H, C,-C₆ straight chain alkyl and -C₆H₅; R₁₀ is selected from the group consisting of C,-C₆ straight or branched chain alkyl and -C₆H₅;

R_n and R₁₂ are independently C_rC₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6; with the proviso that the compound of Formula (IH) is not: orthobutylcycloheptylprodiginine;

4-methoxy-5-((4,5,6,7 -tetrahydro-2H -indol-2-ylidene)methyl)-2, 2'-bi lH-pyrrole),

4-methoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2, 2'-bi 1H- pyrrole),

4-ethoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2, 2'-bi )H- pyrrole), or

4-propoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2, 2'-bi 1H- pyrrole).

The compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (IH) or a pharmaceutically acceptable salt thereof are useful for treating or preventing cancer or neoplastic disease in a patient in need of such treatment or prevention. ^' These compositions are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (HI) or a pharmaceutically acceptable salt thereof are useful for treating or preventing a viral infection in a patient in need of such treatment or prevention. These compositions are also useful for inhibiting the replication or infectivity of a virus.

The invention further provides methods for treating or preventing cancer or a neoplastic disease comprising administering to a patient in need of such treatment or prevention a composition comprising a therapeutically effective amount of a compound of Formula (IH) or a pharmaceutically acceptable salt thereof, wherein: each R_j is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃,

-CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_πR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; R_s is selected from the group consisting of -H, C,-C₆ straight chain alkyl and -C₆H₅;

R₁₀ is selected from the group consisting of C_rC₄ straight or branched chain alkyl and -C₆H₅;

R_u and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6. The invention further provides methods for inhibiting the growth of a cancer cell or neoplastic cell comprising a contacting a cancer cell or neoplastic cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (HI) or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H_s, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C_rC₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_uR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₅ is selected from the group consisting of -H, C_rC₆ straight chain alkyl and -C₆H₅; R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R_M and R₁₂ are independently C_rC₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6.

The invention further provides methods for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (HI) and pharmaceutically acceptable salts thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C^C^ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R„R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH,CCl₃;

R₅ is selected from the group consisting of -H, C^ straight chain alkyl and -C₆H₅; R_I0 is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R_n and R₁₂ are independently C_rC₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6.

The invention further provides methods for inhibiting the replication or infectivity of a virus comprising contacting a virus or a virus-infected cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (HI) or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; R₂ is selected from the group consisting of -H, C,-C_I2 straight chain alkyl,

R₅ is selected from the group consisting of -H, C,-C₆ straight chain alkyl and -C₆H₅;

R_u and R₁₂ are independently C_rC₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6.

FORMULA IV

The present invention encompasses novel compounds having the general Formula (TV):

and pharmaceutically acceptable salts thereof, wherein:

R₂ is selected from the group consisting of -H, C,-C_]2 straight chain alkyl, -CH₂C₆H₅, -SiR,oR„R₁₂, -C(O)CH_3> -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; R_I0 is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R_u and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and p is as integer from 6 to 8; with the proviso that the compound of Formula (IV) is not: cyclononylprodiginine, methylcyclooctylprodiginine, methylcyclodecylprodiginine, ethylcyclononylprodiginine,

R39FF, R39MF, R39SF, 61 OFF, or 610MF.

The compounds of Formula (IV) and pharmaceutically acceptable salts thereof are useful for treating or preventing cancer or neoplastic disease in a patient in need of such treatment or prevention. The compounds of Formula (TV) and pharmaceutically acceptable salts thereof are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The compounds of Formula (IV) and pharmaceutically acceptable salts thereof are useful for treating or preventing a viral infection in a patient in need of such treatment or prevention. The compounds of Formula (IV) and pharmaceutically acceptable salts thereof are also useful for inhibiting the replication or infectivity of a virus.

The present invention further provides compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula (IV) or a pharmaceutically acceptable salt thereof, wherein:

R₂ is selected from the group consisting of -H, C_rC₁₂ straight chain alkyl, -CH,C₆H₅, -SiR₁₀R* .R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; Rg is selected from the group consisting of -H, -CH₃, and -CH₂CH₃;

R_n and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and p is an integer ranging from 6 to 8; with the proviso that the compound of Formula (IV) is not: cyclononylprodiginine, methylcyclooctylprodiginine, methylcyclodecylprodiginine, ethylcyclononylprodiginine, R39FF,

R39MF,

R39SF,

61 OFF, or

610MF. The compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (IV) or a pharmaceutically acceptable salt thereof are useful for treating or preventing cancer or neoplastic disease in a patient in need of such treatment or prevention. These compositions are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (IV) or a pharmaceutically acceptable salt thereof are useful for treating or preventing a viral infection in a patient in need of such treatment or prevention. These compositions are also useful for inhibiting the replication or infectivity of a virus.

The invention further provides methods for treating or preventing cancer or a neoplastic disease comprising administering to a patient in need of such treatment or prevention a composition comprising a therapeutically effective amount of a compound of Formula (IV) or a pharmaceutically acceptable salt thereof, wherein:

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_uR₁₂, -C(O)CH₃, -C(O) H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃;

R₁₀ is selected from the group consisting of C_rC₄ straight or branched chain alkyl and -C_CH₅;

R,, and R₁₂ are independently C_rC₃ straight or branched chain alkyl; and p is an integer ranging from 6 to 8.

The invention further provides methods for inhibiting the growth of a cancer cell or neoplastic cell comprising a contacting a cancer cell or neoplastic cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (IV) or a pharmaceutically acceptable salt thereof, wherein: R₂ is selected from the group consisting of -H, C_rC₁₂ straight chain alkyl,

-CH₂C₆H₅, -SiR₁₀RπR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₆ is selected from the group consisting of -H, -CH₃, and -CH,CH₃;

R_π and R₁₂ are independently C C₃ straight or branched chain alkyl; and p is an integer ranging from 6 to 8.

The invention further provides methods for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (IV) or a pharmaceutically acceptable salt thereof, wherein:

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R„R_I2, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃;

R,₀ is selected from the group consisting of C_rC₄ straight or branched chain alkyl, and -C₆H₅;

R_π and R_I2 are independently C,-C₃ straight or branched chain alkyl; and p is an integer ranging from 6 to 8. The invention further provides methods for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (IV) or a pharmaceutically acceptable salt thereof, wherein:

R₂ is selected from the group consisting of -H, C_rC₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R„R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R_β is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; R₁₀ is selected from the group consisting of C_rC₄ straight or branched chain alkyl and -C₆H₅;

R_n and R_I2 are independently C,-C₃ straight or branched chain alkyl; and p is an integer ranging from 6 to 8.

FORMULA V

The present invention provides methods for treating or preventing cancer or a neoplastic disease comprising administering to a patient in need of such treatment or prevention a composition comprising a therapeutically effective amount of a compound of Formula (V):

V

or a pharmaceutically acceptable salt thereof, wherein:

R_{ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₇ is selected from the group consisting of -H, C,-C₁₅ straight chain alkyl, -(CH₂)₉CH= H₂, -(CH₂)₆F, -(CH₂)₅OC₆H₅, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₆H₅, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)_uCOOH, -(CH₂)₁₂COOH, -(CH₂)₁₂OH, -(CH₂)₁₃OH, -(CH₂)_UCN, -(CH₂)_uOC(O)NH₂, -(CH₂)_n COOEt, -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, C₃-C₇ cycloalkyl, -C₆H₅, 2-pyrrolyl, -3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, and 3-furanyl, the phenyl being substituted with one or more halo, methyl, methoxyl, hydroxyl, methoxycarbonyl or trifluoromethyl groups;

R_g is selected from the group consisting of -H, C_rC_u straight chain alkyl, -(CH,)₄COOEt, and -C₆H₅; when R₇ is other than 2-pyrrolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pyrrolyl, then R_<, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R_I0 is selected from the group consisting of C_rC₄ straight or branched chain alkyl and -C₆H₅; R_π and R₁₂ are independently selected from the group consisting of -CH₃, -CH₂CH₃, and -C₃H₇;

R₁₆ is selected from the group consisting of -H, -CH₃, -CH₂CH₂CH₃, and -(CH₂)₆CH₃; and

R₁₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH; with the proviso that the compound of Formula (V) is not: prodigiosin, undecylprodigiosin, norprodigiosin, or nonylprodigiosin.

The present invention provides methods for inhibiting the growth of a cancer cell or neoplastic cell comprising a contacting a cancer cell or neoplastic cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (V) or a pharmaceutically acceptable salt thereof, wherein: R, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅,

-C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C_rC₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR.₀R* .R_I2, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; R₇ is selected from the group consisting of -H, C,-C,₅ straight chain alkyl, -(CH₂)₉CH=CH₂, -(CH₂)₆F, -(CH₂)₅OC₆H₅, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₆H₅, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂)₁₂COOH, -(CH₂)₁₂OH, -(CH₂)₁₃OH, -(CH₂)_πCN, -(CH₂)_nOC(O)NH₂, -(CH₂)„COOEt, -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, C₃-C₇ cycloalkyl, -C₆H₅, 2-pynolyl, -3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, and 3-furanyl, the phenyl being substituted with one or more halo, methyl, methoxyl, hydroxyl, methoxycarbonyl or trifluoromethyl groups;

R_g is selected from the group consisting of -H, Cj-C,, straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pyrrolyl, R, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃; R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R, i and R₁₂ are independently selected from the group consisting of -CH₃, -CH₂CH₃, and -C₃H₇;

R_I6 is selected from the group consisting of -H, -CH₃, -CH₂CH₂CH₃, and -(CH₂)₆CH₃; and

R_I7 is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH; with the proviso that the compound of Formula (V) is not: prodigiosin, undecylprodigiosin, norprodigiosin, or nonylprodigiosin.

The present invention provides methods for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (V) or a pharmaceutically acceptable salt thereof, wherein:

R- is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR_I0R_nR.₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₇ is selected from the group consisting of -H, C_rC₁₅ straight chain alkyl, -(CH₂)₉CH=CH₂, -(CH₂)₆F, -(CH₂)₅OC₆H₅, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₆H₅, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)_nCOOH, -(CH₂)₁₂COOH, -(CH₂)₁₂OH, -(CH₂)₁₃OH, -(CH₂)„CN, -(CH₂)_uOC(O)NH₂, -(CH₂)_nCOOEt, -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, C₃-C₇ cycloalkyl, -C₆H₅, 2-pynolyl, -3-pynolyl, 2-pyridyl, 3-ρyridyl, 4-pyridyl, 2-furanyl, and 3-furanyl, the phenyl being substituted with one or more halo, methyl, methoxyl, hydroxyl, methoxycarbonyl or trifluoromethyl groups;

R_g is selected from the group consisting of -H, C,-C_n straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pyrrolyl, Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pyrrolyl, then Rt, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R₁₀ is selected from the group consisting of C_j- straight or branched chain alkyl and -C₆H₅; R_n and R₁₂ are independently selected from the group consisting of -CH₃, -CH₂CH₃, and -C₃H₇;

R₁₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH.

The present invention provides methods for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (V) or a pharmaceutically acceptable salt thereof, wherein:

R_t is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R..R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; R₇ is selected from the group consisting of -H, C,-C₁₅ straight chain alkyl, -(CH₂)₉CH-CH₂, -(CH₂)₆F, -(CH₂)₅OC₆H₅, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₆H₅, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂)₁₂COOH, -(CH₂)_I2OH, -(CH₂)₁₃OH, -(CH₂)_πCN, -(CH₂)_πOC(O)NH₂, -(CH₂)_π COOEt, -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, C₃-C₇ cycloalkyl, -C₆H₅, 2-pynolyl, -3-pynolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, and 3-furanyl, the phenyl being substituted with one or more halo, methyl, methoxyl, hydroxyl, methoxycarbonyl or trifluoromethyl groups;

R₈ is selected from the group consisting of -H, C_rC_u straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, R, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃; io is selected from the group consisting of C_r-C₄ straight or branched chain alkyl and -C₆H₅;

R_u and R₁₂ are independently selected from the group consisting of -CH₃, -CH₂CH₃, and -C₃H₇;

The present invention may be understood more fully by reference to the following figures, schemes, detailed description and illustrative examples which are intended to exemplify non-limiting embodiments of the invention.

3.1. DEFINITIONS AND ABBREVIATIONS

Examples of C,-C₃ straight or branched chain alkyl groups include but are not limited to methyl, ethyl, 1-propyl, and 2-propyl.

Examples of C,-C₄ straight or branched chain alkyl groups include but are not limited to methyl, ethyl, 1-propyl, 2-propyl, 1 -butyl, 2-butyl, 2-methyl-l-propyl, and 2- methyl-2-propyl. Examples of C_rC₆ straight or branched chain alkyl groups include but are not limited to methyl, ethyl, 1-propyl, 2-propyl, 1 -butyl, 2-butyl, 2-methyl-l-propyl, 2-methyl-2-propyl, 1-pentyl, 2-pentyl, 3-pentyl, 2-methyl- 1 -butyl, 3-methyl-l -butyl, 2-methyl-3 -butyl, 2,2-dimethyl- 1-propyl, 1-hexyl, 2-hexyl, 3-hexyl, 2-methyl- 1-pentyl, 3 -methyl- 1-pentyl, 4-methyl- 1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl,

4-methyl-2-pentyl, 2,2-dimethyl- 1 -butyl, 3, 3 -dimethyl-1 -butyl, and 2-ethyl-l -butyl.

Examples of C,-C₆ straight chain alkyl groups include but are not limited to methyl, ethyl, 1-propyl, 1 -butyl, 1-pentyl, and 1-hexyl.

Examples of C_rC₁₀ straight chain alkyl groups include but are not limited to methyl, ethyl, 1-propyl, 1 -butyl, 1-pentyl, 1-hexyl, 1-heptyl, 1 -octyl, 1-nonyl, and 1-decyl. Examples of C₅-C₁₀ straight chain alkyl groups include but are not limited to 1-pentyl, 1-hexyl, 1-heptyl, 1 -octyl, 1-nonyl, and 1-decyl.

Examples of C[-C_u straight chain alkyl groups include but are not limited to methyl, ethyl, 1-propyl, 1-butyl, 1-pentyl, 1-hexyl, 1-heptyl, 1-octyl, 1-nonyl, 1-decyl, and 1-undecyl.

Examples of C₆-C, , straight chain alkyl groups include but are not limited to 1-hexyl, 1-heptyl, 1-octyl, 1-nonyl, 1-decyl, and 1-undecyl.

Examples of C_rC₁₂ straight chain alkyl groups include but are not limited to methyl, ethyl, 1-propyl, 1-butyl, 1-pentyl, 1-hexyl, 1-heptyl, 1-octyl, 1-nonyl, 1-decyl, 1-undecyl, and 1-dodecyl.

Examples of C₃-C₁₂ straight chain alkyl groups include but are not limited to 1-propyl, 1-butyl, 1-pentyl, 1-hexyl, 1-heptyl, 1-octyl, 1-nonyl, 1-decyl, 1-undecyl, - 1-dodecyl.

Examples of C,-C₁₅ straight chain alkyl groups include, but are not limited to methyl, ethyl, 1-propyl, 1-butyl, 1-pentyl, 1-hexyl, 1-heptyl, 1-octyl, 1-nonyl, 1-decyl, 1-undecyl, 1-dodecyl, 1-tridecyl, 1-tetradecyl, and 1-pentadecyl.

Examples of C₃-C₁₅ straight chain alkyl groups include but are not limited to 1-propyl, 1-butyl, 1-pentyl, 1-hexyl, 1-heptyl, 1-octyl, 1-nonyl, 1-decyl, 1-undecyl, 1-dodecyl, 1-tridecyl, 1-tetradecyl, and 1-pentadecyl. Examples of C₈-C₁₅ straight chain alkyl groups include but are not limited to 1 -octyl,

1-nonyl, 1-decyl, 1-undecyl, 1-dodecyl, 1-tridecyl, 1-tetradecyl, and 1-pentadecyl.

Examples of C^ -G, straight chain alkyl groups include but are not limited to (methyl)-C(O)-, (ethyl)-C(O)-, (l-propyl)-C(O)-, (l-butyl)-C(O)-, (l-pentyl)-C(O)-, (l-hexyl)-C(O)-, (l-heptyl)-C(O)-, (l-octyl)-C(O)-, and (l-nonyl)-C(O)-. Examples of CH(OH)C_[-C₉ straight chain alkyl groups include but are not limited to CH(OH)-(methyl), CH(OH)-(ethyl), CH(OH)-( 1-propyl), CH(OH)-( 1-butyl), CH(OH)-(l-pentyl), CH(OH)-( 1-hexyl), CH(OH)-( 1-heptyl), CH(OH)-(l-octyl), and CH(OH)-(l-nonyl). Examples of CH(Cl)C_rC₉ straight chain alkyl groups include but are not limited to

CH(Cl)-(methyl), CH(Cl)-(ethyl), CH(Cl)-( 1-propyl), CH(Cl)-( 1-butyl), CH(Cl)-( 1-pentyl), CH(Cl)-(l-hexyl), CH(Cl)-( 1-heptyl), CH(Cl)-( 1-octyl), and CH(Cl)-(l-nonyl).

Examples of C₃-C₇ cycloalkyl groups include but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl. As used herein, unless defined otherwise, the abbreviation (BOC) denotes

-C(O)OC(CH₃)₃, (Cbz) denotes C(O)OCH₂C₆H₅, (THP) denotes -2-tetrahydropyranyl, (MOM) denotes -OCH₂OCH₃, and (TROC) denotes -C(O)OCH₂C(Cl)₃.

It is to be understood that the R₅ group of the compounds of Formula H and Formula in can be attached to any carbon atom of the five to ten membered ring to which R₅ is attached.

The structures of compounds R39FF, R39MF, R39SF, 61 OFF and 610MF are disclosed at page 925 of Gerber et al, 1973, J. Heterocycl. Chem. 10:925-9 and in Table 1.

TABLE 1

Compound R39FF: R=-CH(CH₂)₇- CH₃

15 Compound 61 OFF: R= -CH(CH₂)₈- CH₂CH₃

Compound R39MF: R=-(CH₂)₈C(0)-

Compound R39SF: R=-CH(OH)(CH₂)₈-

20

Compounds 610MF: R= -CHC(X)(CH₂)₇C(Y)-

CH₃

25 (X = O and Y = HOH) and (X = HOH and Y = O)

30

35 In certain instances, the compounds of the invention are known by more than one name. The following Table 2 indicates synonyms of compounds described herein.

When administered to a patient, e.g., a mammal for veterinary use or a human for clinical use, the Pynole-Type compounds are administered in isolated form. As used herein, "isolated" means that the Pynole-Type compounds are separated from other components of either (a) a natural source, such as a plant or cell, preferably bacterial culture, or (b) a synthetic organic chemical reaction mixture. Preferably, via conventional techniques, the Pynole-Type compounds are purified. As used herein, "purified" means that when isolated, the isolate contains at least 95%, preferably at least 98%, of a single Pynole-Type compound by weight of the isolate.

4. DETAILED DESCRIPTION OF THE INVENTION

4.1. FORMULA I

The present invention encompasses novel compounds having the general Formula (I):

and pharmaceutically acceptable salts thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃,

-CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_πR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; R₃ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl,

-CH(R₁₄)(R₁₅) wherein R₁₄ and R₁₅ are independently 0,-0,₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the - CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups; R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R,, and R₁₂ are independently C,-C₃ straight or branched chain alkyl;

R,₆ and R,₇ is -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: butyl-meta-cycloheptylprodiginine, metacycloprodigiosin,

4-ethoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi-lH-pynole, or 4-propoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi-lH-pynole.

Where R₃ of the compounds of Formula (I) is a -CH₂C₆H₅ group substituted with one cyano or one or more halo, methoxyl or trifluoromethyl groups, R₃ is preferably 4-chlorobenzyl, -2-methoxybenzyl, -3-methoxybenzyl, -4-methoxybenzyl, 2,4-dichlorobenzyl, 2,4-difluorobenzyl, 4-cyanobenzyl, or 4-trifluoromethylbenzyl.

A prefened subclass of the compounds of Formula (I) is that wherein: each R, is independently selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, (l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl;

R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: butyl-meta-cycloheptylprodiginine, metacycloprodigiosin,

4-ethoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi-lH-pynole, or 4-propoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi-lH-pynole. A second prefened subclass of the compounds of Formula (I) is that wherein: each R, is -H;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, n-C*-C₁₀ alkyl and -CH₂C₆H₅;

4-ethoxy-5 -((3,5 -nonamethylene-2H-pynol-2 -ylidene)m ethyl) -2 , 2 '-bi- 1 H-pynole, or 4-propoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi-lH-pynole.

A third prefened subclass of the compounds of Formula (I) is that wherein: each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl;

R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that when m is 3, R₃ is not -CH₂CH₃ and when m is 1, R₃ is not -(CH₂)₃CH₃. A fourth prefened subclass of the compounds of Formula (I) is that wherein: each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, -CH₃, -«-C₃H₇, -t-C₃H₇, C₅-C,₀ straight chain alkyl, (l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl;

R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5.

A fifth prefened subclass of the compounds of Formula (I) are those wherein: each R, is independently selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C_I0 straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl;

R_I6 and R₁₇ are -H; and m is 2, 4, or 5. In one embodiment, prefened compounds of Formula (I) are selected from the group consisting of:

2-Ethyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1 ]dodeca-9(12),l 1-diene; 5 l l-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1 ]dodeca-9(12),l 1-diene;

2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-n-Propyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Pentyl-ll-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Benzyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

15 (S)-2-R-Pentyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl ))-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-«-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl ))-10-azabicyclo[7.2.1]dodeca-9(12),ll-diene;

(S)-2-«-Butyl-ll-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-

20 ylidene)methyl ))-10-azabicyclo[7.2.1]dodeca-9(12),ll-diene;

(R)-2-/ι-Butyl- 1 l-((3-methoxy-5-(lH-pynOl-2-yl)-2H-pynoI-2- ylidene)methyl ))-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pyrrol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

25 (R)-2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl ))-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

(S)-2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pyrrol-2- ylidene)methyl ))-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-

30 ylidene)methyl ))-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

(S)-2-n-Propyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl ))-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

(R)-2-«-Propyl- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl ))- 10-azabicyclo[7.2.1 ]dodeca-9(l 2), 11 -diene;

35 2-Methyl- 12-((3-methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-Ethyl- 12-((3 -methqxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 11 - azabicyclo[8.2.1jtrideca-10(13),12-diene; 2-n-Proρyl- 12-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-n-Butyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-«-Pentyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

12-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 11 - azabicyclo[8.2.1]trideca-10(13),12-diene;

2-Methyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene; 13-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Ethyl- 12-methyl- 13-((3-methoxy-5-(l -methyl- lH-pynol-2-yl)-2H-pynol- 2-ylidene)methyl)- 12-azabicyclo[9.2.1 jtetradeca- 11(14), 13-diene;

2-Ethyl- 12-methyl- 13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-«-Propyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-«-Butyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene; 14-((3 -Methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 13- azabicyclo[10.2.1]pentadeca-12(15),14-diene;

2-Butyl-l l-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9( 12), 11 -diene;

2-Butyl-l l-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-methyl-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- methyl- 10-azabicyclo[7.2.1]dodeca-9(l 2), 11-diene;

2-Ethyl- 11 -((3-benzyloxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-

10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 2-Butyl- 11 -((3 -hydroxy-5-( lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- 10- azabicyclo[7.2. l]dodeca-9(l 2), 11-diene;

2-Butyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(l 2), 11-diene; 5 l l-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-ll-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Propyl- 11 -((3 -benzyloxy-5-( lH-pynol-2-yl)-2H-pynol-2- 10 ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Η-Pentyl- 11 -((3 -benzyloxy-5-( lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Benzyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 15 2-Methyl-14-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

13-azabicyclo[10.2.1]pentadeca-12(15),14-diene;

15-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-14- azabicyclof 11.2.1 ]pentadeca- 13(16), 15-diene;

2-Methyl-15-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 20 14-azabicyclo[11.2.1]pentadeca-13(16),15-diene;

2-(2-Ηydroxy-«-butyl)-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(l 2), 11 -diene;

2-(2-Chloro-n-butyl)-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 25 2-Butyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2. l]dodeca-9(12), 11-diene;

11 -((3-Ethoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2. l]dodeca-9(12), 11-diene;

2-Methyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- 30 azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Propyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pyrrol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-7j-Pentyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 35 2-Benzyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Ethyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; . 2-Methyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

13-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2.1 jtetradeca- 11(14), 13-diene;

2-Ethyl- 12-methyl- 13-((3-benzyloxy-5-(l -methyl- lH-pynol-2-yl)-2H-pynol- 2-ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Ethyl- 12-methyl- 13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-ll(14),13-diene;

2-«-Propyl- 13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ^' ylidene)methyl)- 12-azabicyclo[9.2.1 Jtetradeca- 11(14), 13-diene; and 2-n-Butyl- 13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2. l]tetradeca-l l(14),13-diene or a pharmaceutically acceptable salt thereof.

The present invention provides compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -Η, -CΗ₃, -CH₂CH₃,

-CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R..R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; R₃ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl,

-CH(R₁₄)(R_I5) wherein R₁₄ and R₁₅ are independently C,-C₁₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups;

R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R,, and R₁₂ are independently C,-C₃ straight or branched chain alkyl; R₁₆ and R,₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: butyl-meta-cycloheptylprodiginine, metacycloprodigiosin,

The compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (I) or a pharmaceutically acceptable salt thereof are useful for treating or preventing cancer or neoplastic disease in a patient in need of such treatment or prevention. These compositions are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (I) or a pharmaceutically acceptable salt thereof are useful for treating or preventing a viral infection in a patient in need of such treatment or prevention. These compositions are also useful for inhibiting the replication or infectivity of a virus.

A prefened subclass of the compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (I) or a pharmaceutically acceptable salt thereof is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃ and -CH₂C₆H_S;

4-ethoxy-5-((3 ,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi- 1 H-pynole, or 4-propoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi-lH-pynole.

A second prefened subclass of the compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (I) or a pharmaceutically acceptable salt thereof are those wherein, in the compound of Formula (I): each R, is -H;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C_I0 straight chain alkyl, and -CH₂C₆H₅; R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: butyl-meta-cycloheptylprodiginine, metacycloprodigiosin, 4-ethoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi-l H-pynole, or 4-propoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi- 1 H-pynole.

A third prefened subclass of the compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (I) or a pharmaceutically acceptable salt thereof is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R,₆ and R_I7 are -H; and m is an integer ranging from 1 to 5; with the proviso that when m is 3, R₃ is not -CH₂CH₃ and when m is 1, R₃ is not -(CH₂)₃CH₃.

A fourth prefened subclass of the compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (I) or a pharmaceutically acceptable salt thereof are those wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, -CH₃, -n-C₃H₇, -z-C₃H₇, C₅-C₁₀ straight chain alkyl, (l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl;

R,₆ and R,₇ are -H; and m is an integer ranging from 1 to 5.

A fifth prefened subclass of the compositions comprising a pharmaceutically acceptable carrier and a compound of Formula I) or a pharmaceutically acceptable salt thereof is that, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R₁₆ and R_I7 are -H; and m is 2, 4, or 5.

In one embodiment, prefened compounds of Formula (I) are selected from the group consisting of:

2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- 5 azabicyclo[7.2.1]dodeca-9(12),l 1-diene; l l-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 10 2-«-Propyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(l 2), 11-diene;

2-Benzyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 15 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-«-Pentyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-n-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2. l]dodeca-9(12), 11-diene; 20 (S)-2-n-Butyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-n-Butyl- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 25 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2. l]dodeca-9(l 2), 11 -diene;

(S)-2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)m ethyl)- 10-azabicyclo[7.2.1 ]dodeca-9( 12), 11 -diene; 30 (R)-2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-«-Propyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-«-Propyl- 11 -((3-methoxy-5-( lH-pynol-2-yl)-2H-pynol-2- 35 ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 2-Methyl- 12-((3 -methoxy-5-( lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-Ethyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)-ll- azabicyclo[8.2.1 jtrideca- 10(13), 12-diene; 2-rc-Propyl- 12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- ll-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-o-Butyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l -azabicyclo[8.2.1]trideca-10(13),12-diene;

2-n-Pentyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- 1 l-azabicyclo[8.2.1]trideca-10(13),12-diene;

12-((3-Methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 11 - azabicyclo[8.2.1]trideca-10(13),12-diene;

2-Methyl-13-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene; 13-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Ethyl-12-methyl-13-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- 2-ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Ethyl-12-methyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-ll(14),13-diene;

2-«-Butyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene; 14-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-13- azabicyclo[10.2.1]pentadeca-12(15),14-diene;

2-Butyl-l l-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2. l]dodeca-9(12), 11-diene;

2-Butyl-l l-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-methyl-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

2-Butyl- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- methyl-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Ethyl- 11 -((3 -benzyloxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 2-Butyl-ll-((3-hydroxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 5 l l-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Propyl- 11 -((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- 10 ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Pentyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(l 2), 11 -diene;

2-Benzyl-ll-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),ll-diene; 15 2-Methyl-14-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

13-azabicyclo[10.2.1]pentadeca-12(15),14-diene;

15-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-14- azabicyclo[11.2.1]pentadeca-13(16),15-diene;

2-Methyl-15-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 20 14-azabicyclo[l 1.2.1]pentadeca-13(16),15-diene;

2-(2-Ηydroxy-n-butyl)-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(l 2), 11 -diene;

2-(2-Chloro-«-butyl)-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene; 25 2-Butyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2. l]dodeca-9(12),l 1-diene; l l-((3-Ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2. l]dodeca-9(l 2), 11-diene;

2-Methyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- 30 azabicyclo[7.2.1]dodeca-9(12),ll-diene;

2-rt-Propyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Pentyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 35 2-Benzyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2. l]dodeca-9(12), 11-diene;

2-Ethyl- 11 -((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 2-Methyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2.1 Jtetradeca- 11(14), 13-diene;

13-((3-Benzyloxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2.1 Jtetradeca- 11 (14), 13-diene;

2-Ethyl- 12-methyl- 13 -((3 -benzyloxy-5 -( 1 -methyl- lH-pynol-2-yl)-2H-pynol- 2-ylidene)methyl)- 12-azabicyclo[9.2. ljtetradeca- 11 ( 14), 13 -diene;

2-Ethyl-12-methyl-13-((3-benzyloxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)- 12-azabicyclo[9.2.1 Jtetradeca- 11(14), 13-diene;

2-«-Propyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 12-azabicyclo [9.2.1 J tetradeca- 11 ( 14), 13 -diene; and 2-«-Butyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2.1 Jtetradeca- 11(14), 13-diene or a pharmaceutically acceptable salt thereof.

The invention further provides methods for treating or preventing cancer or neoplastic disease in a patient comprising administering to a patient in need of such treatment or prevention a composition comprising a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -Η, -CΗ₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR,oR_uR,₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₃ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH(R,₄)(R,₅) wherein R,₄ and R,₅ are independently C,-C,₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the

R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅; R, , and R₁₂ are independently C,-C₃ straight or branched chain alkyl; m is an integer ranging from 1 to 5; and when m is 3 and R₂ is -CH₂CH₃, then R,₆ is -H or -CH₃ and R₁₇ is -H; when m is 3 and R₂ is -CH₃, then R₁₆ is -H or -CH₃ and R₁₇ is -H or -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R₁₆ and R₁₇ are -H only; with the proviso that the compound of Formula (I) is not: metacycloprodigiosin.

A prefened compound for use in the methods for treating or preventing cancer or neoplastic disease is butyl-meta-cycloheptylprodiginine or a pharmaceutically acceptable salt thereof.

Other prefened compounds for use in the methods for treating or preventing cancer or neoplastic disease are selected from the group consisting of:

2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 1 l-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2. lJdodeca-9(12),l 1-diene;

2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

2-w-Propyl- 11 -((3-methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

2-n-Pentyl- 11 -((3 -methoxy-5-( 1 H-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Benzyl- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene; (S)-2-«-Pentyl-l 1 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l 0-azabicyclo[7.2.1 Jdodeca-9( 12), 11 -diene;

(R)-2-n-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(l 2), 11 -diene;

(S)-2-/2-Butyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

(R)-2-7i-Butyl-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene; (R)-2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 Jdodeca-9(12), 11 -diene;

(S)-2-Methyl- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo [7.2.1 Jdodeca-9(l 2), 11 -diene; (R)-2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-«-Propyl-l 1 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 Jdodeca-9(l 2), 11 -diene;

(R)-2-«-Propyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1Jtrideca-10(13),12-diene;

2-Ethyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-l l- azabicyclo[8.2.1]trideca-10(13),12-diene; 2-n-Propyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1Jtrideca-10(13),12-diene;

2-/2-Butyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1Jtrideca-10(13),12-diene;

2-π-Pentyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 1 l-azabicyclo[8.2.1Jtrideca-10(13),12-diene;

12-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-l l- azabicyclo[8.2.1Jtrideca-10(13),12-diene;

2-Methyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1Jtetradeca-l l(14),13-diene; 13-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2.1 ]tetradeca-l 1 (14), 13-diene;

2-Ethyl-12-methyl-13-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- 2-ylidene)methyl)- 12-azabicyclo[9.2.1 Jtetradeca- 11 ( 14), 13 -diene;

2-Ethyl- 12-methyl- 13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 12-azabicyclo[9.2.1 ]tetradeca-l 1(14), 13-diene;

2-«-Butyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene; 14-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 13- azabicyclo[10.2.1Jpentadeca-12(15),14-diene;

2-Butyl- 11 -((3 -methoxy-5-( 1 -methyl- lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(l 2), 11 -diene; 2-Butyl-l l-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-methyl-l 0-azabicyclo[7.2.1 ]dodeca-9(l 2), 11 -diene;

2-Butyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- methyl-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Ethyl- 11 -((3-benzyloxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10 10-azabicyclo[7.2.1]dodeca-9(12),ll-diene;

2-Butyl-l l-((3-hydroxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 15 l l-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

2-Methyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

2-n-Propyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- 20 ylidene)methyl)-10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

2-n-Pentyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

2-Benzyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 25 2-Methyl-14-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

13-azabicyclo[10.2.1]pentadeca-12(15),14-diene;

15-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-14- azabicyclof 11.2.1 Jpentadeca- 13(16), 15-diene;

2-Methyl-15-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 30 14-azabicyclo[l 1.2.1]pentadeca-13(16),15-diene;

2-(2-Ηydroxy-«-butyl)- 11 -((3-methoxy-5-( lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-(2-Chloro-7z-butyl)-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 35 2-Butyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

11 -((3 -Ethoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 5 2-Methyl- 11 -((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

2-«-Proρyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12).l 1-diene;

2-«-Pentyl-l l-((3-ethoxy-5-(lH-pynol-2-yI)-2H-pynol-2-ylidene)methyl)- 10 10-azabicyclo[7.2.1]dodeca-9(12),ll-diene;

2-Benzyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Ethyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 15 2-Methyl- 13 -((3-benzyloxy-5 -( lH~pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2.1]tetradeca-ll(14),13-diene;

13-((3-Benzyloxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2.1 Jtetradeca- 1 l(14),13-diene;

2-Ethyl- 12-methyl- 13-((3-benzyloxy-5-( 1 -methyl- lH-pynol-2-yl)-2H-pynol- 20 2-ylidene)methyl)- 12-azabicyclo [9.2.1 Jtetradeca- 11 ( 14), 13 -diene;

2-Ethyl-12-methyl-13-((3-benzyloxy-5-(lH-ρynol-2-yl)-2H-ρynol-2- ylidene)methyl)- 12-azabicyclo[9.2.1 Jtetradeca- 11(14), 13-diene;

2-n-Propyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l 2-azabicyclo[9.2.1 Jtetradeca- 11(14), 13-diene; and 25 2-n-Butyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2.1Jtetradeca-l l(14),13-diene or a pharmaceutically acceptable salt thereof.

For use in the methods for treating or preventing cancer or neoplastic disease, a prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): 30 each R* is independently selected from the group consisting of -Η, -CΗ₃, -CH₂CH₃,

-CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_uR,₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; 35 R₃ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH(R,₄)(R₁₅) wherein R₁₄ and R₁₅ are independently C,-C₁₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups;

R,₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R,, and R₁₂ are independently C C₃ straight or branched chain alkyl; and R₁₆ and R,₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: metacycloprodigiosin.

For use in the methods for treating or preventing cancer or neoplastic disease, a second prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: metacycloprodigiosin. For use in the methods for treating or preventing cancer or neoplastic disease, a third prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R. is -H;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, and

-CH₂C₆H₅;

R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: metacycloprodigiosin. For use in the methods for treating or preventing cancer or neoplastic disease, a fourth prefened subclass of the compounds of Formula (I) is that wherein, in the compounds of Formula (I): each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅;

R_I6 and R_I7 are -H; and m is an integer ranging from 1 to 5; with the proviso that when m is 3, R₃ is not -CH₂CH₃ and when m is 1, R₃ is not -(CH₂)₃CH₃.

For use in the present methods for treating or preventing cancer or neoplastic disease, a fifth prefened subclass of the compounds of Formula (I) is that wherein, in the compounds of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, (l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl;

R,₆ and R,₇ are -H; and m is an integer ranging from 1 to 5.

For use in the present methods for treating or preventing cancer or neoplastic disease, a sixth prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃ and^'-CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C_I0 straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl), and (l-chloro)butyl;

R,₆ and R,₇ are -H; and m is 2, 4, or 5. For use in the present methods for treating or preventing cancer or neoplastic disease, a seventh prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, -(CH₂)₂CH₃, and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydxoxy)butyl, and (l-chloro)butyl; m is an integer ranging from 1 to 5; when m is 3 and R₂is -CH₃, then R,₆is selected from the group consisting of -H and -CH₃ and R₁₇ is selected from the group consisting of -H and -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R,₆ and R,₇ are -H only; and with the proviso that the compound of Formula (I) is not: metacycloprodigiosin. The invention further provides methods for inhibiting the growth of a cancer cell or neoplastic cell comprising a contacting a cancer cell or neoplastic cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (I) or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃,

-CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR,₀R_πR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; R₃ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl,

-CH(R₁₄)(R₁₅) wherein R₁₄ and R,₅ are independently C,-C,₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups;

R_I0 is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R,, and R₁₂ are independently C,-C₃ straight or branched chain alkyl; m is an integer ranging from 1 to 5; when m is 3 and R₂ is -CH₂CH₃, then R₁₆ is -H or -CH₃ and R,₇ is -H; when m is 3 and R₂ is -CH₃, then R₁₆ is -H or -CH₃ and R,₇ is -H or -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R₁₆ and R₁₇ are -H only; with the^'proviso that the compound of Formula (I) is not: metacycloprodigiosin. A prefened compound for use in the method is butyl-meta-cycloheptylprodiginine or a pharmaceutically acceptable salt thereof.

Other prefened compounds for use in the method are selected from the group consisting of: 5 2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)-10- azabicyclo[7.2.1Jdodeca-9(12),l 1-diene; l l-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2. lJdodeca-9(12),l 1-diene;

2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10 10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

2-π-Propyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene; 15 2-Benzyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

10-azabicyclo[7.2.1]dodeca-9(12),ll-diene;

(S)-2-n-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

(R)-2-/z-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- 20 ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(5)-2-«-Butyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

(R)-2-n-Butyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9( 12), 11 -diene; 25 (S)-2-Ethyl-l 1 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

10-azabicyclo[7.2. lJdodeca-9(12),l 1-diene;

(R)-2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 Jdodeca-9( 12), 11 -diene;

(S)-2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- 30 ylidene)methyl)-10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

(R)-2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-«-Propyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l 0-azabicyclo[7.2. l]dodeca-9(12),l 1-diene; 35 (R)-2-n-Propyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

2-Methyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1Jtrideca-10(13),12-diene; 2-Ethyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-l l- azabicyclo[8.2.1Jtrideca-10(13),12-diene;

2-n-Proρyl-12-((3-methoxy-5-(lH-ρynol-2-yl)-2H-ρynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1Jtrideca-10(13),12-diene;

2-«-Butyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-«-Pentyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- ll-azabicyclo[8.2.1]trideca-10(13),12-diene;

12-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-l l- azabicyclo[8.2.1]trideca-10(13),12-diene; 2-Methyl-l 3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2.1]tetradeca-ll(14),13-diene;

13-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2.1]tetradeca-ll(14),13-diene;

2-Ethyl-12-methyl-13-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- 2-ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-ll(14),13-diene;

2-Ethyl-12-methyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 12-azabicyclo[9.2.1 ]tetradeca-l 1(14), 13-diene;

2-«-Proρyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2. ljtetradeca- 11 (14), 13-diene; 2-«-Butyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

14-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-13- azabicyclo[ 10.2.1 ]pentadeca- 12(15), 14-diene;

2-Butyl-l l-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl- 11 -((3-methoxy-5-(l -methyl- lH-pynol-2-yl)-2H-ρynol-2- ylidene)methyl)-10-methyl-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- methyl-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 2-Ethyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

5 2-Butyl- 11 -((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

10-azabicyclo[7.2.1]dodeca-9(12),ll-diene;

11 -((3 -Benzyloxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-ll-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-n-Propyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-n-Pentyl-ll-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene; 15 2-Benzyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-14-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 13-azabicyclo[10.2.1]pentadeca-12(15),14-diene;

15-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-14- 0 azabicyclo[11.2.1]pentadeca-13(16),15-diene;

2-Methyl-15-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 14-azabicyclo[11.2.1]pentadeca-13(16),15-diene;

2-(2-Ηydroxy-«-butyl)-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene; 25 2-(2-Chloro-R-butyl)-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(l 2), 11-diene;

2-Butyl- 11 -((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

11 -((3 -Ethoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- 30 azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl- 11 -((3-ethoxy-5-(lH-pynol-2-yl)-2H-ρynol.-2-ylidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-π-Propyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 35 2-n-Pentyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Benzyl- 11 -((3-ethoxy-5 -( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2. l]dodeca-9(12),l 1-diene; 2-Ethyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1 ]dodeca-9(l 2), 11-diene;

2-Methyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

13-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Ethyl- 12-methyl- 13 -((3-benzyloxy-5-(l -methyl- lH-ρynol-2-yl)-2H-pynol- 2-ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Ethyl-12-methyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 12-azabicyclo[9.2.1 ]tetradeca- 11(14), 13-diene; 2-n-Propyl- 13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene; and

2-«-Butyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene or a pharmaceutically acceptable salt thereof. For use in the methods for inhibiting the growth of a cancer or neoplastic cell, a second prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -Η, -CΗ₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃) , -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R„R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₃ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH(R,₄)(R,₅) wherein R₁₄ and R,₅ are independently C,-C,₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-ρyridyl)methyI, and -CH₂C₆H₅, the

R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅; R. , and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and R₁₆ and R_I7 are -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: metacycloprodigiosin. For use in the methods for inhibiting the growth of a cancer or neoplastic cell, a third prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl,

(l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: metacycloprodigiosin. For use in the methods for inhibiting the growth of a cancer or neoplastic cell, a fourth prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is -H;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, and

-CH₂C₆H₅;

R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: metacycloprodigiosin.

For use in the methods for inhibiting the growth of a cancer or neoplastic cell, a fifth prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl;

R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that when m is 3, R₃ is not -CH₂CH₃ and when m is 1, R₃ is not -(CH₂)₃CH₃.

For use in the methods for inhibiting the growth of a cancer or neoplastic cell, a sixth prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, (l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R₁₆ and R,₇ are -H; and m is an integer ranging from 1 to 5.

For use in the methods for inhibiting the growth of a cancer or neoplastic cell, a seventh prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅;

R₁₆ and R₁₇ are -H; and _m is 2, 4, or 5.

For use in the methods for inhibiting the growth of a cancer or neoplastic cell, an eighth prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, -(CH₂)₂CH₃, and

-CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydxoxy)butyl, and (l-chloro)butyl; m is an integer ranging from 1 to 5; when m is 3 and R₂ is -CH₃, then R_[6 is selected from the group consisting of -H and

-CH₃ and R₁₇is selected from the group consisting of -H and -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R₁₆ and R_I7 are -H only; and with the proviso that the compound of Formula (I) is not: metacycloprodigiosin. The invention further provides methods for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (I): each R- is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_uR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₃ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH(R,₄)(R₁₅) wherein R,₄ and R₁₅ are independently C,-C,₂ straight chain alkyl, -C(O)C_r C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups;

R,, and R₁₂ are independently C,-C₃ straight or branched chain alkyl; m is an integer ranging from 1 to 5; and when m is 3 and R₂ is -CH₂CH₃, then R₁₆ is -H or -CH₃ and R,₇ is -H; when m is 3 and R₂ is -CH₃, then R₁₆ is -H or -CH₃ and R,₇ is -H or -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R,₆ and R₁₇ are -H only. A prefened compound for use in the methods for treating or preventing a viral infection is butyl-meta-cycloheptylprodiginine or a pharmaceutically acceptable salt thereof. Another prefened compound for use in the method for treating or preventing a viral infection is metacycloprodigiosine or a pharmaceutically acceptable salt thereof.

Other prefened compounds for use in the method are selected from the group consisting of:

2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; l l-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-n-Propyl-ll-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 2-n-Pentyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Benzyl-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-«-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(l 2), 11 -diene;

(R)-2-«-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2. l]dodeca-9(l 2), 11 -diene;

(S)-2-n-Butyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; (R)-2-«-Butyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-Methyl-l 1 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(l 2), 11 -diene;

(R)-2-Methyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; (S)-2-«-Propyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-«-Propyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pyrrol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 1 l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-Ethyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-ll- azabicyclo[8.2.1]trideca-10(13),12-diene;

2-n-Proρyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- ll-azabicyclo[8.2.1]trideca-10(13),12-diene; 2-n-Butyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-7z-Pentyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 1 l-azabicyclo[8.2.1]trideca-10(13),12-diene; 12-((3-Methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-l l- azabicyclo[8.2.1]trideca-10(13),12-diene;

2-Methyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

13 -((3-Methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12- azabicyclo[9.2.1]tetradeca-l 1(14), 13-diene;

2-Ethyl- 12-methyl-l 3-((3-methoxy-5-(l -methyl- lH-pynol-2-yl)-2H-pynol- 2-ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Ethyl-12-methyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-ll(14),13-diene; 2-n-Propyl- 13-((3-methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-«-Butyl-13-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

14-((3 -Methoxy-5-( lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 13 - azabicyclo[10.2.1]pentadeca-12(15),14-diene;

2-Butyl- 11 -((3-methoxy-5-(l -methyl-lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl- 11 -((3 -methoxy-5-(l -methyl- lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-methyl- 10-azabicyclo[7.2.1 ]dodeca-9(12), 11 -diene; 2-Butyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)-10- methyl-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Ethyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),ll-diene;

2-Butyl-l l-((3-hydroxy-5-(lH-pynol-2-yl)-2H-pyrrol-2-ylidene)methyl)-10- azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

2-Butyl-l l-((3-benzyloxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l L-diene; l l-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 2-Methyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-n-Propyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 2-n-Pentyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo [7.2.1 ]dodeca-9( 12), 11 -diene;

2-Benzyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-14-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10 13-azabicyclo[10.2.1]pentadeca-12(15),14-diene;

2-Methyl-15-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 14-azabicyclo[11.2.1]pentadeca-13(16),15-diene; 15 2-(2-Ηydroxy-«-butyl)-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-(2-Chloro-n-butyl)-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- 20 azabicyclo[7.2. l]dodeca-9(12),l 1-diene; l l-((3-Ethoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-l l-((3-ethoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 25 2-«-Propyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Pentyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Benzyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- 30 azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Ethyl- 11 -((3-ethoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-ll(14),13-diene; 35 13-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Ethyl-12-methyl-13-((3-benzyloxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- 2-ylidene)methyl)- 12-azabicyclo[9.2.1 ]tetradeca- 11(14), 13-diene; 5 2-Ethyl-12-methyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 12-azabicyclo [9.2.1 ]tetradeca- 11 ( 14), 13 -diene;

2-n-Propyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-12-azabicyclo[9.2. l]tetradeca-l 1(14), 13-diene; and

2-«-Butyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10 12-azabicyclo[9.2.1]tetradeca-l 1 (14), 13-diene or a pharmaceutically acceptable salt thereof. For use in the present methods for treating or preventing a viral infection, a prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -Η, -CΗ₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; 15 R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl,

-CH₂C₆H₅, -SiR₁₀R_πR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₃ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH(R₁₄)(R₁₅) wherein R,₄ and R₁₅ are independently C,-C,₂ straight chain alkyl, -C(O)C,- 20 C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(Cl)C_rC₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyI)methyI, -(4-pyridyl)methyl, and -CH₂C₆H₅, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups;

R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl 25 and -C₆H₅;

R_π and R₁₂ are independently C_rC₃ straight or branched chain alkyl; and R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5.

For use in the present methods for treating or preventing a viral infection, a second 30 prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, 35 (l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R₁₆ and R,₇ are -H; and m is an integer ranging from 1 to 5.

For use in the present methods for treating or preventing a viral infection, a third prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is -H;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, and -CH₂C₆H₅; R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5.

For use in the present methods for treating or preventing a viral infection, a fourth prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that when m is 3, R₃ is not -CH₂CH₃ and when m is 1, R₃ is not -(CH₂)₃CH₃.

For use in the methods for treating or preventing a viral infection, a fifth prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, (l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R,₆ and R_I7 are -H; and m is an integer ranging from 1 to 5.

For use in the methods for treating or preventing a viral infection,_. a sixth prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I).: each R, is independently selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl;

R,₆ and R₁₇ are -H; and m is 2, 4, or 5. For use in the present methods for treating or preventing a viral infection, a seventh prefened subclass of the compounds of Formula (T) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, -(CH₂)₂CH₃, and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydxoxy)butyl, and (l-chloro)butyl; m is an integer ranging from 1 to 5; when m is 3 and R₂ is -CH₃, then R₁₆ is selected from the group consisting of -H and -CH₃ and R₁₇ is selected from the group consisting of -H and -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R₁₆ and R,₇ are -H only.

The invention further provides methods for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (I) or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl,

-CH₂C₆H₅, -SiR,₀R„R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₃ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH(R₁₄)(R,₅) wherein R₁₄ and R,₅ are independently C,-C,₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups;

R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅; R,, and R,₂ are independently C,-C₃ straight or branched chain alkyl; m is an integer ranging from 1 to 5; and when m is 3 and R₂ is -CH₂CH₃, then R₁₆ is -H or -CH₃ and R,₇ is -H; when m is 3 and R₂ is -CH₃, then R_I6 is -H or -CH₃ and R_I7 is -H or -COOEt; and 5 when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R,₆ and R₁₇ are

-H only.

A prefened compound for use in the methods for inhibiting the replication or infectivity of a virus is butyl-meta-cycloheptylprodiginine or a pharmaceutically acceptable salt thereof. 10 A prefened compound for use in the methods for inhibiting the replication or infectivity of a virus is metacycloprodigiosin or a pharmaceutically acceptable salt thereof.

2-Ethyl- 11 -((3-methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- 15 azabicyclo[7.2.1]dodeca-9(12),l 1-diene; ll-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 20 2-«-Propyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-π-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Benzyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 25 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-«-Pentyl-ll-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-n-Pentyl-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9( 12), 11 -diene; 30 (S)-2-n-Butyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9( 12), 11 -diene;

(R)-2-«-Butyl- 11 -((3-methoxy-5-( lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9( 12), 11 -diene;

(S)-2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 35 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; (R)-2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

(S)-2-Methyl- 11 -((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(l 2), 11 -diene; (R)-2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-n-Propyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pyrrol-2- ylidene)methyl)-l 0-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

(R)-2-«-Proρyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-12-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-Ethyl- 12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 11 - azabicyclo[8.2.1]trideca-10(13),12-diene; 2-n-Proρyl-12-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-fl-Butyl- 12-((3-methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-n-Pentyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 1 l-azabicyclo[8.2.1]trideca-10(13),12-diene;

12-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-l l- azabicyclo[8.2.1]trideca-10(13),12-diene;

2-Methyl-13-((3-methoxy-5-(lH-ρynol-2-yl)-2H-ρynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene; 13-((3-Methoxy-5-(iH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Ethyl-12-methyl-13-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- 2-ylidene)methyl)- 12-azabicyclo [9.2.1 Jtetradeca- 11 ( 14), 13 -diene;

2-Ethyl- 12-methyl- 13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 12-azabicyclo[9.2.1 Jtetradeca- 11(14), 13-diene;

2-«-Butyl- 13 -((3 -methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene; 14-((3 -Methoxy-5-( lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- 13- azabicyclo[10.2.1]pentadeca-12(15),14-diene;

2-Butyl-l 1 -((3-methoxy-5-(l -methyl- lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(l 2), 11-diene; 2-Butyl- 11 -((3-methoxy-5-(l -methyl- lH-pynoI-2-yl)-2H-pynol-2- ylidene)methyl)- 10-methyl- 10-azabicyclo[7.2. l]dodeca-9(l 2), 11 -diene;

2-Butyl- 11 -((3-methoxy-5-( lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- methyl-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Ethyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl-ll-((3-hydroxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 15 ll-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-l l-((3-benzyloxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-7z-Propyl- 11 -((3 -benzyloxy-5-( lH-pynol-2-yl)-2H-pynol-2- 20 ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-n-Pentyl- 11 -((3-benzyloxy-5-(lH-pynoI-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2. l]dodeca-9(12), 11-diene;

2-Benzyl- 11 -((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 25 2-Methyl-14-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

13-azabicyclo[10.2.1]pentadeca-12(15),14-diene;

15-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-14- azabicyclo[l 1.2.1 jpentadeca- 13(16), 15-diene;

2-Methyl-15-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 30 14-azabicyclo[11.2.1]pentadeca-13(16),15-diene;

2-(2-Ηydroxy-«-butyl)-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; *

2-(2-Chloro-«-butyl)-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2. l]dodeca-9(12), 11 -diene; 35 2-Butyl- 11 -((3-ethoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; ll-((3-Ethoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 2-Methyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-n-Propyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Pentyl-ll-((3-ethoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyI)- 10 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Benzyl- 11 -((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Ethyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 15 2-Methyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2.1 ]tetradeca- 11(14), 13-diene;

13-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2.1]tetradeca-ll(14),13-diene;

2-Ethyl-12-methyl-13-((3-benzyloxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- 20 2-ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Ethyl- 12-methyl- 13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 12-azabicyclo[9.2.1 ]tetradeca- 11 (14), 13-diene;

2-n-Proρyl- 13-((3-benzyloxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-ll(14),13-diene; and 25 2-n-Butyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-yIidene)methyl)-

12-azabicyclo[9.2.1]tetradeca-l 1 (14), 13-diene or a pharmaceutically acceptable salt thereof.

For use in the methods for inhibiting the replication or infectivity of a virus, a prefened subclass of the compounds of Formula (I) are those wherein: each R, is independently selected from the group consisting of -Η, -CΗ₃, -CH₂CH₃, 30 -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H„C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR_I0R..R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₃ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, 35 -CH(R₁₄)(R₁₅) wherein R,₄ and R,₅ are independently C,-C₁₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups; R_I0 is selected from the group consisting of C,-C₄ straight or branched chain alkyl, and -C₆H₅;

R_π and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and

R,₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5. For use in the methods for inhibiting the replication or infectivity of a virus, a second prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃;

(l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl;

R,₆ and R,₇ are -H; and m is an integer ranging from 1 to 5.

For use in the methods for inhibiting the replication or infectivity of a virus, a third prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is -H;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, and -CH₂C₆H₅;

R,₆ and R,₇ are -H; and m is an integer ranging from 1 to 5.

For use in the methods for inhibiting the replication or infectivity of a virus, a fourth prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group, consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that when m is 3, R₃ is not -CH₂CH₃ and when m is 1, R₃ is not -(CH₂)₃CH₃.

For use in the methods for inhibiting the replication or infectivity of a virus, a fifth prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅;

R₁₆ and R,₇ are -H; and m is an integer ranging from 1 to 5.

For use in the methods for inhibiting the replication or infectivity of a virus, a sixth prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R₁₆ and R₁₇ are -H; and m is 2, 4, or 5.

For use in the methods for inhibiting the replication or infectivity of a virus, a seventh prefened subclass of the compounds of Formula (I) is that wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H and -CH₃;

R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydxoxy)butyl, and (l-chloro)butyl; m is an integer ranging from 1 to 5; when m is 3 and R₂ is -CH₃, then R,₆ is selected from the group consisting of -H and -CH₃ and R₁₇is selected from the group consisting of -H and -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R_I6 and R_I7 are -H only. 4.2. FORMULA II

The present invention still further provides novel compounds having the general Formula (H):

. II

and pharmaceutically acceptable salts thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; R₂ is selected from the group consisting of -H, C C_l2 straight chain alkyl,

R₄ is selected from the group consisting of -H and C,-C,₂ straight chain alkyl; R₅ is selected from the group consisting of -H, C,-C₄ straight chain alkyl and -C₆H₅; R₁₀ is selected from the group consisting of -C,-C₄, straight or branched chain alkyl and -C₆H₅;

R_u and R₁₂ are independently C,-C₃ straight or branched chained alkyl; and n is an integer ranging from 1 to 6; with the proviso that the compound of Formula (H) is not: cycloprodigiosin, or

4-ethyl-2,4,5,6-tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl-)-2H-ρynol-2- ylidene)methyl)- 1 -methyl-cyclopenta(c)pynole.

The compounds of Formula (H) and pharmaceutically acceptable salts thereof are useful for treating or preventing cancer or neoplastic disease in a patient in need of such treatment or prevention. The compounds of Formula (H) and pharmaceutically acceptable salts thereof are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The compounds of Formula (II) and pharmaceutically acceptable salts thereof are useful for treating or preventing a viral infection in a patient in need of such treatment or prevention. The compounds of Formula (H) and pharmaceutically acceptable salts thereof are also useful for inhibiting the replication or infectivity of a virus. A prefened subclass of the compounds of Formula (Ft) is that wherein: R, is selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ and R₅ are independently selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and n is an integer ranging from 1 to 3. with the proviso that the compound of Formula (H) is not: cycloprodigiosin or

4-ethyl-2,4,5,6-tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl-)-2H-pynol-2- ylidene)methyl)- 1 -methyl-cyclopenta(c)pynole.

A prefened second subclass of the compounds of Formula (H) is that wherein: R, is selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ is selected from the group consisting of -H and C,-C₁₂ straight chain alkyl; R₅ is -H; and n is an integer ranging from 1 to 3.

A third prefened subclass of the compounds of Formula (H) is that wherein: R, is selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ is -H;

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -n-C₄H₉, and -C₆H₅; and n is an integer ranging from 1 to 3.

In a prefened embodiment, the compounds of Formula (H) are selected from the group consisting of:

4,5,6,7-Tetrahydro-3-((3-benzyloxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- 2-ylidene)methyl)- 1 ,4-dimethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-4-ethyl-2H-isoindole; 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-4-ethyl- 1 -methyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 1 ,4-diethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l-ethyl-4-methyl-2H-isoindole; and 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l-ethyl-2H-isoindole or a pharmaceutically acceptable salt thereof.

The present invention further provides compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula (Η) or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (Η): each R. is independently selected from the group consisting of -Η, -CΗ₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R, is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR,₀R_πR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₄ is selected from the group consisting of -H and C,-C,₂ straight chain alkyl; R₅ is selected from the group consisting of -H, C,-C₄ straight chain alkyl and -C₆H₅; R_I0 is selected from the group consisting of C,-C₄ straight or branched chain alkyl, and -C₆H₅; R-_j and R₁₂ are independently selected from the group consisting of -CH₃, -CH₂CH₃, and -C₃H₇; and n is an integer ranging from 1 to 6; with the proviso that the compound of Formula (H) is not: cycloprodigiosin, or 4-ethyl-2,4,5,6-tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl-)-2H-pynol-2- ylidene)methyl)- 1 -methyl-cyclopenta(c)pynole.

The compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (H) or a pharmaceutically acceptable salt thereof are useful for treating or preventing cancer or neoplastic disease in a patient in need of such treatment or prevention. These compositions are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (H) or a pharmaceutically acceptable salt thereof are useful for treating or preventing a viral infection in a patient in need of such treatment or prevention. These compositions are also useful for inhibiting the replication and/or infectivity of a virus. A prefened subclass of the compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (H) or a pharmaceutically acceptable salt thereof is that wherein, in the compound of Formula (II):

R, is selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ and R₅ are independently selected from the group consisting of -H, -CH₃, and -CH₂CH₃; n is an integer ranging from 1 to 3. with the proviso that the compound of Formula (H) is not: cycloprodigiosin or

4-ethyl-2,4,5,6-tetrahydro-3-((3-methoxy-5-(lH-ρynol-2-yl-)-2H-pynol-2- ylidene)methyl)- 1 -methyl-cyclopenta(c)pynole.

A second prefened subclass of the compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (H) or a pharmaceutically acceptable salt thereof is that wherein, in the compound of Formula (H) :

R, is selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅, R₄ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and a C₃-C,₂ straight chain alkyl; R_s is -H; and n is an integer ranging from 1 to 3.

A third prefened subclass of the compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (H) or a pharmaceutically acceptable salt thereof is that wherein, in the compound of Formula (H): R_j is selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ is -H;

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -H-C₄H₉, and -C₆H₅; and n is an integer ranging from 1 to 3.

In prefened embodiments, the compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (H) or a pharmaceutically acceptable salt thereof is that, in the compound of Formula (H) is selected from the group consisting of:

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-4-ethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-ρynol-2-yI)-2H-pynol-2- ylidene)methyl)-4-ethyl- 1 -methyl-2H-isoindole; 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 1 ,4-diethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 1 -ethyl-4-methyl-2H-isoindole; and 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l-ethyl-2H-isoindole or a pharmaceutically acceptable salt thereof.

The invention provides methods for treating or preventing cancer or a neoplastic disease comprising administering to a patient in need of such treatment or prevention a composition comprising a therapeutically effective amount of a compound of Formula (Η) or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -Η, -CΗ₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR,₀R_πR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₄ is selected from the group consisting of -H and C_rC,₂ straight chain alkyl; R₅ is selected from the group consisting of -H, C,-C₄ straight chain alkyl and -C₆H₅; R,₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl, and -C₆H₅; R, , and R₁₂ are independently selected from the group consisting of C,-C₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6; with the proviso that the compound of Formula (H) is not: cycloprodigiosin. A prefened compound for use in treating or preventing cancer or a neoplastic disease is:

4-ethyl-2,4,5,6-tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl-)-2H-pynol-2- ylidene)methyl)-l-methyl-cyclopenta(c)pynole or a pharmaceutically acceptable salt thereof. Other prefened compounds for the method are selected from the group consisting of:

4,5,6,7-Tetrahydro-3-((3-benzyloxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 1 ,4-dimethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 1 ,4-diethyl-2H-isoindole; 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 1 -ethyl-4-methyl-2H-isoindole; and

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l-ethyl-2H-isoindoIe or a pharmaceutically acceptable salt thereof.

For use in treating or preventing cancer or a neoplastic disease, a prefened subclass of the compounds of Formula (Η) are those wherein, in the compound of Formula (Η): R, is selected from the group consisting of -Η and -CΗ₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ and R₅ are independently selected from the group consisting of -H, -CH₃, and -CH₂CH₃; n is an integer ranging from 1 to 3. with the proviso that the compound of Formula (H) is not: cycloprodigiosin.

For use in treating or preventing cancer or a neoplastic disease, a second prefened subclass of the compounds of Formula (H) is that wherein, in the compound of Formula (H): R. is selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and a C₃-C_I2 straight chain alkyl;

R₅ is -H; and n is an integer ranging from 1 to 3.

For use in treating or preventing cancer or a neoplastic disease, a third prefened subclass of the compounds of Formula (H) is that wherein, in the compound of Formula (H): R, is selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ is -H;

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -ra-C₄H₉, and -C₆H₅; and n is an integer ranging from 1 to 3.

For use in treating or preventing cancer or a neoplastic disease, a fourth prefened subclass of the compounds of Formula (H) is that wherein, in the compound of Formula (H): R, is selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and a C₃-C,₂ straight chain alkyl; R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -«-C₄H₉, and

-C₆H₅; and n is an integer ranging from 1 to 3; with the proviso that the compound of Formula (II) is not: cycloprodigiosin. The invention provides methods for inhibiting the growth of a cancer cell or neoplastic cell comprising a contacting a cancer cell or neoplastic cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (II) or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_uR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₄ is selected from the group consisting of -H and C,-C,₂ straight chain alkyl; R₅ is selected from the group consisting of -H, C,-C₄ straight chain alkyl and -C₆H₅;

R, , and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and n is a integer from 1 to 6; with the proviso that the compound of Formula (H) is not: cycloprodigiosin.

A prefened compound for use in the methods for inhibiting the growth of a cancer or neoplastic cell is:

4-ethyl-2,4,5,6-tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl-)-2H-pynol-2- ylidene)methyl)-l -methyl-cyclopenta(c)pynole or a pharmaceutically acceptable salt thereof.

Other prefened compounds for the method are selected from the group consisting of:

4,5 ,6,7-Tetrahydro-3-((3-benzyloxy-5-(l -methyl- lH-pynol-2-yl)-2H-pynol- 2-ylidene)methyl)- 1 ,4-dimethyl-2H-isoindole; 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-4-ethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-4-ethyl- 1 -methyl-2H-isoindole; 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 1 ,4-diethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l-ethyl-4-methyl-2H-isoindole; and

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 1 -ethyl-2H-isoindole or a pharmaceutically acceptable salt thereof.

For use in the present methods for inhibiting the growth of a cancer or neoplastic cell, a prefened subclass of the compounds of Formula (II) is that wherein, in the compound of Formula (Η):

R, is selected from the group consisting of -Η and -CΗ₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

R₄ and R₅ are independently selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and n is an integer ranging from 1 to 3; with the proviso that the compound of Formula (H) is not: cycloprodigiosin.

For use in the present methods for inhibiting the growth of a cancer or neoplastic cell, a second prefened subclass of the compounds of Formula (H) is that wherein, in the compound of Formula (H):

R, is selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

R₄ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and a C₃-C,₂ straight chain alkyl;

R₅ is -H; and n is an integer ranging from 1 to 3. For use in the present methods for inhibiting the growth of a cancer or neoplastic cell, a third prefened subclass of the compounds of Formula (H) is that wherein, in the compound of Formula (H):

R, is selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ is -H; R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -«-C₄H₉, and -C₆H₅; n is a integer from 1 to 3.

For use in the present methods for inhibiting the growth of a cancer or neoplastic cell, a fourth prefened subclass of the compounds of Formula (H) is that wherein, in the compound of Formula (H):

R, is selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH,C₆H₅;

R₄ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and a C₃-C₁₂ straight chain alkyl;

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -n-C₄H₉, and -C₆H₅; and n is an integer ranging from 1 to 3; with the proviso that the compound of Formula (H) is not: cycloprodigiosin.

The invention provides methods for treating or preventing a viral infection comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (II) or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR,₀R„R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₄ is selected from the group consisting of -H and C,-C₁₂ straight chain alkyl;

R₅ is selected from the group consisting of -H, C,-C₄ straight chain alkyl and -C₆H₅;

R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl, and -C₆H₅; R, , and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and n is a integer from 1 to 6. Prefened compounds for use in the method for treating or preventing a viral infection are: cycloprodigiosin and 4-ethyl-2,4,5,6-tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl-)-2H-pynol-2- ylidene)methyl)-l-methyl-cyclopenta(c)pynole, or pharmaceutically acceptable salts thereof.

4,5 ,6,7-Tetrahydro-3 -((3 -methoxy-5-( lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 1 ,4-diethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l-ethyl-2H-isoindole or a pharmaceutically acceptable salt thereof.

For use in the present methods for treating or preventing a viral infection, a prefened subclass of the compounds of Formula (II) is that wherein, in the compound of Formula (II): R, is selected from the group consisting of -Η and -CΗ₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ and R₅ are independently selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and n is an integer ranging from 1 to 3. For use in the present methods for treating or preventing a viral infection, a second prefened subclass of the compounds of Formula (H) is that wherein, in the compound of Formula (H):

R, is selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and a C₃-C,₂ straight chain alkyl;

R₅ is -H; and n is an integer ranging from 1 to 3. For use in the present methods for treating or preventing a viral infection, a third prefened subclass of the compounds of Formula (H) is that wherein, in the compound of Formula (If):

R, is selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H_S;

R₄ is -H;

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -«-C₄H₉, and -C₆H₅; and n is an integer ranging from 1 to 3. For use in the present methods for treating or preventing a viral infection, a fourth prefened subclass of the compounds of Formula (H) is that wherein, in the compound of Formula (π):

R, is selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and a C₃-C,₂ straight chain alkyl;

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -«-C₄H₉, and -C₆H₅; and n is an integer ranging from 1 to 3. The invention provides methods for inhibiting the replication or infectivity of a virus comprising contacting a virus or a virus-infected cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (H) or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H_s, and -C(O)CH₃;

R*₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl, and -C₆H₅;

R, , and R₁₂ are independently C_rC₃ straight or branched chain alkyl; and n is a integer from 1 to 6. Prefened compounds for use in the methods for treating or preventing a viral infection are: cycloprodigiosin and

4-ethyl-2,4,5,6-tetrahydro-3-((3-methoxy-5-(lH-ρynol-2-yl-)-2H-pynol-2- ylidene)methyl)-l-methyl-cyclopenta(c)pynole, or pharmaceutically acceptable salts thereof. Other prefened compounds for the method are selected from the group consisting of:

4,5,6,7-Tetrahydro-3-((3-benzyloxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol-2- ylidene)m ethyl)- l,4-dimethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)-4-ethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)-4-ethyl- 1 -methyl-2H-isoindole;

For use in the present methods for treating or preventing a viral infection, a prefened subclass of the compounds of Formula (Η) is that wherein, in the compound of Formula (II): R, is selected from the group consisting of -Η and -CΗ₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₃; R₄ and R_s are independently selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and n is an integer ranging from 1 to 3.

For use in the present methods for treating or preventing a viral infection, a second prefened subclass of the compounds of Formula (H) is that wherein, in the compound of Formula (H):

R, is selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅,

R_s is -H; and n is an integer ranging from 1 to 3. For use in the present methods for treating or preventing a viral infection, a third prefened subclass of the compounds of Formula (H) is that wherein, in the compound of Formula (TI):

R₄ is -H;

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -«-C₄H₉, and -C₆H₅; and n is an integer ranging from 1 to 3. For use in the present methods for treating or preventing a viral infection, a fourth prefened subclass of the compounds of Formula (H) is that wherein, in the compound of Formula (H):

R, is selected from the group consisting of -H and -CH₃;

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -«-C₄H₉, and C₆H₅; and n is an integer ranging from 1 to 3.

4.3. FORMULA HI

III

and pharmaceutically acceptable salts thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_πR.₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R,, and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6; with the proviso that the compound of Formula (HI) is not: orthobutylcycloheptylprodiginine,

4-methoxy-5-((4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH-pynole),

4-methoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2, 2'-bi-lH- pynole),

4-ethoxy-5-(4-hexyl-(4,5 ,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2, 2'-bi- 1H- pyrrole), or

4-propoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2, 2'-bi-lH- pynole).

The compounds of Formula (III) and pharmaceutically acceptable salts thereof are useful for treating or preventing cancer or neoplastic disease in a patient in need of such treatment or prevention. The compounds of Formula (HI) and pharmaceutically acceptable salts thereof are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The compounds of Formula (IH) and pharmaceutically acceptable salts thereof are useful for treating or preventing a viral infection in a patient in need of such treatment or prevention. The compounds of Formula (in) and pharmaceutically acceptable salts thereof are also useful for inhibiting the replication or infectivity of a virus.

A prefened subclass of the compounds of Formula (HI) is that wherein: each R, is independently selected from the group consisting of -H and -CH₃;

R₅ is selected from the group consisting of -CH₃ and -CH₂CH₃; and n is an integer ranging from 1 to 3.

In a prefened embodiment, the compounds of Formula (HI) are selected from the group consisting of 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-5-methyl- lH-indole, and 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol- 2-yl)-2H-pynol-2-ylidene)methyl)-lH-indole or a pharmaceutically acceptable salt thereof. The present invention further provides compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula (HI) or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_nR_I2, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₅ is selected from the group consisting of -H, C,-C₆ straight chain alkyl and -C₆H₅; Rio ^1S selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R,, and R,₂ are independently C,-C₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6; with the proviso that the compound of Formula (HI) is not: orthobutylcycloheptylprodiginine;

4-methoxy-5-((4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH-pynole),

4-methoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH- pynole),

4-ethoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH- pynole), or

4-ρroρoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2, 2'-bi-lH- pynole).

The compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (HI) or a pharmaceutically acceptable salt thereof are useful for treating or preventing cancer or neoplastic disease in a patient in need of such treatment or prevention. These compositions are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (HI) or a pharmaceutically acceptable salt thereof are useful for treating or preventing a viral infection in a patient in need of such treatment or prevention. These compositions are also useful for inhibiting the replication or infectivity of a virus.

A prefened subclass of the compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (HI) or a pharmaceutically acceptable salt thereof are those wherein, in the compound of Formula (IH): each R, is independently selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R_s is selected from the group consisting of -CH₃ and -CH₂CH₃; and n is an integer ranging from 1 to 3.

In prefened embodiments, the compositions comprise a pharmaceutically acceptable carrier and a compound of Formula (HI) selected from the group consisting of selected from the group consisting of 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-5-methyl- lH-indole, and 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol- 2-yl)-2H-pynol-2-ylidene)methyl)-lH-indole, or a pharmaceutically acceptable salt thereof.

The invention further provides methods for treating or preventing cancer or a neoplastic disease comprising administering to a patient in need of such treatment or prevention a composition comprising a therapeutically effective amount of a compound of Formula (HI) or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR,oR„R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅; R_j , and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6. Prefened compounds for use in the methods for treating or preventing cancer or a neoplastic disease are:

4-methoxy-5-((4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH-pynole), 4-methoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH- pynole),

4-ethoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH- pynole), and

4-proρoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH- pynole), or pharmaceutically acceptable salts thereof.

Other prefened compounds for the method are selected from the group consisting of 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-5- methyl-lH-indole and 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-lH-indole, or a pharmaceutically acceptable salt thereof. For use in the present methods for treating or preventing cancer or a neoplastic disease, a prefened subclass of the compounds of Formula (IH) is that wherein, in the compound of Formula (HI) : each R, is independently selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

Q R₅ is selected from the group consisting of -CH₃, and -CH₂CH₃; and n is an integer ranging from 1 to 3.

For use in the present methods for treating or preventing cancer or a neoplastic disease, a second prefened subclass of the compounds of Formula (IH) is that wherein, in the compound of Formula (HI): each R, is independently selected from the group consisting of -H and -CH₃;

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -«-C₄H₉, -(CH₂)₅CH₃₎ and -C₆H₅; and n is an integer ranging from 1 to 3.

The invention further provides methods for inhibiting the growth of a cancer cell or neoplastic cell comprising a contacting a cancer cell or neoplastic cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (IH) or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃,

-CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R.,R_I2, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; R₅ is selected from the group consisting of -H, C,-C₆ straight chain alkyl and -C₆H₅;

R,, and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6. Prefened compounds for use in the methods for inhibiting the growth of a cancer or neoplastic cell are:

4-methoxy-5-((4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH-pynole),

4-methoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2*-bi-lH- pynole), 4-ethoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH- pynole), and

4-propoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH- pynole), or a pharmaceutically acceptable salt thereof. Other prefened compounds for use in the method are selected from the group consisting of 4,5,6,7-Tetr ahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-5-methyl-lH-indole and 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2- yl)-2H-ρynol-2-ylidene)methyl)-lH-indole, or a pharmaceutically acceptable salt thereof. For use in the present methods for inhibiting the growth of a cancer or neoplastic cell, a prefened subclass of the compounds of Formula (HI) are those wherein, in the compound of Formula (HI): each R, is independently selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₅ is selected from the group consisting of -CH₃ and -CH₂CH₃; and n is an integer ranging from 1 to 3.

For use in the present methods for inhibiting the growth of a cancer or neoplastic cell, a second prefened subclass of the compounds of Formula (HI) is that wherein, in the compound of Formula (HI): each R, is independently selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -n-C₄H₉, -(CH₂)₅CH_3ι and -C₆H₅; and n is an integer ranging from 1 to 3.

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_uR,₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₅ is selected from the group consisting of -H, C,-C₆ straight chain alkyl and -C₆H₅; R,₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R,, and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6. Prefened compounds for use in the methods for treating or preventing a viral infection are:

4-methoxy-5-((4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH-pynole),

4-ethoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH- pyrrole), and

4-proρoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH- pynole), or a pharmaceutically acceptable salt thereof.

Other prefened compounds for use in the method are selected from the group consisting of 4,5,6, 7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-5-methyl-lH-indole and 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2- yl)-2H-pynol-2-ylidene)methyl)-lH-indole, or a pharmaceutically acceptable salt thereof.

For use in the present methods for treating or preventing a viral infection, a prefened subclass of the compounds of Formula (HI) is that wherein, in the compound of Formula (HI): each R, is independently selected from the group consisting of -H and -CH₃;

R₅ is selected from the group consisting of -CH₃ and -CH₂CH₃; and n an integer ranging from 1 to 3.

For use in the present methods for treating or preventing a viral infection, a second prefened subclass of the compounds of Formula (HI) is that wherein, in the compound of Formula (UX): each R, is independently selected from the group consisting of -H, and -CH₃;

R₅is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -«-C₄H₉, -(CH₂)₅CH₃, and -C₆H₅; and n is an integer ranging from 1 to 3.

The invention further provides methods for inhibiting the replication or infectivity of a virus comprising contacting a virus or a virus-infected cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (IH) or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR_I0R„R_I2, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₁₀ is selected from the group consisting of C,-C₆ straight or branched chain alkyl and -C₆H₅;

R,, and R,₂ are independently C,-C₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6.

Prefened compounds for use in the method for inhibiting the replication or infectivity of a virus are:

4-methoxy-5-((4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH-pynole),

4-propoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH- pynole), or a pharmaceutically acceptable salt thereof. Other prefened compounds for use in the method are selected from the group consisting of 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-5-methyl-lH-indole and 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2- yl)-2H-pynol-2-ylidene)methyl)-lH-indole, or a pharmaceutically acceptable salt thereof.

For use in the present methods for inhibiting the replication or infectivity of a virus, a prefened subclass of the compounds of Formula (IΗ) is that wherein, in the compound of Formula (HI): each R, is independently selected from the group consisting of -H and -CH₃;

R₅is selected from the group consisting of -CH₃ and -CH₂CH₃; and n is an integer ranging from 1 to 3.

For use in the present methods for inhibiting the replication or infectivity of a virus, a second prefened subclass of the compounds of Formula (πi) is that wherein, in the compound of Formula (IH): each R, is independently selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₅is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -n-C₄H₉, -(CH₂)₅CH_3> and -C₆H₅; and n is an integer ranging from 1 to 3.

4.4. FORMULA IV

and pharmaceutically acceptable salts thereof, wherein:

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR.₀R_πR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R,, and R,₂ are independently C,-C₃ straight or branched chain alkyl; and p is as integer from 6 to 8; with the proviso that the compound of Formula (IN) is not: cyclononylprodiginine, methylcyclooctylprodiginine, methylcyclodecylprodiginine, ethylcyclononylprodiginine,

R39FF, R39MF, R39SF, 61 OFF, or 610MF. The compounds of Formula (IN) and pharmaceutically acceptable salts thereof are useful for treating or preventing cancer or neoplastic disease in a patient in need of such treatment or prevention. The compounds of Formula (IN) and pharmaceutically acceptable salts thereof are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The compounds of Formula (TV) and pharmaceutically acceptable salts thereof are useful for treating or preventing a viral infection in a patient in need of such treatment or prevention. The compounds of Formula (IV) and pharmaceutically acceptable salts thereof are also useful for inhibiting the replication or infectivity of a virus.

A prefened subclass of the compounds of Formula (IV) is that wherein: R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and p is an integer ranging from 6 to 8; with the proviso that the compound of Formula (IV) is not: cyclononylprodiginine, methylcyclooctylprodiginine, methylcyclodecylprodiginine, ethylcyclononylprodiginine,

R39FF,

R39MF, R39SF,

61 OFF, or

610MF.

A second prefened subclass of the compounds of Formula (IV) is that wherein:

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H_S; R₆ is -H; and p is an integer of 6 or 8.

A third prefened subclass of the compounds of Formula (IV) is that wherein:

R₂ is selected from the group consisting of -CH₂CH₃, and -CH₂C₆H₅;

R^ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and p is an integer ranging from 6 to 8.

In one embodiment, prefened compounds of Formula (IN) are selected from the group consisting of 4-Methoxy-23,24,25-triazatetracyclo(18.2.1.1²'⁵.l⁷'¹⁰)pentacosa- 2(25),3,5,7,9,20,22-heptaene, and 4-Methoxy-24,25,26- triazatetracyclo(19.2.1.1²'⁵.l⁷-¹⁰)hexacosa-2(26),3,5,7,9,21,23-heptaene or a pharmaceutically acceptable salt thereof. The present invention further provides compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula (IV) or a pharmaceutically acceptable salt thereof, wherein:

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R, ,R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃;

R_I0 is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅; R, _j and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and p is an integer ranging from 6 to 8; with the proviso that the compound of Formula (IV) is not: cyclononylprodiginine, methylcyclooctylprodiginine, methylcyclodecylprodiginine, ethylcyclononylprodiginine,

R39FF,

R39MF,

R39SF, 61 OFF, or

610MF.

The compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (TV) or a pharmaceutically acceptable salt thereof are useful for treating or preventing cancer or neoplastic disease in a patient in need of such treatment or prevention. These compositions are also useful for inhibiting the growth of a cancer cell or neoplastic cell. The compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (IV) or a pharmaceutically acceptable salt thereof are useful for treating or preventing a viral infection in a patient in need of such treatment or prevention. These compositions are also useful for inhibiting the replication or infectivity of a virus. A prefened subclass of the compositions comprising a pharmaceutically acceptable carrier and compound of Formula (TV) or a pharmaceutically acceptable salt thereof is that wherein, in the compound of Formula (IV):

R39FF, R39MF, R39SF, 61 OFF, or 610MF.

A second prefened subclass of the compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (IV) or a pharmaceutically acceptable salt thereof is that wherein, in the compound of Formula (IV):

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₆ is -H; p is 6 or 8.

A third prefened subclass of the compositions comprising a pharmaceutically acceptable carrier and a compound of Formula (IN) or a pharmaceutically acceptable salt thereof is that wherein, in the compound of Formula (IV): R₂ is selected from the group consisting of -CH₂CH₃, and -CH₂C₆H₅;

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; p is an integer ranging from 6 to 8. In prefened embodiments, the compositions comprise a pharmaceutically acceptable carrier and a compound of Formula (IN) selected from the group consisting of 4-Methoxy- 23,24,25-triazatetracyclo(18.2.1.1^2,5.l⁷-¹⁰)pentacosa-2(25),3,5,7,9,20,22-heptaene and 4- Methoxy-24,25,26-triazatetracyclo(l 9.2.1.1^2,5. l⁷-¹⁰)hexacosa-2(26),3,5,7,9,21 ,23-heptaene, or a pharmaceutically acceptable salt thereof.

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_nR_I2, -C(O)CH₃, -C(O)C₆H_s, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R_u and R_I2 are independently C,-C₃ straight or branched chain alkyl; and p is an integer ranging from 6 to 8. Prefened compounds for use in the method for treating or preventing cancer are: cyclononylprodiginine, methylcyclooctylprodiginine, methylcyclodecylprodiginine, ethylcyclononylprodiginine, R39FF,

R39MF, R39SF, 61 OFF, and

61 OMF, or a pharmaceutically acceptable salt thereof. Other prefened compounds for use in the method are selected from the group consisting of 4-Methoxy-23,24,25-triazatetracyclo(l 8.2.1. I^2,5. l^7,10)pentacosa- 2(25),3,5,7,9,20,22-heptaene and 4-Methoxy-24,25,26- triazatetracyclo(19.2.1.1²'⁵.l^7,10)hexacosa-2(26),3,5,7,9,21,23-heptaene, or a pharmaceutically acceptable salt thereof. For use in the present methods for treating or preventing cancer, a prefened subclass of the compounds of Formula (IV) is that wherein, in the compound of Formula (IV): R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and p is an integer ranging from 6 to 8. For use in the present methods for treating or preventing cancer, a second prefened subclass of the compounds of Formula (IV) is that wherein, in the compound of Formula (IV):

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₆ is -H; and p is 6 or 8.

For use in the present methods for treating or preventing cancer, a third prefened subclass of the compounds of Formula (IV) is that wherein, in the compound of Formula (IV):

R₂ is selected from the group consisting of -CH₂CH₃, and -CH₂C₆H₅; R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and p is an integer ranging from 6 to 8.

For use in the present methods for treating or preventing cancer, a fourth prefened subclass of the compounds of Formula (IV) is that wherein, in the compound of Formula (IV): R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and p is an integer ranging from 6 to 8.

The invention further provides methods for inhibiting the growth of a cancer cell or neoplastic cell comprising a contacting a cancer cell or neoplastic cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (IV) or a pharmaceutically acceptable salt thereof, wherein:

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR,₀R„R,₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃;

R_n and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and p is an integer ranging from 6 to 8. Prefened compounds for use in the method for inhibiting the growth of a cancer or neoplastic cell are: cyclononylprodiginine, methylcyclooctylprodiginine, methylcyclodecylprodiginine, ethylcyclononylprodiginine,

R39FF,

R39MF,

R39SF,

61 OFF, and 61 OMF, or a pharmaceutically acceptable salt thereof.

Other prefened compounds for use in the method are selected from the group consisting of 4-Methoxy-23,24,25-triazatetracyclo(l 8.2.1.1²'⁵. l⁷-¹⁰)pentacosa- 2(25),3,5,7,9,20,22-heptaene and 4-Methoxy-24,25,26- triazatetracyclo(19.2.1.1²'⁵. ⁰)hexacosa-2(26),3,5,7,9,21,23-heptaene, or a pharmaceutically acceptable salt thereof. For use in the present methods for inhibiting the growth of a cancer or neoplastic cell, a prefened subclass of the compounds of Formula (IV) is that wherein, in the compound of Formula (IV):

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and p is an integer ranging from 6 to 8.

For use in the present methods for inhibiting the growth of a cancer or neoplastic cell, a second prefened subclass of the compounds of Formula (IV) is that wherein, in the compound of Formula (IV): R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; ^ is -H; p is an integer of 6 or 8.

For use in the present methods for inhibiting the growth of a cancer or neoplastic cell, a third prefened subclass of the compounds of Formula (IV) is that wherein, in the compound of Formula (IV) :

R₂ is selected from the group consisting of -CH₂CH₃, and -CH₂C₆H₅;

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; p is an integer ranging from 6 to 8.

For use in the present methods for inhibiting the growth of a cancer or neoplastic cell, a fourth prefened subclass of the compounds of Formula (IV) is that wherein, in the compound of Formula (IV):

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and p is an integer ranging from 6 to 8. The invention further provides methods for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (IV) or a pharmaceutically acceptable salt thereof, wherein: R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl,

-CH₂C₆H₅, -SiR.₀R_πR.₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃;

R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl, and -C₆H₅; R_n and R,₂ are independently C C₃ straight or branched chain alkyl; and p is an integer ranging from 6 to 8. Prefened compounds for use in the methods for treating or preventing a viral infection are: cyclononylprodiginine, methylcyclooctylprodiginine, methylcyclodecylprodiginine, ethylcyclononylprodiginine,

R39FF,

R39MF, R39SF,

61 OFF, and

610MF, or pharmaceutically acceptable salts thereof.

Other prefened compounds for use in the method are selected from the group consisting of 4-Methoxy-23,24,25-triazatetracyclo(l 8.2.1.1^2,5. l⁷'¹⁰)pentacosa- 2(25),3,5,7,9,20,22-heptaene and 4-Methoxy-24,25,26- triazatetracyclo(19.2.1.1^2,5.l^7,10)hexacosa-2(26),3,5,7,9,21,23-heptaene, or a pharmaceutically acceptable salt thereof.

For use in the present methods for treating or preventing a viral infection, a prefened subclass of the compounds of Formula (IV) is that wherein, in the compound of Formula (IV):

For use in the present methods for treating or preventing a viral infection, a second prefened subclass of the compounds of Formula (IN) is that wherein, in the compound of Formula (IV):

R₆ is -H; p is an integer of 6 or 8. For use in the present methods for treating or preventing a viral infection, a third prefened subclass of the compounds of Formula (IV) is that wherein, in the compound of Formula (IV):

R₂ is selected from the group consisting of -CH₂CH₃, and -CH₂C₆H₅;

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; p is an integer ranging from 6 to 8. For use in the present methods for treating or preventing a viral infection, a fourth prefened subclass of the compounds of Formula (IV) is that wherein, in the compound of Formula (IV):

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂ H₅; R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and p is an integer ranging from 6 to 8.

The invention further provides methods for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (IN) or a pharmaceutically acceptable salt thereof, wherein:

R₂ is selected from the group consisting of -H, C,-C_I2 straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_uR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R, , and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and p is an integer ranging from 6 to 8. Prefened compounds for use in the methods for inhibiting the replication or infectivity of a virus are: cyclononylprodiginine, methylcyclooctylprodiginine, methylcyclodecylprodiginine, ethylcyclononylprodiginine, R39FF,

R39MF,

R39SF,

61 OFF, and

610MF, or a pharmaceutically acceptable salt thereof. Other prefened compounds for use in the method are selected from the group consisting of 4-Methoxy-23,24,25-triazatetracyclo(18.2.1.1²'⁵. l⁷'¹⁰)pentacosa- 2(25),3,5,7,9,20,22-heptaene and 4-Methoxy-24,25,26- triazatetracyclo( 19.2.1.1²'⁵.1⁷'¹⁰)hexacosa-2(26),3,5,7,9,21 ,23-heptaene, or a pharmaceutically acceptable salt thereof. For use in the present methods for inhibiting the replication or infectivity of a virus, a prefened subclass of the compounds of Formula (IN) is that wherein, in the compound of Formula (IV):

For use in the present methods for inhibiting the replication or infectivity of a virus, a second prefened subclass of the compounds of Formula (IV) is that wherein, in the compound of Formula (IN): R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

R_s is -H; and p is an integer of 6 or 8.

For use in the present methods for inhibiting the replication or infectivity of a virus, a third prefened subclass of the compounds of Formula (IV) is that wherein, in the compound of Formula (TV) :

R₂ is selected from the group consisting of -CH₂CH₃, and -CH₂C₆H₅;

For use in the present methods for inhibiting the replication or infectivity of a virus, a fourth prefened subclass of the compounds of Formula (IN) is that wherein, in the compound of Formula (IN):

Rg is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and p is an integer ranging from 6 to 8.

4.5. FORMULA V

or a pharmaceutically acceptable salt thereof, wherein:

R, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_πR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₇ is selected from the group consisting of -H, C,-C₁₅ straight chain alkyl, -(CH₂)₉CH=CH₂, -(CH₂)₆F, -(CH₂)₅OC₆H₅, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₆H₅, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)_nCOOH, -(CH₂)₁₂COOH, -(CH₂)_I2OH, -(CH₂)₁₃OH, -(CH₂)_nCN, -(CH₂)„OC(O)NH₂, -(CH₂)_U COOEt, -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, C₃-C₇ cycloalkyl, -C₆H₅, 2-pynolyl, -3-pynolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, and 3-fiiranyl, the phenyl being substituted with one or more halo, methyl, methoxyl, hydroxyl, methoxycarbonyl or trifluoromethyl groups;

R_g is selected from the group consisting of -H, C,-C,, straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, then Re, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then R, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅; R,, and R,₂ are independently selected from the group consisting of -CH₃, -CH₂CH₃, and -C₃H₇;

R₁₆ is selected from the group consisting of -H, -CH₃, -CH₂CH₂CH₃, and -(CH₂)₆CH₃; and R_I7 is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and

-COOH; with the proviso that the compound of Formula (V) is not: prodigiosin, undecylprodigiosin, norprodigiosin, or nonylprodigiosin.

Where R₇ is phenyl substituted with one or more halo, -CH₃, -OCH₃, -OH, -COOCH₃, or -CF₃ groups, R₇ is preferably 4-methylphenyl, 4-methoxyphenyl, 4- hydroxyphenyl, 4-(methoxycarbonyl)phenyl, 4-(trifluoromethyl)phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 2,4-dimethoxyphenyl, 2,4-dichlorophenyl, and 2-chloro-4-fluorophenyl.

Prefened compounds for use in the methods for treating or preventing cancer or a neoplastic disease are:

6-methoxy-2-methyl-3-heptylprodigeosene, 4-methoxy-5-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-2,2'-bi- lH-pynol, nonylprodigiosin, and 3-heptyl-5-((3-methoxy-5-pynol-2-yl-2H-pynol-2- ylidene)methyl)-2-methyl-4-propylpynole, or pharmaceutically acceptable salts thereof.

For use in the present methods for treating or preventing cancer or a neoplastic disease, a prefened subclass of the compounds of Formula (V) is that wherein, in the compound of Formula (V):

R is -H;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH(CH₃)₂, and -CH₂C₆H₅;

R₇ is selected from the group consisting of -H, -C,-C₁₅ straight chain alkyl, -(CH₂)₉C=CH₂, -(CH₂)₅CH₂F, -(CH₂)₅OC₅H₆, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₅H₆, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂)₁₂COOH, -(CH₂)₁₂OH, -(CH₂)₁₃OH, -(CH₂)„CN, -(CH₂)_nOC(O)NH₂, -(CH₂)„COOEt -C(O)(CH₂)₉CH₃, -(CH₂)_sC(O)N(CH₂CH₂)₂O, and 2-pynolyl;

R_g is selected from the group consisting of -H, C,-C_π straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃; R_I6 is selected from the group consisting of -H, -CH₃, -CH₂CH₂CH₃, and

-(CH₂)₆CH₃; and

For use in the present methods for treating or preventing cancer or a neoplastic disease, a second prefened subclass of the compounds of Formula (V) is that wherein, in the compound of Formula (V):

R, is -H;

R₂ is selected from the group consisting of C,-C,₂ straight chain alkyl, -CH(CH₃)₂, and -CH₂C₆H₅; R₇ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₈-C,₅ straight chain alkyl, -(CH₂)₉C=CH₂, -(CH₂)₅CH₂F, -(CH₂)₅OC₅H₆, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₅H₆, -(CH₂)₄COOH, -(CH₂)₅COOH, --(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂)₁₂COOH, -(CH₂)₁₂OH, -(CH₂)_!3OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)„COOEt -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, and 2-pynolyl; R_g is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₆-C,, straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, Re, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R_I7 is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH; with the proviso that the compound of Formula (V) is not: prodigiosin, or undecylprodiginine.

The present invention provides methods for inhibiting the growth of a cancer cell or neoplastic cell comprising a contacting a cancer cell or neoplastic cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (V) or a pharmaceutically acceptable salt thereof, wherein:

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R„R,₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₇ is selected from the group consisting of -H, C,-C,₅ straight chain alkyl, -(CH₂)₉CH=CH₂, -(CH₂)₆F, -(CH₂)₅OC₆H₅, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₆H₅, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂)₁₂COOH, -(CH₂)₁₂OH, -(CH₂)₁₃OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)_πCOOEt, -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, C₃-C₇ cycloalkyl, -C₆H₅, 2-pynolyl, -3-pynolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-fiιranyl, and 3-furanyl, the phenyl being substituted with one or more halo, methyl, methoxyl, hydroxyl, methoxycarbonyl or trifluoromethyl groups; R₈ is selected from the group consisting of -H, C_j-C_π straight chain alkyl,

-(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, R_j is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Re, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R,, and R,₂ are independently selected from the group consisting of -CH₃, -CH₂CH₃, and -C₃H₇; R₁₆ is selected from the group consisting of -H, -CH₃, -CH₂CH₂CH₃, and

-(CH₂)₆CH₃; and

R_I7 is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH; with the proviso that the compound of Formula (V) is not: prodigiosin, undecylprodigiosin, norprodigiosin, or nonylprodigiosin. Prefened compounds for use in the method for inhibiting the growth of a cancer or neoplastic cell are:

6-methoxy-2-methyl-3-heptylprodigeosene,

4-methoxy-5-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-2,2'-bi- lH-pynol, nonylprodigiosin, and 3-heptyl-5-((3-methoxy-5-pynol-2-yl-2H-pynol-2- ylidene)methyl)-2-methyl-4-propyl-pynole, or a pharmaceutically acceptable salt thereof. For use in the present methods for inhibiting the growth of a cancer or neoplastic cell, a prefened subclass of the compounds of Formula (V) is that wherein, in the compound of Formula (V):

R, is -H;

R₇ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₃-C₁₅ straight chain alkyl, -(CH₂)₉CH=CH₂, -(CH₂)₅CH₂F, -(CH₂)₅OC₆H₅, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₆H₅, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂)₁₂COOH, -(CH₂)₁₂OH, -(CH₂)₁₃OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)„COOEt -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, and 2-pynolyl;

R_g is selected from the group consisting of -H, C,-C,, straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then R_<* is selected from the group consisting of -H, -CH₃,

-CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R₁₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH; with the proviso that the compound of Formula (V) is not: prodigiosin, undecylprodigiosin, norprodigiosin, or nonylprodigiosin. For use in the present methods for inhibiting the growth of a cancer or neoplastic cell, a second prefened subclass of the compounds of Formula (V) is that wherein, in the compound of Formula (V): R, is -H; R₂ is selected from the group consisting of -CH₃, C,-C₁₂ straight chain alkyl,

-CH(CH₃)₂, and -CH₂C₆H₅;

R₇ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₈-C,₅ straight chain alkyl, -(CH₂)₉CH=CH₂, -(CH₂)₅CH₂F, -(CH₂)₅OC₆H₅, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₆H₅, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂)₁₂COOH, -(CH₂)₁₂OH, -(CH₂)₁₃OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)_nCOOEt -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, and 2-pynolyl;

R_g is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₆-C_π straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R₁₆ is selected from the group consisting of -H, -CH₃, -CH₂CH₂CH₃, and -(CH₂)₆CH₃; R₁₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and

-COOH; with the proviso that the compound of Formula (V) is not: prodigiosin, or undecylprodiginine. The present invention provides methods for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (V) or a pharmaceutically acceptable salt thereof, wherein: R. is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅,

-C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R..R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; R₇ is selected from the group consisting of -H, C,-C,₅ straight chain alkyl, -(CH₂)₉CH=CH₂, -(CH₂)₆F, -(CH₂)₅OC₆H_s, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₆H₅, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂),₂COOH, -(CH₂)₁₂OH, -(CH₂)₁₃OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)„ COOEt, -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, C₃-C₇ cycloalkyl, -C₆H₅, 2-pynolyl, -3-pynolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, and 3-furanyl, the phenyl being substituted with one or more halo, methyl, methoxyl, hydroxyl, methoxycarbonyl or trifluoromethyl groups;

Rg is selected from the group consisting of -H, C,-C_u straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃; R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R,, and R₁₂ are independently selected from the group consisting of -CH₃, -CH₂CH₃, and -C₃H₇;

R_I7 is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH.

Prefened compounds for use in the methods for treating or preventing a viral infection are: 6-methoxy-2-methyl-3-heptylprodigeosene, 4-methoxy-5-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl) 2, 2'-bi- lH-pynol, nonylprodigiosin,

3-heptyl-5-((3-methoxy-5-pynol-2-yl-2H-pynol-2-ylidene)methyl)-2-methyl-4- propyl-pynole, prodigiosin, undecylprodigiosin, norprodigiosin, and nonylprodigiosin, or pharmaceutically acceptable salts thereof. For use in the present methods for treating or preventing a viral infection, a prefened subclass of the compounds of Formula (V) is that wherein, in the compound of Formula (V):

R, is -H; R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl,

-CH(CH₃)₂, and -CH₂C₆H₅;

R₇ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₃-C,₅ straight chain alkyl, -(CH₂)₉CH=CH₂₎ -(CH₂)₅CH,F, -(CH₂)₅OC₆H₅, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₆H₅, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂),₂COOH, -(CH₂)₁₂OH, -(CH₂)₁₃OH, -(CH₂)„CN, -(CH₂)₁₁OC(O)NH₂, -(CH₂)„COOEt -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, and 2-pynolyl;

R₈ is selected from the group consisting of -H, C,-C,, straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R,₆ is selected from the group consisting of -H, -CH₃, -CH₂CH₂CH₃, and -(CH₂)₆CH₃; and R₁₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and

-COOH.

For use in the present methods for treating or preventing a viral infection, a second prefened subclass of the compounds of Formula (V) is that wherein, in the compound of Formula (V): R. is -H;

R₂ is selected from the group consisting of C,-C₁₂ straight chain alkyl, -CH(CH₃)₂, and -CH₂C₆H₅;

R₇ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₈-C,₅ straight chain alkyl, -(CH₂)₉CH=CH₂, -(CH₂)₅CH₂F, -(CH₂)₅OC₆H₅, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₆H₅, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH,

-(CH₂)₁₂COOH, -(CH₂)₁₂OH, -(CH₂)₁₃OH, -(CH₂)„CN, -(CH₂)_nOC(O)NH₂, -(CH₂)„COOEt -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, and 2-pynolyl;

R_g is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₆-C_π straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃; R₁₆ is selected from the group consisting of -H, -CH₃, -CH₂CH₂CH₃, and

-(CH₂)₆CH₃; and

R. is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR,₀R_πR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₇ is selected from the group consisting of -H, C,-C,₅ straight chain alkyl, -(CH₂)₉CH=CH₂, -(CH₂)₆F, -(CH₂)₅OC₆H₅, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₆H₅, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂),₂COOH, -(CH₂)₁₂OH, -(CH₂)₁₃OH, -(CH₂)„CN, -(CH₂)_πOC(O)NH₂, -(CH₂)„COOEt, -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, C₃-C₇ cycloalkyl, -C₆H₅, 2-pynolyl, -3-pynolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, and 3-furanyl, the phenyl being substituted with one or more halo, methyl, methoxyl, hydroxyl, methoxycarbonyl or trifluoromethyl groups;

R_g is selected from the group consisting of -H, C,-C_n straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl

R_π and R₁₂ are independently selected from the group consisting of -CH₃, -CH₂CH₃, and -C₃H₇;

R₁₆ is selected from the group consisting of -H, -CH₃, -CH₂CH₂CH₃, and -(CH₂)₆CH₃; and R₁₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and

-COOH.

6-methoxy-2-methyl-3-heptylprodigeosene, 4-methoxy-5-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-2,2'-bi- lH-pynol, nonylprodigiosin,

3-heptyl-5-((3-methoxy-5-pynol-2-yl-2H-pynol-2-ylidene)methyl)-2-methyl-4- propyl-pynole prodigiosin, undecylprodigiosin, norprodigiosin, and nonylprodigiosin, or pharmaceutically acceptable salts thereof. For use in the present methods for inhibiting the replication or infectivity of a virus, a prefened subclass of the compounds of Formula (V) is that wherein, in the compound of Formula (V):

R, is -H;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH(CH₃)₂, and -CH₂C₆H₅; R₇ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₃-C,_s straight chain alkyl, -(CH₂)₉C=CH₂, -(CH₂)₅CH₂F, -(CH₂)₅OC₅H₆, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₅H₆, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂),₂COOH, -(CH₂),₂OH, -(CH₂)₁₃OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)„COOEt, -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, and 2-pynolyl; Rg is selected from the group consisting of -H, C,-C,, straight chain alkyl,

-(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃; R₁₆ is selected from the group consisting of -H, -CH₃, -CH₂CH₂CH₃, and -(CH₂)₆CH₃; and

R₁₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH. For use in the present methods for inhibiting the replication or infectivity of a virus, a second prefened subclass of the compounds of Formula (V) is that wherein, in the compound of Formula (V):

R* is -H;

R₂ is selected from the group consisting of C,-C,₂ straight chain alkyl, -CH(CH₃)₂, and -CH₂C₆H₅;

R₇ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₈-C₁₅ straight chain alkyl, -(CH₂)₉0=CH₂, -(CH₂)₅CH₂F, -(CH₂)₅OC₅H₆, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₅H₆, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂)₁₂COOH, -(CH₂)_I2OH, -(CH₂)₁₃OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)„COOEt - C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, and 2-pynolyl;

R₈ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₆-C,, straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, R, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃,

-CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

4.6. RACEMATES AND ENANTIOMERS OF FORMULA (I-V) COMPOUNDS

As used herein, the term "Pynole-Type compounds" means, collectively, the compounds of Formulas (I-V) and racemates and/or enantiomers thereof, and pharmaceutically acceptable salts thereof. I

4.7. SYNTHESIS OF THE PYRROLE-TYPE COMPOUNDS

The compounds of the invention can be obtained via conventional organic syntheses, e.g., as described below. Schemes A-I indicate methods by which compounds of the invention may be obtained. In several sections herein and within Schemes A-I, chemical classes are indicated by numerical labeling in bold text.

4.7.1. THE COMPOUNDS OF FORMULA (I)

The compounds of Formula (I) can be obtained using conventional organic synthesis or by the following illustrative methods: The compounds of Formula (I) wherein R, is H, R₂ is Me, R₃ is straight chain alkyl, benzyl or substituted benzyl, and m is 1-5 can be prepared by the methods shown in Scheme A.

Scheme A cont.

LiAIH₄

Specifically, the dipynole aldehyde 1 (D.L. Boger and M. Patel, J. Org. Chem. 53, 1405- 1415, 1988) reacts under acid catalysis with the pynole 2, giving the prodigiosene 3. The reaction of 1 with pynoles, such as 2, is also carried out with phosphorous oxychloride in solvents such as pentane. (J.A. van Koeveringe and J. Lugtenburg, Reel. Trav. Chim. Pays- Bas 96, 55-58, 1977.)

The methods used for the synthesis of pynoles of structure 2 are outlined in Scheme A. R₁₄ is R₃ less its α-carbon. These methods have been described by A. Fϋrstner et al., J. Am. Chem. Soc. 120, 8305-8314, 1998; when m is 1 and R₁₄ is «-C₃H₇, the structure 3 compound produced is butylcycloheptylprodigiosin (also know as streptorubin B or butyl- meta-cycloheptylprodigiosin). Compounds 2 where m is 2 - 5 are prepared by replacing cis-cyclooctene (4, m = 1) with cw-cyclononene, cz^'s-cyclodecene, c/s-cycloundecene, and cw-cyclododecene (m = 2, 3, 4, and 5, respectively). The structure of the R₃ group (straight chain alkyl, benzyl, substituted benzyl, or 2-, 3-, or 4-pyridyl) in compounds 2 is determined by the choice of the acid chloride 8 used in the reaction with compound 7. Thus, for example, the compound 2 in which m is 1 and R₁₄ is C₆H₅ is produced when czs-cyclooctene (4, m is 1) and benzoyl chloride (8, R₁₄ is C₆H₅) are used at the appropriate points of the synthesis. Acid chlorides are prepared from their conesponding carboxylic acids by using thionyl chloride, oxalyl chloride, and/or other methods known in the art.

Compounds of Formula (I) wherein R, is H, R₂ is Me, and R₃ is an acyl group as defined above can be prepared by the methods shown in Scheme B.

Scheme B cont.

Scheme B cont.

Variations of m and R,₄ are introduced as described above. The ketone functionality of compound 11 is converted to the dimethyl ketal 15 by methods well known in the art (see, for example, T.W. Greene and P.G.M. Wuts, "Protective Groups in Organic Synthesis," 2^nd Ed., Wiley, New York, 1991, pp 178-183. ( "Greene and Wuts."). The N-Ts-dihydropynole ring of 15 is converted to the pynole 16 by the method of Fϋrstner et al., cited above. The ketone carbonyl group is regenerated by standard methods, giving the acyl compound 17. The compound 17 reacts with 1 under conditions given above to produce the acylprodigiosene 18.

Compounds of Formula (I) wherein R, is H, R₂ is Me, and R₃ is a 1-hydroxyalkyl group are prepared from 18 as shown in Scheme B. Using standard hydride reduction methods, such as sodium borohydride, 19 is obtained from 18.

Compounds of Formula (I) wherein R, is H, R₂ is Me, and R₃ is a branched alkyl are prepared by the methods shown in Scheme B. R,₅ is the branch of the branched chain alkyl. The ketopynole 17 reacts with sodium hydride and phenyl t-butylcarbonate (Greene and Wuts, p. 387), giving the N-BOC-pynoIe 20. Compound 20 is reacted with an alkyl (R₁₅) magnesium iodide in a Grignard reaction, giving tertiary alcohol 21. In a series of well- known reaction steps, 21 is converted to the branched alkyl pynole derivative 23. First the hydroxyl group of 21 is replaced with iodide by reaction with hydrogen iodide. The iodine atom is removed from 22 by hydride reduction, for example, with sodium borohydride. The

N-BOC protecting group is removed using trifluoroacetic acid and the resulting pynole 23 reacts with 1 under conditions given above, giving the branched alkyl compound 24. Thus, for example, the compound 24 in which m is 1 and R,₄ and R₁₅ are Me is produced when 8 is acetyl chloride (Scheme A) and R_I5 Mgl is methyl magnesium iodide.

Compounds of Formula (I) wherein R, is H, R₂ is Me, and R₃ is a 1-chloroalkyl group are prepared by the methods shown in Scheme B. The ketone carbonyl of 20 is reduced with, for example, sodium borohydride, giving the hydroxyl compound 25.

Reaction of 25 with thionyl chloride replaces the hydroxyl group with a chlorine atom as shown in 26. The N-BOC protecting group is removed as described above to give the pynole 27, which reacts with 1 to give 28.

Compounds of Formula (I) wherein R, is H, R₂ is Me, and R₃ is a hydrogen atom are prepared by the methods shown in Scheme C.

<u

X u. Scheme C cont.

Bu₃SnH AIBN

Compound 1 where R₁₄ is Me, undergoes a Baeyer-Villiger reaction and thereby is converted to the acetoxy derivative 29. The acetoxy group is saponified by methods known to the art, giving the hydroxyl derivative 30. Using methodology of Ftirstner et al., outlined above, the hydroxyl group of 30 is removed in the series of reactions shown in Scheme C leading to 33 via 31 and 32. Finally, the reaction of 33 with 1 under acid catalysis as described above gives 34.

Compounds of Formula (I) wherein R, is H, R₂ is Me, and R₃ is a methyl group are prepared by the methods shown in Schemes A and C. Using ethyl chloroformate (in compound 8, R,₄ is OEt) in reaction with 7 (Scheme A), one obtains 9, which is converted to 11 using the reaction conditions outlined in Scheme A. The compound 11 is reduced with, for example, lithium aluminum hydride, giving the hydroxymethyl derivative 35 (Scheme C). Using the same series of reactions described above, 35 is transformed into the methyl-substituted pynole 38 via 36 and 37 which, in turn, reacts with 1 under acid catalysis, furnishing 39.

Once the tompounds of Formula (I) have been synthesized, they can be purified or substantially purified, using conventional chromatography, recrystallization or other purification techniques known to those skilled in the art.

In certain embodiments of the invention, the compounds of the invention are indicated by chemical name. The structures of these compounds are indicated in Table 3, below, which describes the structure as shown in the conesponding synthesis Schemes. Table 3

FORMULA I

Compound Structure

2-(2-Hydroxy-n-butyl)- 11 -((3-methoxy-5- chemical class 19 as depicted in Scheme B; (lH-pynol-2-yl)-2H-pynol-2- R₁₄ is -CΗ₂CΗ₂CΗ₃, m is 1 ylidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene

2-(2-Chloro-«-butyl)-l l-((3-methoxy-5- chemical class 24 as depicted in Scheme B; (lH-pynol-2-yl)-2H-pynol-2- R₁₄ is-CΗ₂CΗ₂CΗ₃, m is 1 ylidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene

2-Butyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)- Formula I; R, is -Η, R₂is -CΗ₂CΗ₃, 2H-pynol-2-ylidene)methyl)- 10- R₃ is -(CH₂)₃CH₃, R₁₆ is -H, R₁₇ is -H, m is 1 azabicyclo[7.2.1]dodeca-9(12),l 1-diene

11 -((3-Ethoxy-5-(lH-pynol-2-yl)-2H- Formula I; R, is -Η, R₂ is -CΗ₂CΗ₃, R₃ is - pynol-2-ylidene)methyl)- 10- H, R,₆ is -H, R_I7 is -H, m is 1 azabicyclo[7.2.1]dodeca-9(12),l 1-diene

2-Methyl-ll-((3-ethoxy-5-(lH-pynol-2- Formula I; R, is -Η, R₂ is -CΗ₂CΗ₃, yl)-2H-pynol-2-ylidene)methyl)- 10- R-, is CH,, R,_Λ is -H, R,₇ is -H, m is 1 azabicyclo[7.2.1]dodeca-9(12),l 1-diene

2-n-Proρyl-l l-((3-ethoxy-5-(lH-ρynol-2- Formula I; R, is -Η, R₂ is -CΗ₂CΗ₃, yl)-2H-pynol-2-ylidene)methyl)- 10- R₃ is -(CH₂)₂CH₃, R,₆ is -H, R,₇ is -H, m is 1 azabicyclo[7.2.1]dodeca-9(12),l 1-diene

2-n-Pentyl-l 1 -((3-ethoxy-5-(lH-pynol-2- Formula I; R, is -Η, R₂ is -CΗ₂CΗ₃, yl)-2H-pynol-2-ylidene)methyl)- 10- R₃ is -(CH₂)₄CH₃, R,₆ is -H, R₁₇ is -H, m is 1 azabicyclo[7.2.1]dodeca-9(12),l 1-diene

2-Benzyl-ll-((3-ethoxy-5-(lH-pynol-2- Formula I; R, is -Η, R₂ is -CΗ₂CΗ₃, yl)-2H-pynol-2-ylidene)methyl)- 10- R₃ is -CH₂C₆H₅, R₁₆ is -H, R,₇ is -H, m is 1 azabicyclo[7.2.1]dodeca-9(12),l 1-diene

2-Ethyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)- Formula I; R, is -Η, R, is -CΗ,CΗ ₃' 2H-pynol-2-ylidene)methyl)- 10- R₃ is -CH₂CH₃, R₁₆ is -H, R₁₇ is -H, m is 1 azabicyclo[7.2.1]dodeca-9(12),l 1-diene

4.7.2. THE COMPOUNDS OF FORMULA (ID

The compounds of Formula (II) can be obtained using conventional organic synthesis or by the following illustrative methods: Compounds of Formula (II) where R, is H and R₂ is Me can be prepared by the methods shown in Scheme D.

<

0)

Λ u CO The dipynole aldehyde 1 reacts under acid catalysis with the pynole of structure 40 giving the prodigiosene 41. Pynoles of structure 40 are prepared starting with the appropriate α- substituted cycloalkanone 42. The reaction of 42 with 2,4,6-tri-i- propylphenylsulfonylhydrazme gives the conesponding hydrazone 43. Compound 43 reacts with sec-butyllithium and N,N-dimethyIformamide (DMF) to give the α,β-unsaturated aldehyde 44. The anion of the dimethylthioacetaldehyde reagent 45 is generated using «-butyllithium and adds to the conjugated system of 44, producing 46. The group R₄ in 45 may be hydrogen or C,-C,₂ alkyl. Reaction of 46 with mercury(II) chloride and calcium carbonate converts the dimethylthiocarbonyl into a carbonyl group, generating 47. Compound 47 reacts with ammonium carbonate in DMF giving the pynole 40. The methods shown in Scheme D for the chemical transformation of compound 42 into compound 40 have been described by H.H. Wasserman and J.M. Fukuyama, Tetrahedron Lett. 25, 1387-1388, 1984. When in compound 42, n is 2 and R₅ is Me, and when in compound 45, R₄ is Me, then the structure 40 is cycloprodigiosin as described by

Wasserman and Fukuyama. Compounds of structure 42 useful in the reaction sequence of Scheme D include, but are not limited to, cyclopentanone, cyclohexanone, cycloheptanone, cyclooctanone, cyclononanone, cyclodecanone and the 2-methyl and 2-ethyl derivatives of each of these cyclic ketones. The dimethylthioacetals 45 are prepared from their conesponding aldehydes by methods well known in the art and are chosen to give the range of alkyl substituents specified above.

Once the compounds of Formula (II) have been synthesized, they can be purified or substantially purified, using conventional chromatography, recrystallization or other purification techniques known to those skilled in the art. fn certain embodiments of the invention, the compounds of the invention are indicated by chemical name. The structures of these compounds are indicated in Table 4, below, which describes the structure as shown in the conesponding synthesis Schemes. Table 4

4.7.3. THE COMPOUNDS OFFORMULA (III)

The compounds of Formula (HI) can be obtained using conventional organic synthesis or by the following illustrative methods: Compounds of Formula (III) where R, is H and R₂ is Me can be prepared by the methods shown in Scheme E.

<u s o o Scheme E cont.

54 51 55 56

HJ eOH

58 57

The dipynole aldehyde 1 reacts under acid catalysis with the pynole of structure 48 giving the prodigiosene 49. Pynoles of structure 48 are prepared starting with the appropriate cyclic ketone 50 as outlined in Scheme E. The cyclic ketone 50 reacts with O-(2- r hydroxyethyl)-hydroxylamine 51 (D. Dhanak et al., J. Chem. Soc, Chem. Commun. 903- 904, 1986) forming the O-(2-hydroxyethyl)-oxime 52. The hydroxyl group of 52 is replaced with iodine by reaction with methyltriphenoxyphosphonium iodide, giving 53. Cyclization of 53 occurs upon heating with potassium t-butoxide in t-butyl alcohol and affords the pynole 48. Compounds of structure 50 that are used to prepare compounds of structure 48 O include, but are not limited to, cyclopentanone; cyclohexanone; 2- methyl-, 2-ethyl-, 4-methyl-, 4-ethyl-, 4-propyl-, 4-n-butyl, and 4-phenylcyclohexanone; cycloheptanone; 2-methyl- and 2-ethylcycloheptanone; cyclooctanone; 2-methyl-, 2-ethyl-, 5-methyl-, and 5-ethylcyclooctanone; cyclononanone; 2-methyl- and 2-ethylcyclononanone; cyclodecanone; 2-methyl-, 2-ethyl-, 6-methyl-, and 6-ethylcyclodecanone. When, for 5 example, 4-methylcyclohexanone 54 is used in this series of reactions, the oxime 55 is first formed. From 55 the iodide 56 is prepared and is cyclized to the pynole 57. Reaction of 57 with 1 gives the prodigiosene 58.

Once the compounds of Formula (IH) have been synthesized, they can be purified or substantially purified, using conventional chromatography, recrystallization or other

20 purification techniques known to those skilled in the art.

In certain embodiments of the invention, the compounds of the invention are indicated by chemical name. The structures of these compounds are indicated in Table 5, below, which describes the structure as shown in the conesponding synthesis Schemes. Table 5

25

30

35 4.7.4. THE COMPOUNDS OF FORMULA (IV)

The compounds of Formula (IV) can be obtained using conventional organic synthesis or by the following illustrative methods:

Compounds of Formula (IV) where R, is H and R₂ is Me can be prepared by the methods shown in Scheme F.

<w

<u u Scheme F cont.

The O-TMS-bromoalcohol 59 reacts with pyrrylmagnesium bromide 60 giving the 2- substituted pynole 61. The pynole 61 reacts with t-butyloxycarbonyl anhydride (BOC anhydride) to give the N-BOC-pynole 62. The O-TMS protecting group is removed in acetic acid- water, giving the alcohol 63. The alcohol 63 is converted to the O-mesylate 64, and the mesylate group is replaced with bromine, giving 65. The alkyl bromide 65 reacts with 60, giving 66. A Vilsmeier reaction with 66 introduces a carboxaldehyde group into the α-position of the pynole ring that is not N-BOC protected. The carboxaldehyde 67 reacts (R. D'Alessio and A. Rossi, SYNLETT 513-514, 1996) with 5H-4-methoxypynol- 2(lH)-one 68 (L; Due, etal., Synthesis 391-394, 1992) under alkaline conditions. The N-BOC group lost in this reaction is replaced, giving 69. The boronic acid group of 70 is introduced (D'Alessio and Rossi) and the carbonyl group of the pynol-2-one functionality is converted to an O-triflate group, giving 71. Reaction of 71 in the presence of Pd(0) generates the prodigiosene 72. The bromoalcohols used for the preparation of compounds of structure 59 include, but are not limited to, 8-bromononan-l-ol, 8-bromodecan-l-ol, 9-bromodecan-l-ol, 9-bromoundecan-l-ol, 10-bromoundecan-l-ol, and 10-bromododecan-l-ol. The O-TMS derivatives, obtained from bromoalcohols, are prepared by methods known to the art. Compounds of Formula (IN) are also prepared by adaptations of methods described by Fϋrstner et al., 1999 J. Org. Chem. 64:8275-8280. Once the compounds of Formula (IN) have been synthesized, they can be purified or substantially purified, using conventional chromatography, recrystallization or other purification techniques known to those skilled in the art.

In certain embodiments of the invention, the compounds of the invention are indicated by chemical name. The structures of these compounds are indicated in Table 6, below, which describes the structure as shown in the conesponding synthesis Schemes. Table 6

4.7.5. THE COMPOUNDS OF FORMULA CV)

The compounds of Formula (V) can be obtained using conventional organic synthesis or by the following illustrative methods:

Compounds of Formula V where R, is H and R₂ is Me can be prepared by the methods shown in Scheme G.

cu

-S u cc Scheme G cont.

Scheme G cont.

TsNHCH₂Ts

Scheme G cont.

The dipynole aldehyde 1 reacts under acid catalysis with the pynole of structure 73 giving the prodigiosene 74. Numerous methods have been described for the synthesis of pynoles of structure 73 (e.g., G.P. Bear, "The Synthesis of lH-Pynoles" in "Pynoles," Vol. 1, R.A. Jones, ed., Wiley, N.Y., 1990; pp 105-294). For pynoles 73 where R₇ is alkyl or cycloalkyl and R₈ is R, is Η, reaction of the pynole Grignard reagent 60 with an alkyl halide or cycloalkyl halide gives the desired 2-substituted pynole 75. The 2-substituted pynoles 75 are further substituted in the 3 -position by the sequence of reactions showing the transformation of 75 into 80 in Scheme G and adapted from the report by A.J. Castro et.al, J- Org. Chem. 28, 857-860, 1963. In this reaction sequence, the reagent 78 is chosen so that R₁₆ is one methylene group shorter than R₇ of the final pynole. The two steps shown in Scheme G by which 77 is converted to 80, i.e., acylation of the pynole ring - in this case by a Friedel-Crafts type process - followed by a Wolff-Kishner type reduction, are of general use for the introduction of acyl and/or alkyl and aralkyl groups onto the pynole nucleus. Another acylation method widely used with pyrroles is the Vilsmeier process, described above and illustrated in Scheme F in the conversion of compound 66 to 67 (e.g., D.O.A. Garrido et al., J. Org. Chem. 49, 2619-2622, 1984). Replacement of dimethylformamide by other dimethylalkyl or arylamides in the Vilsmeier process introduces an acyl group into the pynole. The method of Dhanak et al, described above, is also useful for the synthesis of pynoles of structure 73 in which R₇ is one carbon length shorter than R₈ and R^ is Η when symmetrical alkyl ketones are used as a starting material. A large variety of 2,3- disubstituted pynoles (where R₇ and R_g are non-hydrogen substituents and R_<, is Η) are prepared by methods reported by Severin and coworkers (see Pynoles, Vol. 1; pp 159-161 and references cited therein). The ketone 81 and glyoxalhydrazone 82 condense, giving 83, which cyclizes to the pynole 84 when reacted with either sodium dithionite or zinc. The intermediate 83 also reacts with titanium trichloride to provide a 1,4-ketoaldehyde 85, which reacts with ammonium acetate or a primary amine to yield the pynole 86. Reaction of TsNΗCΗ₂Ts with 87 under alkaline conditions (H. Kinoshita et al., Chem. Lett. 1033- 1036, 1986; CA. 106:84139d) gives an intermediate addition product that under acidic conditions is converted to the N-tosylpynole 88. Removal of the tosyl group from 88 by standard methods affords the 3-substituted pynole 89 that is used in the synthesis of prodigiosenes. For example, in pynole 89, when R_g is -(CH₂)₁₀CH₃, and R₇ and Re, are H, reaction with 1 gives prodigiosene 90. Among the methods for preparation of 2,4-disubstituted, 3,4-disubstituted, and 2,3,4-trisubstituted pynoles are those described by J. Tang above; J.G. Verkade, J. Org. Chem. 59, 7793-7802, 1994; B. Franck et al., Liebigs _

Ann. Chem. 503-510, 1994; D. Brown et al, J. Chem. Soc. Perkin Trans. 1, 455-463, 1986;

D. Enders et al., Tetrahedron Lett. 36, 8007-8010, 1995; and K. Utimoto et al., Tetrahedron

Lett. 22, 4277-4278, 1981. Reaction of, for example, the 2,4-disubstituted pynole 91 with 1 , gives the prodigiosene 92. Reaction of the 3,4-disubstituted pynole 93 with 1 gives the prodigiosene 94. Reaction of the 2,3,4-trisubstituted pynole 95 with 1 gives the prodigiosene 96. The preparations of furyl-substituted pynoles have been described in the literature, for example by Korostova et al., Zh. Org. him. 30, 905-908, 1994 (CA.

122:290633k); LG. Iovel et al, Khim. Geterotsikl. Soedin., 746-749, 1989 (CA. ₁₀ 112: 178533v); S.E. Korostova et al., Khim. Geterotsikl. Soedin., 901-906, 1989 (CA.

112:178530s); A.M. Nadim et al., Khim. Geterotsikl. Soedin., 1141-1143, 1991 (CA.

116:194084n); MN. Sigalov et al., J. Org. Chem. 57, 3943-3948,1992 and references cited therein. Furyl pynoles, for example 97, react with 1, giving the prodigiosenes, in this case

98. _j 5 Once the compounds of Formula (V) have been synthesized, they can be purified or substantially purified, using conventional chromatography, recrystallization or other purification techniques known to those skilled in the art.

4.7.6. OTHERCOMPOUNDS OFFORMULA (I-V>

20 The compounds of Formulas I - III and V in which R, is not H are prepared using methods shown in Scheme H.

25

30

35

w

Λ <υ C Scheme H cont.

Scheme H cont.

Scheme H cont.

The bipynole carboxylic ester 99 reacts with iodides 100, such as methyl iodide, ethyl iodide and benzyl iodide, in the presence of a base such as pyridine, triethylamine, or sodium carbonate or in the presence of one equivalent of a base such as «-butyllithium or _t- potassium t-butoxide, generating 101. Hydrazino lysis of 101 converts the carboxylic acid ester into the hydrazide 102. The hydrazide is tosylated with/?-toluenesulfonyl chloride, giving 103, which reacts with sodium carbonate to give the aldehyde 104 (R, is Me). The synthesis of compound 99 has been described by Boger and Patel, cited above. The three- step reaction sequence used for conversion of carboxylate esters into aldehydes also is ι o described by Boger and Patel and was originally reported by H. Rapoport and K.G. Holden, J. Am. Chem. Soc. 84, 635-642, 1962. The reaction of 104 (R, is Me) with, for example, 105 where m is 1 and R,₄ is «-C₃H₇ under acid catalysis generates the prodigiosene 106 (R,₄ is R₃ less its α-carbon). Pynoles such as those described herein having no substituent on the nitrogen atom are N-alkylated or N-acylated by methods known to the art. The reaction of 5 104 (R, is Me) with the N-alkylated or acylated pynole 107 where, for example, R, is Me, gives the prodigiosene 108 under acidic conditions. The reaction of 1 with 107 likewise produces the prodigiosene 109 wherein the ring-A pynole has an unsubstituted N-H atom and the ring-C pynole is N-Me substituted. Other examples, which are intended to illustrate but not to limit the methods by which prodigiosenes with R₂ is not Me are prepared, are also

20 shown in Scheme H. Reaction of 104 (R, is -CH₂Ph) with pynole 110 (R, is -CH₂Ph) gives the prodigiosene 111. The reaction of 104 (R, is Me) with the pynole 112 (R, is BOC) gives the prodigiosene 113. The reaction of 104 (R, is Me) with the pynole 114 (R, is Me) gives the prodigiosene 115.

The compounds of Formulas I - V in which R₂ is not Me can be prepared using

25 methods shown in Scheme I.

30

35

<υ CC Scheme I cont.

Scheme I cont.

The methoxyl group (at R₂) of the compound of Formula I, II, III, IV, or V is demethylated with boron tribromide, iodotrimethylsilane, sodium ethylthiolate, or other reagents (Greene and Wuts, pp. 145-149). For example, reaction of the prodigiosene 116 with BBr₃ gives the hydroxy compound 117. Reaction of 117 with an alkyl >-toluenesulfonate such as ethyl p- toluenesulfonate, benzyl 7-toluenesulfonate, or substituted benzyl /7-toluenesulfonate in dimethylimidazolidinone (DMI) generates alkyl ether 119 (Pynoles, Part 2, R.A. Jones, Ed., Wiley, N.Y., 1992; p. 557; G.A. Hunter, etal., J. Chem. Soc. Perkin Trans. 1, 3245-3251, 1991). Another example is the cleavage of the methyl ether of prodigiosene 120 followed by re-etherification of the intermediate 121 with an alkyl ju-toluenesulfonate, giving the new ether 122. Still another example is the cleavage of the methyl ether of the prodigiosene 123 followed by re-etherification of the hydroxy compound 124, giving the prodigiosene 125.

Another method useful for preparing prodigiosenes having a B-ring ether other than methoxyl begins with cleavage of the methoxyl group of the intermediate 99. The resulting - hydroxy compound 126 is re-etherified using an alkyl tosylate reagent described above, giving 127. The more nucleophilic A-ring nitrogen of Compound 127 is alkylated, for example, with methyl iodide in the presence of a base, producing 128. The compound 127 can also be converted by the previously described series of reactions via 129 and 130 to the aldehyde 131. Aldehyde 131 can be used in coupling reactions with pynoles generating prodigiosene compounds in same way that the coupling of 1 with pynoles gives compounds of this class.

The preparations of Pynole-Type compounds I - V where R₂ is a trialkyl silyl ether, a tetrahydropyranyl ether, a methoxymethyl ether, a trichloroethyl carbonate, or an acyl group are carried out by methods known to the art (Greene and Wuts) and applied either to the prodigiosene alcohols such as 117 or dipynoles such as 126. As shown in Scheme I, the dipynole alcohol 126 reacts with a chlorotrialkylsilane 132 (for example, chlorotrimethylsilane or chloro-t-butyldimethylsilane), giving the trialkylsilylether 133. Using the previously described series of reactions for conversion of a methoxycarbonyl group to an aldehyde group, 133 is converted to the aldehyde 136 via the hydrazide 134 and the tosylhydrazide 135. The reaction of 136 with a pynole, such as for example 2, gives the prodigiosene 137. The trialkylsilyl ether is cleaved under the acidic conditions of the reaction. Reaction of 137 under conditions used in formation of 133 from 126 gives a trialkylsilyl ether of 137.

Methods for the preparation of the two enantiomers of cyclobutylprodigiosin are outlined in Scheme J. Scheme J.

-BINAP)₂(NEt₃)

SS-13 SR-13

Bu₃SnH Bu₃SnH AIBN AIBN

S-14 R-14

(S) -"Butylcycloheptylprodigiosin" (R) -"Butylcycloheptylprodigiosin" The catalyst used for the asymmetric reduction of ketone 11 (R,₄ is n-propyl, m is 1) is described in "Catalytic Asymmetric Synthesis," I. Ojima, ed.NCH, Ν.Y., 1993; see chapter 1 by H. Takaya, T. Ohta, and R. Noyori. The diastereomeric pair SS-12 and SR-12, or SS-13 and SR-13, are easily separable using common chromatographic or recrystallization methods. These methods can also be used to obtain enantiomers of a compound of Formula (I) where R₃ is other than n-butyl.

4.8. THERAPEUTIC/PROPHYLACTIC

10

ADMINISTRATION AND COMPOSITIONS

As used herein, the novel compounds of the present invention, the compounds of the present compositions, and the compounds of the present methods are known collectively as "Pynole-Type compounds".

- - Due to the activity of the Pynole-Type compounds, the Pynole-Type compounds are advantageously useful in veterinary and human medicine. For example, the Pynole-Type compounds are useful for the treatment or prevention of cancer or neoplastic disease or inhibiting the growth of a cancer cell or neoplastic cell. The Pynole-Type compounds are also useful for the treatment or prevention of a viral infection or inhibiting the replication or

~_π infectivity of a virus.

When administered to a subject, e.g., an animal for veterinary use or to a human for clinical use, or when made to contact a cell or tissue, the Pynole-Type compounds are preferably in isolated form. By "isolated" it is meant that prior to administration or contacting, a Pynole-Type compound is separated from other components of a synthetic

„ _r organic chemical reaction mixture or natural product source, e.g. , plant matter, tissue culture, bacterial broth, etc. Preferably, the Pynole-Type compounds are isolated via conventional techniques, e.g., extraction followed by chromotography, recrystalization, or another conventional technique. When in isolated form, the Pynole-Type compounds are at least 90%, preferably at least 95%, of a single Pynole-Type compound by weight of that

-,„ which is isolated. "Single Pynole-Type compound" means an enantiomer or a racemate of a Pynole-Type compound.

The invention provides methods of treatment and prophylaxis by administration to a subject of an effective amount of a Pynole-Type compound. The subject is preferably an animal, including, but not limited, to an animal such a cow, horse, sheep, pig, chicken,

- - turkey, quail, cat, dog, mouse, rat, rabbit, guinea pig, etc., and is more preferably a mammal, and most preferably a human. The present compositions, which comprise one or more Pynole-Type compounds, may be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.) and may be administered together with another biologically active agent. Administration can be systemic or local. Various delivery systems are known, e.g., encapsulation in liposomes, microparticles, microcapsules, capsules, etc., and can be used to administer a Pynole-Type compound of the invention. In certain embodiments, more than one Pynole-Type compound of the invention is administered to a subject. Methods of

₁ „ administration include but are not limited to intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, oral, sublingual, intranasal, intracerebral, intravaginal, transdermal, rectally, by inhalation, or topically to the ears, nose, eyes, or skin. The prefened mode of administration is left to the discretion of the practitioner, and will depend in-part upon the site of the medical condition (such as the site of cancer or viral

- ,. infection).

In specific embodiments, it may be desirable to administer one or more Pynole-Type compounds of the invention locally to the area in need of treatment. This may be achieved, for example, and not by way of limitation, by local infusion during surgery, topical application, e.g., in conjunction with a wound dressing after surgery, by injection, by means _ of a catheter, by means of a suppository, or by means of an implant, said implant being of a porous, non-porous, or gelatinous material, including membranes, such as sialastic membranes, or fibers. In one embodiment, administration can be by direct injection at the site (or former site) of a cancer, tumor or neoplastic or pre-neoplastic tissue. In another embodiment, administration can be by direct injection at the site (or former site) of a viral

₉^ infection.

In certain embodiments, it may be desirable to introduce one or more Pynole-Type compounds of the invention into the central nervous system by any suitable route, including intraventricular and intrathecal injection. Intraventricular injection may be facilitated by an intraventricular catheter, for example, attached to a reservoir, such as an Ommaya reservoir.

--_n Pulmonary administration can also be employed, e.g. , by use of an inhaler or nebulizer, and formulation with an aerosolizing agent, or via perfusion in a fluorocarbon or synthetic pulmonary surfactant. In certain embodiments, the Pynole-Type compounds can be formulated as a suppository, with traditional binders and carriers such as triglycerides. In another embodiment, the Pynole-Type compounds of the invention can be

__<_ delivered in a vesicle, in particular a liposome (see Langer, Science 249:1527-1533 (1990); Treat et al., in Liposomes in the Therapy of Infectious Disease and Cancer, Lopez-Berestein O 01/55131

and Fidler (eds.), Liss, New York, pp. 353-365 (1989); Lopez-Berestein, ibid., pp. 317-327 ; see generally ibid.) yet another embodiment, the Pynole-Type compounds can be delivered in a

_ controlled release system. La one embodiment, a pump may be used {see Langer, supra; Sefron, CRC Crit. Ref. Biomed. Eng. 14:201 (1987); Buchwald et al., Surgery 88:507 (1980); Saudek et al., N. Engl. J. Med. 321:574 (1989)). In another embodiment, polymeric materials can be used (see Medical Applications of Controlled Release, Langer and Wise (eds.), CRC Pres., Boca Raton, Florida (1974); Controlled Drug Bioavailability, Drug

_{1 ft} Product Design and Performance, Smolen and Ball (eds.), Wiley, New York (1984); Ranger and Peppas, J. Macromol. Sci. Rev. Macromol. Chem. 23:61 (1983); see also Levy et al., Science 228:190 (1985); During et al., Ann. Neural. 25:351 (1989); Howard et al., J. Neurosurg. 71:105 (1989)). In yet another embodiment, a controlled-release system can be placed in proximity of the target of the Pynole-Type compounds, e.g., the brain, thus

- . requiring only a fraction of the systemic dose (.see, e.g., Goodson, in Medical Applications of Controlled Release, supra, vol. 2, pp. 115-138 (1984)). Other controlled-release systems discussed in the review by Langer (Science 249:1527-1533 (1990)) maybe used.

The present compositions will contain a therapeutically effective amount of a Pynole-Type compound, preferably in purified form, together with a suitable amount of a

_?π pharmaceutically acceptable carrier so as to provide the form for proper administration to the patient.

In a specific embodiment, the term "pharmaceutically acceptable" means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized phaπnacopeia for use in animals, and more _<_ particularly in humans. The term "carrier" refers to a diluent, adjuvant, excipient, or vehicle with which a Pynole-Type compound is administered. Such pharmaceutical carriers can be liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. The pharmaceutical carriers can be saline, gum acacia, gelatin, starch paste, talc, keratin,

., colloidal silica, urea, and the like. In addition, auxiliary, stabilizing, thickening, lubricating and coloring agents may be used. When administered to a subject, the Pynole-Type compounds and pharmaceutically acceptable carriers are preferably sterile. Water is a prefened carrier when the Pynole-Type compound is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid

~ - carriers, particularly for injectable solutions. Suitable pharmaceutical carriers also include excipients such as starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. The present compositions, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering

- agents.

The present compositions can take the form of solutions, suspensions, emulsion, tablets, pills, pellets, capsules, capsules containing liquids, powders, sustained-release formulations, suppositories, emulsions, aerosols, sprays, suspensions, or any other form suitable for use. In one embodiment, the pharmaceutically acceptable carrier is a capsule . _n (see e.g., U.S. Patent No. 5,698,155). Other examples of suitable pharmaceutical carriers are described in "Remington's Pharmaceutical Sciences" by E.W. Martin.

The phrase "pharmaceutically acceptable salt(s)," as used herein includes but are not limited to salts of acidic or basic groups that may be present in compounds used in the present compositions. Compounds included in the present compositions that are basic in

- _<. nature are capable of forming a wide variety of salts with various inorganic and organic acids. The acids that may be used to prepare pharmaceutically acceptable acid addition salts of such basic compounds are those that form non-toxic acid addition salts, e., salts containing pharmacologically acceptable anions, including but not limited to sulfuric, citric, maleic, acetic, oxalic, hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, _n phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, acid citrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate (i.e., 1 , 1 -methylene-bis-(2-hydroxy-3-naphthoate)) salts. Compounds included in the present _<. compositions that include an amino moiety may form pharmaceutically or cosmetically acceptable salts with various amino acids, in addition to the acids mentioned above. Compounds, included in the present compositions, that are acidic in nature are capable of forming base salts with various pharmacologically or cosmetically acceptable cations. Examples of such salts include alkali metal or alkaline earth metal salts and, particularly,

-j„ calcium, magnesium, sodium lithium, zinc, potassium, and iron salts.

In a prefened embodiment, the Pynole-Type compounds are formulated in accordance with routine procedures as a pharmaceutical composition adapted for intravenous administration to human beings. Typically, Pynole-Type compounds for intravenous administration are solutions in sterile isotonic aqueous buffer. Where

„ necessary, the compositions may also include a solubilizing agent. Compositions for intravenous administration may optionally include a local anesthetic such as lignocaine to ease pain at the site of the injection. Generally, the ingredients are supplied either separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampoule or sachette indicating the quantity of active agent. Where the Pynole-Type compound is to be administered by infusion, it can be dispensed, for example, with an infusion bottle containing sterile pharmaceutical grade water or saline. Where the Pynole-Type compound is administered by injection, an ampoule of sterile water for injection or saline can be provided so that the ingredients may be mixed prior to administration.

_ „ Compositions for oral delivery may be in the form of tablets, lozenges, aqueous or oily suspensions, granules, powders, emulsions, capsules, syrups, or elixirs, for example. Orally administered compositions may contain one or more optionally agents, for example, sweetening agents such as fructose, aspartame or saccharin; flavoring agents such as peppermint, oil of wintergreen, or cherry; coloring agents; and preserving agents, to provide

- . a pharmaceutically palatable preparation. Moreover, where in tablet or pill form, the compositions may be coated to delay disintegration and absorption in the gastrointestinal tract thereby providing a sustained action over an extended period of time. Selectively permeable membranes sunounding an osmotically active driving compound are also suitable for orally administered Pynole-Type compounds. In these later platforms, fluid

-„ from the environment sunounding the capsule is imbibed by the driving compound, which swells to displace the agent or agent composition through an aperture. These delivery platforms can provide an essentially zero order delivery profile as opposed to the spiked profiles of immediate release formulations. A time delay material such as glycerol monostearate or glycerol stearate may also be used. Oral compositions can include standard

_{? <}- carriers such as mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc. Such carriers are preferably of pharmaceutical grade.

The amount of the Pynole-Type compound that will be effective in the treatment of a particular disorder or condition will depend on the nature of the disorder or condition, and can be determined by standard clinical techniques. In addition, in vitro or in vivo assays

_„ may optionally be employed to help identify optimal dosage ranges. The precise dose to be employed in the compositions will also depend on the route of administration, and the seriousness of the disease or disorder, and should be decided according to the judgment of the practitioner and each patient's circumstances. However, suitable dosage ranges for intravenous administration are generally about 20-500 micrograms of Pynole-Type

-j. compound per kilogram body weight. In specific prefened embodiments of the invention, the i.v. dose is 10-40, 30-60, 60-100, or 100-200 micrograms per kilogram body weight. In other embodiments, the i.v. dose is 75-150, 150-250, 250-375 or 375-500 micrograms per kilogram body weight. Suitable dosage ranges for intranasal administration are generally about 0.01 pg/kg body weight to 1 mg/kg body weight. Suppositories generally contain

_<. active ingredient in the range of 0.5% to 10% by weight. Oral compositions preferably contain 10% to 95% active ingredient, hi specific prefened embodiments of the invention, suitable dose ranges for oral administration are generally 1-500 micrograms of active compound per kilogram body weight. In specific prefened embodiments, the oral dose is 1-10, 10-30, 30-90, or 90-150 micrograms per kilogram body weight. In other _n embodiments, the oral dose is 150-250, 250-325, 325-450 or 450-1000 micrograms per kilogram body weight. Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems. Such animal models and systems are well known in the art.

The invention also provides pharmaceutical packs or kits comprising one or more

, _ containers filled with one or more Pynole-Type compounds of the invention. Optionally associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration. In certain prefened embodiment, e.g., when administered for the treatment _n or prevention of cancer, the kit may also contain one or more chemotherapeutic agents useful for treating cancer or a neoplastic disease to be administered in combination with a Pynole-Type compound of the invention. In certain prefened embodiments, e.g., when administered for the treatment or prevention of viral disease, the kit may contain one or more Pynole-Type comρound(s) of the invention and one or more anti- viral agents. ,.. The Pynole-Type compounds of the invention are preferably assayed in vitro, and then in vivo, for the desired therapeutic or prophylactic activity, prior to use in humans. For example, in vitro assays can be used to determine whether administration of a specific Pynole-Type compound or combination of Pynole-Type compounds is prefened.

In one embodiment, a patient tissue sample is grown in culture, and contacted or

-. „ otherwise administered with a Pynole-Type compound, and the effect of such Pynole-Type compound upon the tissue sample is observed and compared to a non-contacted tissue. In other embodiments, a cell culture model is used in which the cells of the cell culture are contacted or otherwise administered with a Pynole-Type compound, and the effect of such Pynole-Type compound upon the tissue sample is observed and compared to a non-

_ . contacted cell culture. Generally, a lower level of proliferation or survival of the contacted cells compared to the non-contracted cells indicates that the Pynole-Type compound is effective to treat a the patient. Such Pynole-Type compounds may also be demonstrated effective and safe using animal model systems.

. Other methods will be known to the skilled artisan and are within the scope of the invention.

4.9. INHIBITION OF CANCER AND NEOPLASTIC CELLS AND DISEASE

The Pynole-Type compounds may be demonstrated to inhibit tumor cell proliferation, cell transformation and tumorigenesis in vitro and in vivo using a variety of

10 assays known in the art, or described herein. Such assays may use cells of a cancer cell line, or cells from a patient. Many assays well-known in the art can be used to assess such survival and/or growth; for example, cell proliferation can be assayed by measuring (³H)-thymidine incorporation, by direct cell count, by detecting changes in transcription, translation or activity of known genes such as proto-oncogenes (e.g.,fos, myc) or cell cycle

15 markers (Rb, cdc2, cyclin A, Dl, D2, D3, E, etc). The levels of such protein and mRNA and activity can be determined by any method well known in the art. For example, protein can be quantitated by known immunodiagnostic methods such as Western blotting or immunoprecipitation using commercially available antibodies (for example, many cell cycle marker antibodies are from Santa Cruz Inc.). mRNA can be quantitated by methods that are

20 well known and routine in the art, for example by northern analysis, RNase protection, the polymerase chain reaction in connection with the reverse transcription, etc. Cell viability can be assessed by using trypan-blue staining or other cell death or viability markers known in the art. Differentiation can be assessed visually based on changes in moφhology, etc.

The present invention provides for cell cycle and cell proliferation analysis by a

25 variety of techniques known in the art, including but not limited to the following:

As one example, bromodeoxyuridine (BRDU) incoφoration may be used as an assay to identify proliferating cells. The BRDU assay identifies a cell population undergoing DNA synthesis by incoφoration of BRDU into newly synthesized DNA. Newly synthesized DNA may then be detected using an anti-BRDU antibody (see Hoshino et al.,

30 1986, Int. J. Cancer 38, 369; Campana et al, 1988, J. Immunol. Meth. 107, 79).

Cell proliferation may also be examined using (³H)-thymidine incoφoration (see e.g., Chen, J., 1996, Oncogene 13:1395-403; Jeoung, J., 1995, J. Biol. Chem. 270:18367-73). This assay allows for quantitative characterization of S-phase DNA synthesis. In this assay, cells synthesizing DNA will incoφorate (³H)-thymidine into newly

35 synthesized DNA. Incoφoration may then be measured by standard techniques in the art such as by counting of radioisotope in a Scintillation counter (e.g. Beckman LS 3800 Liquid Scintillation Counter).

Detection of proliferating cell nuclear antigen (PCNA) may also be used to measure ' cell proliferation. PCNA is a 36 kilodalton protein whose expression is elevated in proliferating cells, particularly in early GI and S phases of the cell cycle and therefore may serve as a marker for proliferating cells. Positive cells are identified by immunostaining using an anti-PCNA antibody (see Li et al, 1996, Cun. Biol. 6:189-199; Vassilev et al., 1995, J. Cell Sci. 108:1205-15).

₁ Cell proliferation may be measured by counting samples of a cell population over time (e.g. daily cell counts). Cells may be counted using a hemacytometer and light microscopy (e.g. HyLite hemacytometer, Hausser Scientific). Cell number may be plotted against time in order to obtain a growth curve for the population of interest. In a prefened embodiment, cells counted by this method are first mixed with the dye Trypan-blue

. _ (Sigma), such that living cells exclude the dye, and are counted as viable members of the population.

DNA content and/or mitotic index of the cells may be measured, for example, based on the DNA ploidy value of the cell. For example, cells in the GI phase of the cell cycle generally contain a 2N DNA ploidy value. Cells in which DNA has been replicated but

_9n have not progressed through mitosis (e.g. cells in S-phase) will exhibit a ploidy value higher than 2N and up to 4N DNA content. Ploidy value and cell-cycle kinetics may be further measured using propidum iodide assay (see e.g. Turner, T., et al., 1998, Prostate 34: 175-81). Alternatively, the DNA ploidy may be determined by quantitation of DNA Feulgen staining (which binds to DNA in a stoichiometric manner) on a computerized

_ , microdensitometrystaining system (see e.g., Bacus, S., 1989, Am. J. Pathol.135:783-92). In an another embodiment, DNA content may be analyzed by preparation of a chromosomal spread (Zabalou, S., 1994, Hereditas.120: 127-40; Pardue, 1994, Meth. Cell Biol. 44:333- 351).

The expression of cell-cycle proteins (e.g., CycA. CycB, CycE, CycD, cdc2, Cdk4/6,

_„ Rb, p21, p27, etc.) provide crucial information relating to the proliferative state of a cell or population of cells. For example, identification in an anti-proliferation signaling pathway may be indicated by the induction of p21^c,pl. Increased levels of p21 expression in cells results in delayed entry into GI of the cell cycle (Haφer et al., 1993, Cell 75:805-816; Li et al, 1996, Cun. Biol. 6:189-199). p21 induction may be identified by immunostaining using

_,. a specific anti-p21 antibody available commercially (e.g. Santa Cruz). Similarly, cell-cycle proteins may be examined by Western blot analysis using commercially available antibodies. In another embodiment, cell populations are synchronized prior to detection of a cell cycle protein. Cell cycle proteins may also be detected by FACS (fluorescence-activated cell sorter) analysis using antibodies against the protein of interest.

Detection of changes in length of the cell cycle or speed of cell cycle may also be used to measure inhibition of cell proliferation by the Pynole-Type compounds of the invention. In one embodiment the length of the cell cycle is determined by the doubling time of a population of cells (e.g., using cells contacted or not contacted with one or more Pynole-Type compounds of the invention). In another embodiment, FACS analysis is used

-. „ to analyze the phase of cell cycle progression, or purify GI , S, and G2/M fractions (see e.g., Delia, D. et al., 1997, Oncogene 14:2137-47).

Lapse of cell cycle checkpoint(s), and/or induction of cell cycle checkpoint(s), may be examined by the methods described herein, or by any method known in the art. Without limitation, a cell cycle checkpoint is a mechanism which ensures that a certain cellular

. _ events occur in a particular order. Checkpoint genes are defined by mutations that allow late events to occur without prior completion of an early event (Weinert, T., and Hartwell, L., 1993, Genetics, 134:63-80). Induction or inhibition of cell cycle checkpoint genes may be assayed, for example, by Western blot analysis, or by immunostaining, etc. Lapse of cell cycle checkpoints may be further assessed by the progression of a cell through the

_9n checkpoint without prior occunence of specific events (e.g. progression into mitosis without complete replication of the genomic DNA).

In addition to the effects of expression of a particular cell cycle protein, activity and post-translational modifications of proteins involved in the cell cycle can play an integral role in the regulation and proliferative state of a cell. The invention provides for assays

_ ,. involved detected post-translational modifications (e.g. phosphorylation) by any method known in the art. For example, antibodies that detect phosphorylated tyrosine residues are commercially available, and may be used in Western blot analysis to detect proteins with such modifications. In another example, modifications such as myristylation, may be detected on thin layer chromatography or reverse phase h.p.l.c. (see e.g., Glover, C, 1988,

_3Q Biochem. J. 250:485-91; Paige, L, 1988, Biochem J.;250:485-91).

Activity of signaling and cell cycle proteins and/or protein complexes is often mediated by a kinase activity. The present invention provides for analysis of kinase activity by assays such as the histone HI assay (see e.g., Delia, D. et al., 1997, Oncogene 14:2137-47).

.,_- The Pynole-Type compounds can also be demonstrated to alter cell proliferation in cultured cells in vitro using methods which are well known in the art. Specific examples of cell culture models include, but are not limited to, for lung cancer, primary rat lung tumor' cells (Swafford et al., 1997, Mol. Cell. Biol., 17:1366-1374) and large-cell undifferentiated cancer cell lines (Mabry et al, 1991, Cancer Cells, 3:53-58); colorectal cell lines for colon

. cancer (Park and Gazdar, 1996, J. Cell Biochem. Suppl. 24:131-141); multiple established cell lines for breast cancer (Hambly et al, 1997, Breast Cancer Res. Treat. 43:247-258; Gierthy et al, 1997, Chemosphere 34:1495-1505; Prasad and Church, 1997, Biochem. Biophys. Res. Commun. 232:14-19); a number of well-characterized cell models for prostate cancer (Webber et al., 1996, Prostate, Part 1, 29:386-394; Part 2, 30:58-64; and Part 3, 30:136-142; Boulikas, 1997, Anticancer Res. 17:1471-1505); for genitourinary cancers, continuous human bladder cancer cell lines (Ribeiro et al, 1997, Int. J. Radiat. Biol. 72:11-20); organ cultures of transitional cell carcinomas (Booth et al, 1997, Lab Invest. 76:843-857) and rat progression models (Vet et al., 1997, Biochim. Biophys Acta 1360:39-44); and established cell lines for leukemias and lymphomas (Drexler, 1994, Leuk.

₁₅ Res. 18:919-927, Tohyama, 1997, Int. J. Hematol. 65:309-317).

The Pynole-Type compounds can also be demonstrated to inhibit cell transformation (or progression to malignant phenotype) in vitro. In this embodiment, cells with a transformed cell phenotype are contacted with one or more Pynole-Type compounds, and examined for change in characteristics associated with a transformed phenotype (a set of in vitro characteristics associated with a tumorigenic ability in vivo), for example, but not 0 limited to, colony formation in soft agar, a more rounded cell moφhology, looser substratum attachment, loss of contact inhibition, loss of anchorage dependence, release of proteases such as plasminogen activator, increased sugar transport, decreased serum requirement, or expression of fetal antigens, etc. (see Luria et al., 1978, General Virology, 3d Ed., John Wiley & Sons, New York, pp. 436-446).

Loss of invasiveness or decreased adhesion may also be used to demonstrate the anti-cancer effects of the Pynole-Type compounds. For example, a critical aspect of the formation of a metastatic cancer is the ability of a precancerous or cancerous cell to detach from primary site of disease and establish a novel colony of growth at a secondary site. The

_ „ ability of a cell to invade peripheral sites is reflective of a potential for a cancerous state. Loss of invasiveness may be measured by a variety of techniques known in the art including, for example, induction of E-cadherin-mediated cell-cell adhesion. Such E-cadherin-mediated adhesion can result in phenotypic reversion and loss of invasiveness (Hordijk et al, 1997, Science 278:1464-66).

_ ₅ Loss of invasiveness may further be examined by inhibition of cell migration. A variety of 2-dimensional and 3 -dimensional cellular matrices are commercially available (Calbiochem-Novabiochem Coφ. San Diego, CA). Cell migration across or into a matrix may be examined by microscopy, time-lapsed photography or videography, or by any method in the art allowing measurement of cellular migration. In a related embodiment,

_<- loss of invasiveness is examined by response to hepatocyte growth factor (HGF). HGF- induced cell scattering is conelated with invasiveness of cells such as Madin-Darby canine kidney (MDCK) cells. This assay identifies a cell population that has lost cell scattering activity in response to HGF (Hordijk et al, 1997, Science 278:1464-66).

Alternatively, loss of invasiveness may be measured by cell migration through a

_ » chemotaxis chamber (Neuroprobe/ Precision Biochemicals Inc. Vancouver, BC). In such assay, a chemo-attractant agent is incubated on one side of the chamber (e.g., the bottom chamber) and cells are plated on a filter separating the opposite side (e.g., the top chamber). In order for cells to pass from the top chamber to the bottom chamber, the cells must actively migrate through small pores in the filter. Checkerboard analysis of the number of

- . cells that have migrated may then be conelated with invasiveness (see e.g., Ohnishi, T., 1993, Biochem. Biophys. Res. Commun.193:518-25).

The Pynole-Type compounds can also be demonstrated to inhibit tumor foπnation in vivo. A vast number of animal models of hypeφroliferative disorders, including tumorigenesis and metastatic spread, are known in the art (see Table 317-1, Chapter 317, _π "Principals of Neoplasia," in Harrison's Principals of Internal Medicine, 13th Edition, Isselbacher et al., eds., McGraw-Hill, New York, p. 1814, and Lovejoy et al., 1997, J. Pathol. 181:130-135). Specific examples include for lung cancer, transplantation of tumor nodules into rats (Wang et al., 1997, Ann. Thorac. Surg. 64:216-219) or establishment of lung cancer metastases in SCID mice depleted of NK cells (Yono and Sone, 1997, Gan To _ Kagaku Ryoho 24:489-494); for colon cancer, colon cancer transplantation of human colon cancer cells into nude mice (Gutman and Fidler, 1995, World J. Surg. 19:226-234), the cotton top tamarin model of human ulcerative colitis (Wanen, 1996, Aliment. Pharmacol. Ther. 10 Supp 12:45-47) and mouse models with mutations of the adenomatous polyposis tumor suppressor (Polakis, 1997, Biochim. Biophys. Acta 1332:F127-F147); for breast

_„ cancer, transgenic models of breast cancer (Dankort and Muller, 1996, Cancer Treat. Res. 83:71-88; Amundadittir et al., 1996, Breast Cancer Res. Treat. 39:119-135) and chemical induction of tumors in rats (Russo and Russo, 1996, Breast Cancer Res. Treat. 39:7-20); for prostate cancer, chemically-induced and transgenic rodent models, and human xenograft models (Royai et al., 1996, Semin. Oncol. 23:35-40); for genitourinary cancers, induced

_ .. bladder neoplasm in rats and mice (Oyasu, 1995, Food Chem. Toxicol 33:747-755) and xenografts of human transitional cell carcinomas into nude rats (Janett et al., 1995, J. Endourol. 9:1-7); and for hematopoietic cancers, transplanted allogeneic manow in animals (Appelbaum, 1997, Leukemia 11 (Suppl. 4):S15-S17). Further, general animal models applicable to many types of cancer have been described, including, but not restricted to, the

_<. p53-deficient mouse model (Donehower, 1996, Semin. Cancer Biol. 7:269-278), the Min mouse (Shoemaker et al., 1997, Biochem. Biophys. Acta, 1332:F25-F48), and immune responses to tumors in rat (Frey, 1997, Methods, 12:173-188).

For example, a Pynole-Type compound can be administered to a test animal, preferably a test animal predisposed to develop a type of tumor, and the test animal

- „ subsequently examined for an decreased incidence of tumor formation in comparison with controls not administered the Pynole-Type compound. Alternatively, a Pynole-Type compound can be administered to test animals having tumors (e.g., animals in which tumors have been induced by introduction of malignant, neoplastic, or transformed cells, or by administration of a carcinogen) and subsequently examining the tumors in the test animals

. _ for tumor regression in comparison to controls not administered the Pynole-Type compound.

4.9.1. TREATMENT OR PREVENTION OF CANCER OR A NEONATAL DISEASE IN COMBINATION WITH CHEMOTHERAPY OR RADIOTHERAPY

20 Cancer or a neoplastic disease, including, but not limited to, neoplasms, tumors, metastases, or any disease or disorder characterized by uncontrolled cell growth, can be treated or prevented by administration of a composition comprising a pharmaceutically acceptable carrier and a Pynole-Type compound or a pharmaceutically acceptable salt thereof. The compositions can comprise one or more Pynole-Type compounds, or a

25 pharmaceutically acceptable salt thereof. hi certain embodiments, one or more Pynole-Type compounds of the invention are used to treat or prevent cancer or neoplastic disease in combination with one or more anti- cancer, chemotherapeutic agents including, but not limited to, methotrexate, taxol, mercaptopurine, thioguanine, hydroxyurea, cytarabine, cyclophosphamide, ifosfamide,

30 nitrosoureas, cisplatin, carboplatin, mitomycin, dacarbazine, procarbizine, etoposides, campathecins, bleomycin, doxorubicin, idarubicin, daunorubicin, dactinomycin, plicamycin, mitoxantrone, asparaginase, vinblastine, vincristine, vinorelbine, paclitaxel, and docetaxel. In a prefened embodiment, one or more Pynole-Type compound of the invention is used to treat or prevent cancer or neoplastic disease in combination with one or more

35 chemotherapeutic or other anti-cancer agents including, but not limited to those presented in Table 7.

TABLE 7 CHEMOTHERAPEUTICS AND OTHER ANTI-CANCER AGENTS

Radiation: γ-radiation

Alkylating agents Nitrogen mustards: cyclophosphamide

Ifosfamide trofosfamide

Chlorambucil

Nitro soureas: carmustine (BCNU)

Lomustine (CCNU)

Alkylsulphonates busulfan

Treosulfan

Triazenes: Dacarbazine

Platinum containing compounds: Cisplatin carboplatin

Plant Alkaloids Vinca alkaloids: vincristine

Vinblastine

Vindesine

Vinorelbine

Taxoids: paclitaxel

Docetaxol

DNA Topoisomerase Inhibitors Epipodophyllins: etoposide Teniposide Topotecan

9-aminocamptothecin campto irinotecan crisnatol mytomycins: mytomycin C Mytomycin C Anti-metabolites Anti-folates: DHFR inhibitors: methotrexate

Trimetrexate

IMP dehydrogenase Inhibitors: mycophenolic acid

Tiazofurin

10

Ribavirin

EICAR

Ribonuclotide reductase Inhibitors: hydroxyurea deferoxamine

15

Pyrimidine analogs: Uracil analogs 5-Fluorouracil

Floxuridine

Doxifluridine

Ratitrexed

20

Cytosine analogs cytarabine (ara C)

Cytosine arabinoside fludarabine

_ Purine analo s: mercaptopurine Thioguanine

Hormonal therapies: Receptor antagonists: _„ Anti-estrogens Tamoxifen

Raloxifene megestrol

LHRH agonists: goscrclin

Leuprolide acetate _. _ Anti-androgens : flutamide bicalutamide Retinoids/Deltoids Vitamin D3 analogs: EB 1089 CB 1093 KH 1060

Photodvamic therapies: vertoporfin (BPD-MA) Phthalocyanine photosensitizer Pc4 Demethoxy-hypocrellin A (2BA-2-DMHA)

Cytokines: friterferon-α friterferon-γ Tumor necrosis factor

Others:

Isoprenylation inhibitors: Lovastatin Dopaminergic neurotoxins: l-methyl-4-phenylpyridinium ion Cell cycle inhibitors: staurosporine

Actinomycins: Actinomycin D Dactinomycin

Bleomycins: bleomycin A2 Bleomycin B2 Peplomycin

Anthracyclines: daunorubicin

Doxorubicin (adriamycin)

Idarubicin

Epirubicin

Pirarubicin

Zorubicin

Mitoxantrone

MDR inhibitors: verapamil Ca²⁺ATPase inhibitors: thapsigargin

In other embodiments, a composition comprising one or more Pynole-Type compounds is administered along with radiation therapy and/or with one or a combination of chemotherapeutic agents, preferably with one or more chemotherapeutic agents with which treatment of the cancer has not been found to be refractory. The Pynole-Type compound can be administered to a patient that has also undergone surgery as treatment for the cancer.

₁ „ In another specific embodiment, the invention provides a method to treat or prevent cancer that has shown to be refractory to treatment with a chemotherapy and/or radiation therapy.

In a specific embodiment, a composition comprising one or more Pynole-Type compounds is administered concunently with chemotherapy or radiation therapy. In

. _ another specific embodiment, chemotherapy or radiation therapy is administered prior or subsequent to administration of a present composition, preferably at least an hour, five hours, 12 hours, a day, a week, a month, more preferably several months (e.g., up to three months), subsequent to administration of a therapeutic of the invention.

The chemotherapy or radiation therapy administered concunently with, or prior or _ subsequent to, the administration of a present composition can be accomplished by any method known in the art. The chemotherapeutic agents are preferably administered in a series of sessions, any one or a combination of the chemotherapeutic agents listed above can be administered. With respect to radiation therapy, any radiation therapy protocol can be used depending upon the type of cancer to be treated. For example, but not by way of

₉. limitation, x-ray radiation can be administered; in particular, high-energy megavoltage (radiation of greater that 1 MeV energy) can be used for deep tumors, and electron beam and orthovoltage x-ray radiation can be used for skin cancers. Gamma-ray emitting radioisotopes, such as radioactive isotopes of radium, cobalt and other elements, may also be administered to expose tissues to radiation. . _Λ Additionally, the invention provides methods of treatment of cancer or neoplastic disease with a present composition as an alternative to chemotherapy or radiation therapy where the chemotherapy or the radiation therapy has proven or may prove too toxic, e.g., results in unacceptable or unbearable side effects, for the subject being treated. The subject being treated with the present compositions may, optionally, be treated with other cancer

₃₅ treatments such as surgery, radiation therapy or chemotherapy, depending on which treatment is found to be acceptable or bearable. 4.9.2. CANCER AND NEOPLASTIC DISEASE TREATABLE OR PREVENTABLE

Cancers or neoplastic diseases and related disorders that can be treated or prevented by administration of the present compositions include but are not limited to those listed in

Table 8 (for a review of such disorders, see Fishman et al., 1985, Medicine, 2d Ed., J.B.

Lippincott Co., Philadelphia):

TABLE 8

10 CANCERS AND NEOPLASTIC DISORDERS

Leukemia acute leukemia acute lymphocytic leukemia acute myelocytic leukemia 15 myeloblastic promyelocytic myelomonocytic monocytic erythroleukemia chronic leukemia chronic myelocytic (granulocytic) leukemia „ chronic lymphocytic leukemia

Polycythemia vera Lymphoma

Hodgkin's disease non-Hodgkin's disease Multiple myeloma Waldenstrom's macroglobulinemia Heavy chain disease 25 Solid tumors sarcomas and carcinomas fibrosarcoma myxosarcoma liposarcoma chondrosarcoma osteogenic sarcoma ~„ chordoma angiosarcoma endotheliosarcoma lymphangiosarcoma lymphangioendothehosarcoma synovioma mesothelioma Ewing's tumor 35 leiomyosarcoma rhabdomyosarcoma colon carcinoma pancreatic cancer breast cancer ovarian cancer prostate cancer squamous cell carcinoma basal cell carcinoma adenocarcinoma sweat gland carcinoma sebaceous gland carcinoma papillary carcinoma papillary adenocarcinomas cystadenocarcinoma medullary carcinoma bronchogenic carcinoma renal cell carcinoma hepatoma bile duct carcinoma choriocarcinoma seminoma embryonal carcinoma

Wilms' tumor cervical cancer uterine cancer testicular tumor lung carcinoma small cell lung carcinoma bladder carcinoma epithelial carcinoma glioma astrocytoma medulloblastoma craniopharyngioma ependymoma pinealoma hemangioblastoma acoustic neuroma ^■ oligodendroglioma meningioma melanoma neuroblastoma retinoblastoma

In specific embodiments, cancer, malignancy or dysproliferative changes (such as metaplasias and dysplasias), or hypeφroliferative disorders, are treated or prevented in the ovary, breast, colon, lung, skin, pancreas, prostate, bladder, or uterus. In other specific embodiments, sarcoma, melanoma, or leukemia is treated or prevented. In a highly prefened embodiment, the present compositions are used to treat or prevent cancers including prostate (more preferably hormone-insensitive), Neuroblastoma, Lymphoma (preferably follicular or Diffuse Large B-cell), Breast (preferably Estrogen- receptor positive), Colorectal, Endometrial, Ovarian, Lymphoma (preferably non- Hodgkin's), Lung (preferably Small cell), or Testicular (preferably germ cell).

In a prefened embodiment, the present compositions are used to inhibit the growth of a cell derived from a cancer or neoplasm such as prostate (more preferably hormone- insensitive), Neuroblastoma, Lymphoma (preferably follicular or Diffuse Large B-cell), . „ Breast (preferably Estrogen-receptor positive), Colorectal, Endometrial, Ovarian, Lymphoma (preferably non-Hodgkin's), Lung (preferably Small cell), or Testicular (preferably germ cell).

In specific embodiments of the invention, the present compositions are used to inhibit the growth of a cell, said cell being derived from a cancer or neoplasm in Table 8 or - _. herein.

4.9.3. DEMONSTRATION OF INHIBITION OF VIRUSES AND VIRAL INFECTIONS _n The Pynole-Type compounds may be demonstrated to inhibit the replication or infectivity of a virus or a virus-infected cell in vitro or in vivo using a variety of assays known in the art, or described herein. In certain embodiments, such assays may use cells of a cell line, or cells from a patient. In specific embodiments, the cells may be infected with a virus prior to the assay, or during the assay. The cells may be contacted with a virus. In , certain other embodiments, the assays may employ cell-free viral cultures.

In one embodiment, a Pynole-Type compound is demonstrated to have activity in treating or preventing viral disease by contacting cultured cells that exhibit an indicator of a viral reaction (e.g., formation of inclusion bodies) in vitro with the Pynole-Type compoimd, and comparing the level of said indicator in the cells contacted with the Pynole-Type

-,„ compound with said level of said indicator in cells not so contacted, wherein a lower level in said contacted cells indicates that the Pynole-Type compound has activity in treating or preventing viral disease. Cell models that can be used for such assays include, but are not limited to, viral infection of T lymphocytes (Selin et al., 1996, J. Exp. Med. 183:2489- 2499); hepatitis B infection of dedifferentiated hepatoma cells (Raney et al., 1997, J. Virol.

_ 71 : 1058-1071); viral infection of cultured salivary gland epithelial cells (Clark et al., 1994, Autoimmunity 18:7-14); synchronous HIV-1 infection of CD4⁺ lymphocytic cell lines (Wainberg et al., 1997, Virology 233:364-373); viral infection of respiratory epithelial cells (Stark et al., 1996, Human Gene Ther. 7:1669-1681); and amphotrophic retroviral infection of NIH-3T3 cells (Morgan et al, 1995, J. Virol. 69:6994-7000). hi another embodiment, a Pynole-Type compound can be demonstrated to have activity in treating or preventing viral disease by administering said Pynole-Type compound to a test animal having symptoms of a viral infection, such as characteristic respiratory symptoms in animal models, or which test animal does not exhibit a viral reaction and is subsequently challenged with an agent that elicits an viral reaction, and measuring the

₁ „ change in the viral reaction after the administration of said Pynole-Type compound, wherein a reduction in said viral reaction or a prevention of said viral reaction indicates that the Pynole-Type compound has activity in treating or preventing viral disease. Animal models that can be used for such assays include, but are not limited to, guinea pigs for respiratory viral infections (Kudlacz and Knippenberg, 1995, Inflamm. Res. 44:105-110);

_ ^ mice for influenza virus infection (Dobbs et al., 1996, J. Immunol. 157:1870-1877); lambs for respiratory syncitial virus infection (Masot et al, 1996, Zentralbl. Veterinarmed. 43:233- 243); mice for neurotrophic virus infection (Barna et al., 1996, Virology 223:331-343); hamsters for measles infection (Fukuda et al, 1994, Acta Otolaryngol. Suppl (Stockh.) 514:111-116); mice for encephalomyocarditis infection (Hirasawa et al., 1997, J. Virol.

_9π 71:4024-4031); and mice for cytomegalovirus infection (Orange and Biron, 1996, J.

Immunol. 156:1138-1142). In certain embodiments of the invention more than one Pynole- Type compound is administered to a test animal, virus, or viral-infected cell.

4.9.4. VIRUSES AND VIRAL INFECTIONS _. Viruses and viral infections that can be treated or prevented by administration of a composition of the invention include but are not limited to those listed in Table 9 including, but not limited to, DNA viruses such as hepatitis type B and hepatitis type C virus; parvoviruses, such as adeno-associated virus and cytomegalovirus; papovaviruses such as papilloma virus, polyoma viruses, and SV40; adenoviruses; heφes viruses such as heφes

_„ simplex type I (HSV-I), heφes simplex type II (HSV-II), and Epstein-Ban vims; poxviruses, such as variola (smallpox) and vaccinia virus; and RNA viruses, such as human immunodeficiency virus type I (HIV-I), human immunodeficiency virus type II (HIN-H), human T-cell lymphotropic virus type I (HTLV-I), human T-cell lymphotropic virus type II (HTLV-II), influenza virus, measles virus, rabies virus, Sendai virus, picornaviruses such as

_ - poliomyelitis virus, coxsackieviruses, rhinoviruses, reoviruses, togaviruses such as rubella virus (German measles) and Semliki forest virus, arboviruses, and hepatitis type A virus. In a prefened embodiment of the invention, the compositions of the invention are used to treat or prevent a viral infection associated with a virus as listed in Table 9. In another prefened embodiment, the compositions of the invention are used inhibit the replication or infectivity of a virus listed in Table 9. In yet another prefened embodiment, one or more Pynole-Type compounds of the invention are used inhibit the growth of a cell infected with a virus listed in Table 9.

TABLE 9

Heφesviruses: EBN

HHN-8 (KSHV) Heφesvirus saimiri

Adenoviruses: All strains

Retro viruses: HIV- l and 2 HTLV-I

Human Papillomaviruses: HPV - all strains

Birnaviruses: Infectious pancreatic necrosis virus

Other: African Swine Fever virus (all strains)

5. EXAMPLES

The following examples are set forth to assist in understanding the invention and should not, of course, be construed as specifically limiting the invention described and claimed herein. Such variations of the invention, including the substitution of all equivalents now known or later developed, which would be within the purview of those skilled in the art, and changes in Formulation or minor changes in experimental design, are to be considered to fall within the scope of the invention incoφorated herein. Example 1

2-EthyI-ll-((3-methoxy-5-(lH-pyrroI-2-yl)-2H-pyrrol-2-ylidene)methyI)-10 -azabicyclo[7.2.1]dodeca-9(12),ll-diene

The pynole 2 (R₁₄ is Me, m is 1; 2-ethyl- 10-azabicyclo[7.2.1]doceca-9(l 2), 11-diene) (1.0 mmol) is added to a stined solution of 1 (4-methoxy-2, 2'-bipynole-5-carboxaldehyde) (Boger and Patel, 1988, J. Org. Chem. 53:1405) (1.0 mmol) in methanol (5 mL) under

- j. argon. The solution is warmed to near the boiling point of the solvent and while still warm, concentrated hydrochloric acid (10 drops) is added. The reaction mixture is left to stand at room temperature and progress of the reaction is monitored using thin-layer chromatography. When the reaction is complete, the solvent is removed under reduced pressure and the residue is purified using column chromatography (neutral alumina),

₉₀ providing the above-titled compound.

Example 2 2-Benzyl-ll-((3-methoxy-5-(lH-pyrroI-2-yI)-2H-pyrrol-2-yIidene)methyl)-10- azabicyc!o[7.2.1]dodeca-9(12),ll-diene

A solution of the pynole 2 (R₁₄ is Ph, m is 1; 2-benzyl-10-azabicyclo[7.2.1]doceca- 9( 12), 11-diene) (1.0 mmol) in π-pentane (4 mL) is added to a solution of 1 (1.0 mmol) in o pentane (5 mL) under argon. The resulting solution is stined and cooled in an ice-water bath. Phosphorous oxychloride (1.0 mmol) is added and the resulting mixture is stined until reaction is complete as determined by thin-layer chromatography. The resulting solid precipitate is collected by filtration, washed with cold pentane, and added to a suspension of excess moist calcium hydroxide in pentane (10 mL). The resulting mixture is mixed vigorously, and the pentane solution is separated, dried (Na^O^, filtered and concentrated, giving a crude mixture of the above-titled compound. The crude mixture is purified using chromatography over neutral alumina to obtain the above-titled compound.

Example 3 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pyrrol-2-yl)-2H-pyrrol-2-

10 yIidene)methyl)-l-ethyI-2H-isoindoIe

A solution of the pynole 40 (R₂ is Et, R₅ is H, n is 2; 2-ethyl-3,4- tetramethylenepynole) (1.0 mmol) in methanol (2 mL) is added to a stined solution of 1 (4- methoxy-2,2'-bipynole-5-carboxaldehyde) (1.0 mmol) in methanol (3 mL) under argon. ₀ The solution is warmed to near the boiling point of the solvent and, while still warm, concentrated hydrochloric acid (10 drops) is added. The reaction mixture is left to stand at room temperature and progress of the reaction is followed using thin-layer chromatography. When the reaction appears complete, the solvent is removed under reduced pressure and the residue is purified using chromatography (neutral alumina) giving the above-titled

₉.- compound.

Example 4 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pyrrol-2-yl)-2_JfiT-pyrrol-2- yIidene)methyl)-5-methyI-l_H^r-indole

32 Following the procedures described in Example 1, pynole 57 and 1 react, giving the above-titled compound. Example 5 Methoxy-5-((5-(2-(2-methyl)-furyI)-2H-pyrroI-2-yIidene)methyl)-2, 2'-bi-liϊ- pyrrole

10

Following the procedures described in Example 1, 2-(2-(2-methyl)-furyl)-lH-pynole (97) and 1 react, providing the above-titled compound.

Example 6 , ₅ Preparation of two diastereoisomers of l-(10-(toluenesulfonyl)-10- azabic clo [7.2.1 J dodec-1 (12)-en-2-yl)b utan- l-ol

A solution of 11 (R₁₄ is n-propyl, m is 1; A. Fϋrstner et al., J. Am. Chem. Soc. 120, ₂₅ 8305-8314, 1998) (2.0 mmol) in ethanol (20 mL) containing Ru₂Cl₄((S)-BINAP)₂-NEt₃ (0.1 mol) is hydrogenated under H₂ at 3 atmospheres of pressure. The resulting mixture is warmed until an equivalent of hydrogen is consumed. The reaction mixture is cooled to room temperature, the reaction vessel is flushed with nitrogen, and the solvent is removed under reduced pressure. The mixture of diastereoisomers of 12 (R₁ = Ch₃CH₂CH₂, m= 1) is 30 separated using conventional chromato graphic techniques.

35 Example 7 A diastereoisomer of thiocarbonic acid 0-phenyl ester 0-(l-(10- (toluenesuIfonyI)-10-azabicyclo[7.2.1]dodec-l(12)-en-2-yl)butyl) ester

Phenylchlorothiono formate (3.0 mmol) and pyridine (2.0 mmol) are added in methylene chloride (10 mL) to a solution of one of the diastereomers obtained from Example 6 (1 mmol). The solution is stined under argon at ice bath temperature. The solution is stined at room temperature for 30 hours, after which excess reagent is quenched

15 with methanol. The resulting solution is concentrated, and the residue is purified using high-performance liquid chromatography, affording the above-titled compound.

Example 8 ₉ „ Prep aration of an enantiomer of 2-butyl-l 0-(toluenesulfonyl)-l 0- azabicyc!o[7.2.1]dodec-l(12)-ene

AJDBN (0.20 mmol) and tri-«-butyltinhydride (2.0 mmol) are added to a solution of -_π the product of Example 7 (1 mmol) in toluene (10 mL). The mixture is stined at 75 °C until reaction is complete as detected by thin-layer chromatography. Solvent is removed under reduced pressure and the residue is purified using high-performance liquid chromatography, affording the above-titled compound.

35 Example 9 Preparation of an enantiomer of 2-butyI-l 0-azabicycIo [7.2.1 Jdodeca- l(ll),9(12)-diene

10

1,3-Diaminopropane (30 mL) is added to potassium hydride (10 mmol) under argon at room temperature. The mixture is stined 3 hours. The resulting mixture is added dropwise at -15 °C over a period of an hour to a solution of the product of Example 8

(1 mmol) in 1,3-diaminopropane (15 mL). The resulting mixture is stined at -15 °C for

. ^ three hours and then is poured carefully into cold water. The aqueous phase is extracted with EtOAc, and the organic extracts are dried (Na_jSO , filtered and concentrated, affording a crude mixture of the above-titled compound. The crude mixture is purified using conventional chromatographic methods.

„ Example 10

An enantiomer of 2-butyl-ll-((3-methoxy-5-(lH-pyrroI-2-yl)-2H-pyrrol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),ll-diene

-₀ Using the procedure described in Example 1, the product of Example 9 and 1 react, affording the above-titled compound.

35 Example 11 The enantiomer of 2-butyI-l l-((3-methoxy-5-(lH-pyrrol-2-yl)-2.fir-pyrrol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),ll-diene opposite from that of Example 10.

The diastereomer obtained from the procedure of Example 6 but not used in Example 7 is reacted according to Examples 7-10 to afford the above-titled compound.

Example 12

10 Butyl-metø-cycloheptylprodiginine via fermentation.

One Bennett's agar slant of Streptoverticillium baldacci (ATCC no. 25189) was inoculated into five 50 mL cultures of fermentation medium. The fermentation medium consisted of lOg soybean meal (Central Soya, Bellevue, OH), 20g glucose, lOg meat

. _ peptone 851C (Difco Laboratories, Detroit, MI) and 5g sodium chloride in 1 liter of tap water, pH adjusted to 7.5 (J. Heterocycl. Chem. 10:925-929, 1973). The cultures were incubated at 28°C for 4 days with -220 φm shaking. Twenty 500 mL cultures were then inoculated with 10 mL of the above culture and incubated at 28°C for 5 days with -220 φm shaking. _π The bacterial cells were harvested after 5 days by filtration, then mechanically homogenized in three, 1 -liter aliquots of ethyl acetate. All of the extracts were pooled and separated from cell debris before evaporation under vacuum to near complete dryness. While the extract was drying, a 1 liter Partition-chromatography solvent system consisting of hexane: ethyl acetate: methanol: water (1:3:3:3 ratio) was prepared in a separating funnel.

₉ The dried extract was dissolved in the upper solvent layer of the solvent system.

The bottom layer of the solvent system was then added, and the resulting mixture was shaken in a separating funnel. The bottom layer was then discarded, and the upper, dark-red colored layer was completely dried under a vacuum. The resulting residue was dissolved in approximately 50 mL of toluene.

- „ The toluene solution of the residue was applied to a 250g hexane-packed alumina column. Fresh alumina was used for every batch and care was taken to not let the column dry out. The column was washed with 1-2 volumes of hexane to remove any toluene or lipids from the extract. Fractions of 10-15 mL each were collected as the extract was slowly eluted with 4-5 column volumes of hexane:ethyl acetate (9:1 ratio). The eluate containing a

_ - main red zone was evaporated and dissolved in 10-20 mL of dichloromethane. The dissolved eluate was then applied to a hexane-packed 200g silica gel (60-200 mesh, Bayer, Pittsburgh, PA) column. The column was washed with 1-2 column volumes of hexane to remove any toluene or lipids from the extract. Fractions of 10-15 mL each were collected as the extract was slowly eluted with 4-5 column volumes of hexane: ethyl acetate (9:1 ratio). The eluate containing a red-pink color zone was then dried under a vacuum to

5 provide the above-titled compound, which was >99% pure as shown by NMR and MS.

Example 13 In Vitro Assay Demonstrating Anti-Oncogenic Effects Of Illustrative Pyrrole- - _n Type Compounds Butyl-wetα-Cy oheptylprodiginine and Ethyl-wetα- Cyclononylprodiginme.

TABLE 10

Compound Concentration Time of Cvtoxicitv (% Dead cells) μM Exposure

15 (h) .

Normal MCF-7 MBA-

Human Breast MB231

Breast Cancer Breast

Epithelial cells Cancer cells

Cells

Butyl- etα- 0 72 5 24 20

20 cycloheptylprodiginin 0.25 72 5 70 64 e 1.0 72 5 100 100

2.0 72 15 100 100

T hy -meta- 0 24 17 14 N.D. cyclononylprodiginine 0.2 24 10 45 N.D.

1.0 24 9 62 N.D.

25 2.0 24 15 65 N.D.

Methods

An in vitro cytotoxicity assay was used to demonstrate the selective toxicity of butyl-znetα-cycloheptylprodiginine and ethyl- etα-cyclononylprodiginine to oncogenic cells, relative to that of normal cells. Normal and cancerous human breast cells were plated 3° at a density of -70,000-80,000 cells/well in 24 well plates. Each test compound was added to the cell media at the indicated concentration and incubated at 37°C in a CO₂ incubator for the indicated time. Following incubation, cells were harvested and exposed to trypan blue dye; dead cells were stained exclusively (living cells remained unstained) and counted.

35 Results

The cytotoxicity assay showed that butyl-røetα-cycloheptylprodiginine selectively killed the breast cancer cells, relative to normal human breast epithelial cells. As seen in Table 10, a 0.25 μM concentration of butyl- etα-cycloheptylprodiginine causes only 5% cell death in normal cells as compared to 70% and 64% cell death in cancer cells. Ethyl- wetα-cyclononylprodiginine had similar effects. These results indicate that butyl- etα- cycloheptylprodiginine and ethyl-wetα-cyclononylprodiginine, illustrative Pynole-Type compounds of the present invention, are selective anti-cancer agents.

The present invention is not to be limited in scope by the specific embodiments disclosed in the examples which are intended as illustrations of a few aspects of the invention and any embodiments which are functionally equivalent are within the scope of this invention. Indeed, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art and are intended to fall within the appended claims.

A number of references have been cited, the entire disclosures of which are incoφorated herein by reference.

Claims

What is claimed is:

1. A compound having the general Formula (I):

I

or a pharmaceutically acceptable salt thereof, wherein: . . each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃,

-CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R„R_I2, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; _n R₃ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl,

-CH(R,₄)(R₁₅) wherein R₁₄ and R_I5 are independently C,-C₁₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups;

R,, and R,₂ are independently C,-C₃ straight or branched chain alkyl; R_I6 and R,₇ is -H; and -„ m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: butyl-meta-cycloheptylprodiginine, metacycloprodigiosin,

4-ethoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi-l H-pynole, ,_<_ or 4-propoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi-l H-pynole.

2. The compound of claim 1, wherein: each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; _r R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl,

R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Fonnula (I) is not: - _ butyl-meta-cycloheptylprodiginine, metacycloprodigiosin,

4-ethoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi-l H-pynole, or 4-propoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi-l H-pynole.

3. The compound of claim 1 , wherein: ^'

15 each R, is -H;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, n-C,-C,₀ alkyl and -CH₂C₆H₅; R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5;

20 with the proviso that the compound of Formula (I) is not: butyl-meta-cycloheptylprodiginine, metacycloprodigiosin,

4-ethoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2 -bi-l H-pynole, _{9 i-} or 4-propoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi-lH-pynole.

4. The compound of claim 1, wherein: each R, is independently selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅; -_n R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl,

-CH₂C₆H_S, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that when m is 3, R₃ is not -CH₂CH₃ and when m is 1, R₃ is not 35 "(CH₂)₃CH₃.

5. The compound of claim 1 , wherein: each R, is independently selected from the group consisting of -H and -CH₃;

R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, -CH₃, -n-C₃H₇, -z^'-C₃H₇, C₅-C₁₀ straight chain alkyl, (l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl;

R,₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5.

10

6. The compound of claim 1, wherein: each R, is independently selected from the group consisting of -H and -CH₃; R₂ is selected from the group consisting of -CH₃ and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, -CH₂C₆H₅, - _<. butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R₁₆ and R₁₇ are -H; and m is 2, 4 or 5.

7. The compound of claim 1, selected from the group consisting of :

_2Q 2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2. l]dodeca-9(12),l 1-diene; l l-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

2-Methyl-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- _. 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Proρyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-n-Pentyl-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 3₀ 2-Benzyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-n-Pentyl- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-n-Pentyl- 11 -((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ~ - ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 01/55131

(S)-2-»-Butyl- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9( 12), 11 -diene;

(R)-2-«-Butyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l 0-azabicyclo[7.2. l]dodeca-9(12), 11-diene;

(S)-2-Ethyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

(R)-2-Ethyl- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; _{j 0} (S)-2-Methyl- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo [7.2.1] dodeca-9( 12), 11 -diene;

(S)-2-rz-PropyI- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ₁.. ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-«-Propyl- 1 l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo [7.2.1 ] dodeca-9( 12), 11 -diene;

2-Methyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 1 l-azabicyclo[8.2. l]trideca-10(13),12-diene; ₂₀ 2-Ethyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-ll- azabicyclo[8.2.1]trideca-10(13),12-diene;

2-«-Propyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 1 l-azabicyclo[8.2. l]trideca-10(13),12-diene;

2-n-Butyl-12-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- ₂₅ 1 l-azabicyclo[8.2. l]trideca-10(13),12-diene;

2-«-Pentyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

12-((3-Methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)-l l- azabicyclo[8.2. l]trideca-10(13), 12-diene; ₃₀ 2-Methyl-13-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2. l]tetradeca-l 1 (14), 13-diene;

13-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2. l]tetradeca-l l(14),13-diene;

2-Ethyl-12-methyl-13-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- 3. 2-ylidene)methyl)- 12-azabicyclo[9.2.1 jtetradeca- 11 (14), 13-diene; 2-Ethyl-12-methyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 12-azabicyclo [9.2.1 jtetradeca- 11 ( 14), 13-diene;

2-«-Propyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l 1 (14), 13-diene;

2-τι-Butyl- 13-((3-methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

14-((3-Methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 13- azabicyclo[ 10.2.1 jpentadeca- 12( 15), 14-diene; ₁₀ 2-Butyl- 1 l-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(12), 11 -diene;

2-Butyl- 11 -((3-methoxy-5-(l -methyl- lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-methyl-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl- 11 -((3-methoxy-5 -( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- - _ methyl-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

2-Ethyl- 11 -((3-benzyloxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

2-Butyl- 11 -((3-hydroxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2. l]dodeca-9(12),l 1-diene; ₀ 2-Butyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; l l-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl- 11 -((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- _9ς 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-/z-Propyl- 11 -((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-n-Pentyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2. l]dodeca-9(12), 11-diene; ₀ 2-Benzyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl- 14-((3-methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 13-azabicyclo[10.2.1]pentadeca-12(15),14-diene;

15-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-14- ₃₅ azabicyclo[11.2.1]pentadeca-13(16),15-diene; 2-Methyl-15-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 14-azabicyclo[11.2.1]pentadeca-13(16),15-diene;

2-(2-Ηydroxy-«-butyl)-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- - ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-(2-Chloro-«-butyl)-ll-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

2-Butyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; ₁₀ l l-((3-Ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Propyl-ll-((3-ethoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-n-Pentyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-B enzyl- 11 -((3-ethoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; ₂„ 2-Ethyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-ll(14),13-diene;

13-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- ₉ azabicyclo[9.2.1 jtetradeca- 11(14), 13-diene;

2-Ethyl- 12-methyl- 13-((3-benzyloxy-5-(l -methyl- lH-ρynol-2-yl)-2H-pynol- 2-ylidene)methyl)-12-azabϊcyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Ethyl-12-methyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 12-azabicyclo[9.2.1 jtetradeca- 11 ( 14), 13-diene; ₃₀ 2-«-Proρyl-l 3-((3 -benzyloxy-5-( lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)- 12-azabicyclo[9.2.1 Jtetradeca- 11 (14), 13-diene; and

2-n-Butyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene, or a pharmaceutically acceptable salt thereof.

35

8. A compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, ₅ -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR,₀R_πR₁₂, -C(O)CH₃, -C(O)C₆H_s, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₃ is selected from the group consisting of -H, C,-C_I2 straight chain alkyl, ₀ -CH(R₁₄)(R₁₅) wherein R,₄ and R₁₅ are independently C,-C,₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups; - R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R,, and R,₂ are independently C,-C₃ straight or branched chain alkyl;

R,₆ and R,₇ are -H; and m is an integer ranging from 1 to 5; „ with the proviso that the compound of Formula (I) is not: butyl-meta-cycloheptylprodiginine, metacycloprodigiosin,

4-ethoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2 -bi-l H-pynole, or 4-propoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi-l H-pynole. 5

9. The composition of claim 8, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, and -CH₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; _r R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl,

R,₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Foimula (I) is not: _{1 n} butyl-meta-cycloheptylprodiginine, metacycloprodigiosin,

. _<-

10. The composition of claim 8, wherein, in the compound of Formula (I): each R, is -H;

R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, and -CH₂C₆H₅; _f) R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: butyl-meta-cycloheptylprodiginine, metacycloprodigiosin, _{9 <}- 4-ethoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi-l H-pynole, or 4-propoxy-5-((3,5-nonamethylene-2H-pynol-2-ylidene)methyl)-2, 2'-bi-l H-pynole.

11. The composition of claim 8, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, and -CH₃; 3Q R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; ₃₅ with the proviso that when m is 3, R₃ is not -CH₂CH₃ and when m is 1, R₃ is not -(CH₂)₃CH₃.

12. The composition of claim 8, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, and -CH₃;

R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, -CH₃, -«-C₃H₇, -t-C₃H₇, straight chain

5 alkyl from C₅H_n to C₁₀H₂„ (l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl and (l-chloro)butyl;

R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5.

10

13. The composition of claim 8, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, and -CH₃; R₂is selected from the group consisting of -CH₃, and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl;

15 R₁₆ and R,₇ are -H; and m is 2, 4 or 5.

14. The composition of claim 8, wherein the compound of Formula (I) is selected from the group consisting of:

20

2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; l l-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1 ]dodeca-9(12),l 1-diene; ₂₅ 2-Methyl-ll-((3-methoxy-5-(lH-ρynol-2-yl)-2H-ρynol-2-ylidene)methyl)-

10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

2-tt-Propyl- 11 -((3-methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-n-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 3₀ 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-«-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; ₃₅ (R)-2-n-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; (S)-2-«-Butyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(12), 11 -diene;

(R)-2-«-Butyl-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- . ylidene)methyl)- 10-azabicyclo[7.2.1 ] dodeca-9( 12), 11 -diene;

(S)-2-Ethyl-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),ll-diene;

(R)-2-Ethyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; ₁₀ (S)-2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ] dodeca-9( 12), 11 -diene;

(S)-2-«-Propyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ^ ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-«-Propyl-l 1 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9( 12), 11 -diene;

2-Methyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene; ₂₀ 2-Ethyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-l l- azabicyclo[8.2.1]trideca-10(13),12-diene;

2-«-Propyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-«-Butyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- ₂₅ 1 l-azabicyclo[8.2.1]trideca-10(13),12-diene;

12-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-l l- azabicyclo[8.2.1]trideca-10(13),12-diene; ₃₀ 2-Methyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

13-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2. l]tetradeca-l 1 (14), 13-diene;

2-Ethyl-12-methyl-13-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- 3_^. 2-ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene; 2-Ethyl-12-methyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 12-azabicyclo[9.2.1 jtetradeca- 11 (14), 13-diene;

2-n-Propyl-13-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-n-Butyl-13-((3-methoxy-5-(lH-ρynol-2-yl)-2H-ρynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1 jtetradeca- 1 l(14),13-diene;

14-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-13- azabicyclo[10.2.1]pentadeca-12(15),14-diene;

2-Butyl-l l-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),ll-diene;

2-Butyl- 11 -((3-methoxy-5-(l -methyl- lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-methyl- 10-azabicyclo[7.2.1 ]dodeca-9(12), 11 -diene;

2-Butyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)-10- - methyl-10-azabicyclo[7.2.1jdodeca-9(12),l 1-diene;

2-Ethyl- 11 -((3 -benzyloxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl- 11 -((3 -hydroxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2. ljdodeca-9(12),l 1-diene; 2-Butyl-ll-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

11 -((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

2-Methyl-ll-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),ll-diene;

2-»-Propyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l 0-azabicyclo[7.2. l]dodeca-9(12), 11-diene;

2-«-Pentyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9( 12), 11 -diene; ₀ 2-Benzyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)-

10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

15-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-14- ^ azabicyclo[l 1.2.1]pentadeca-13(16),15-diene; 2-Methyl-15-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 14-azabicyclo[11.2.1]pentadeca-13(16),15-diene;

2-(2-Ηydroxy-«-butyl)- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pyrrol-2- ^ ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-(2-Chloro-n-butyl)-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1jdodeca-9(12),l 1-diene;

2-Butyl- 11 -((3 -ethoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; _1Q l l-((3-Ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Propyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- . _<. 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-n-Pentyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1jdodeca-9(12),l 1-diene;

2-Benzyl- 11 -((3 -ethoxy-5 -( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; ₂„ 2-Ethyl-l l-((3-ethoxy-5-(lH-ρynol-2-yl)-2H-p>τrol-2-ylidene)methyl)-10- azabicydo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl- 13-((3-benzyloxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

13-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- ₉ azabicyclo[9.2.1 jtetradeca- 11 (14), 13-diene;

2-Ethyl-12-methyl-13-((3-benzyIoxy-5-(l-methyl-lH-pynol-2-yI)-2H-pynol- 2-ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Ethyl-12-methyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene; ₃ „ 2-R-Propyl- 13 -((3-benzyloxy-5 -( lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene; and

2-n -Butyl- 13 -((3 -benzyloxy-5-( 1 H-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene , or a pharmaceutically acceptable salt thereof.

35

15. A method for treating or preventing cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (I): . _ each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃,

-CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R„R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; _f( R₃ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl,

-CH(R₁₄)(R₁₅) wherein R,₄ and R₁₅ are independently C,-C,₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, ₉ _ methoxyl, or trifluoromethyl groups;

R,, and R,₂ are independently C,-C₃ straight or branched chain alkyl; m is an integer ranging from 1 to 5; and 3₀ when m is 3 and R₂ is -CH₂CH₃, then R,₆ is -H or -CH₃ and R,₇ is -H; when m is 3 and R₂ is -CH₃, then R_I6 is -H or -CH₃ and R,₇ is -H or -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R,₆ and R,₇ are -H only; with the proviso that the compound of Formula (I) is not: ,.,. metacycloprodigiosin.

16. The method of claim 15, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; _ R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl,

-CH₂C₆H₅, -SiR,₀R„R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tefrahydropyranyI, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₃ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH(R_I4)(R₁₅) wherein R₁₄ and R₁₅ are independently C,-C₁₂ straight chain alkyl, -C(O)C,- - „ C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H_S, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups;

R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl ₁₅ and -C₆H₅;

R_π and R_I2 are independently C,-C₃ straight or branched chain alkyl; and R,₆ and R,₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: _n metacycloprodigiosin.

17. The method of claim 15, wherein the compound of Formula (I) is butyl- meta-cycloheptylprodiginine or a pharmaceutically acceptable salt thereof.

₉ ,

18. The method of claim 15 , wherein, in the compound of Formula (I) : each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, (l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; 3_n R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: metacycloprodigiosin.

35

19. The method of claim 15, wherein, in the compound of Formula (I): each R, is -H;

R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C₁₀ sfraight chain alkyl, and -CH₂C₆H₅;

R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Fonnula (I) is not: metacycloprodigiosin.

10

20. The method of claim 15, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅;

₁ , R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl,

-CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R₁₆ and R,₇ are -H; and m is an integer ranging from 1 to 5. with the proviso that when m is 3, R₃ is not -CH₂CH₃ and when m is 1, R₃ is not 0 ^"(^CH2^^CH3-

21. The method of claim 15, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅;

₉ - R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl,

(l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R,₆ and R,₇ are -H; and m is an integer ranging from 1 to 5.

22. The method of claim 15, wherein, in the compound of Formula (I):

30 each R, is independently selected from the group consisting of -H, and -CH₃; R₂is selected from the group consisting of -CH₃, and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl), and (l-chloro)butyl; _ - R₁₆ and R,₇ are -H; and m is 2, 4 or 5.

23. The method of claim 15 , wherein, in the compound of Formula (I) : each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, -(CH₂)₂CH₃, and

_<- -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydxoxy)butyl, and (l-chloro)butyl; m is an integer ranging from 1 to 5; when m is 3 and R₂is -CH₃, then R₁₆is selected from the group consisting of -H, and „ -CH₃ and R₁₇ is selected from the group consisting of -H, and -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R,₆ and R,₇ are -H only; with the proviso that the compound of Formula (I) is not: metacycloprodigiosin.

15

24. The method of claim 15, wherein, in the compound of Formula I is selected from the group consisting of:

2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2. l]dodeca-9(12),l 1-diene; ₀ l l-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(l 2), 11-diene;

2-«-Propyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- _<. 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-n-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Benzyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; ₃₀ (S)-2-«-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 jdodeca-9(l 2), 11 -diene;

(R)-2-«-Pentyl- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2. l]dodeca-9(12), 11 -diene;

(S)-2-/z-Butyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ₃₅ ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; (R)-2-R-Butyl- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

(S)-2-Ethyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(12), 11 -diene;

(S)-2-Methyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; ₁₀ (R)-2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(12), 11 -diene;

(S)-2-«-Propyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-«-Propyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ^ ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),ll-diene;

2-Ethyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-ll- azabicyclo[8.2.1]trideca-10(13),12-diene; ₂₀ 2-n-Propyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-«-Pentyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- _i_ l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

12-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 11 - azabicyclo[8.2.1jtrideca-10(13),12-diene;

2-Methyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1 jtetradeca- 11 (14), 13-diene; ₃₀ 13-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2.1jtetradeca-l l(14),13-diene;

2-Ethyl-12-methyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- _ - ylidene)methyl)- 12-azabicyclo[9.2.1 jtetradeca- 11 ( 14), 13 -diene; 2-«-Propyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-n-Butyl-13-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- _c 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Butyl- 11 -((3-methoxy-5-(l -methyl- lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 Jdodeca-9( 12), 11 -diene; _{1 Q} 2-Butyl-l l-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-methyl- 10-azabicyclo [7.2.1 j dodeca-9( 12), 11 -diene;

2-Butyl- 11 -((3-methoxy-5-( lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- 10- methyl-10-azabicyclo[7.2.1jdodeca-9(12),l 1-diene;

2-Ethyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- . _ 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; _9π l l-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl- 11 -((3-benzyloxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Proρyl-l l-((3-benzyloxy-5-(lH-ρynol-2-yl)-2H-pynol-2- _<- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Pentyl- 11 -((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(l 2), 11 -diene;

2-Benzyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1jdodeca-9(12),l 1-diene; ₃₀ 2-Methyl-14-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-

13-azabicyclo[10.2.1]pentadeca-12(15),14-diene;

15 -((3 -Methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 14- azabicyclo[11.2.1]pentadeca-13(16),15-diene;

2-Methyl-15-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- -j ^ 14-azabicyclo[l 1.2.1]pentadeca-13(16),15-diene; 2-(2-Hydroxy-n-butyl)-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 Jdodeca-9( 12), 11 -diene;

2-(2-Chloro-n-butyl)-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pyrrol-2- _<. ylidene)methyl)-10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

2-Butyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2. l]dodeca-9(12),l 1-diene; l l-((3-Ethoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)-10- azabicyclo[7.2.1jdodeca-9(12),l 1-diene;

2-Methyl- 11 -((3-ethoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-n-Propyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Pentyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

2-Ethyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2. l]dodeca-9(12),l 1-diene; _2Q 2-Methyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2.1Jtetradeca-ll(14),13-diene;

13-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2.1Jtetradeca-ll(14),13-diene;

2-Ethyl-12-methyl-13-((3-benzyloxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- ₉ _ 2-ylidene)methyl)- 12-azabicyclo[9.2.1 jtetradeca- 11(14), 13-diene;

2-Ethyl-12-methyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-«-Propyl-13-((3-benzyloxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)- 12-azabicyclo[9.2.1 Jtetradeca- 11 (14), 13-diene; and ₃₀ 2-R-Butyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2.1Jtetradeca-l l(14),13-diene, or a pharmaceutically acceptable salt thereof.

35

25. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising contacting a cancer cell or neoplastic cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (I): ₁ , each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃,

-CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R.*R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃; „ R₃ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl,

-CH(R₁₄)(R₁₅) wherein R₁₄ and R₁₅ are independently C,-C₁₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, ₉ methoxyl, or trifluoromethyl groups;

R_u and R₁₂ are independently C,-C₃ straight or branched chain alkyl; m is an integer ranging from 1 to 5; 3 when m is 3 and R₂ is -CH₂CH₃, then R,₆ is -H or -CH₃ and R,₇ is -H; when m is 3 and R₂ is -CH₃, then R,₆ is -H or -CH₃ and R,₇ is -H or -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R,₆ and R,₇ are -H only; with the proviso that the compound of Formula (I) is not: _ metacycloprodigiosin.

26. The method of claim 25, wherein the compound of Formula (I) is butyl-meta-cycloheptylprodiginine or a pharmaceutically acceptable salt thereof.

_<.

27. The method of claim 25, wherein, in the compound the compound of

Formula (I): each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

* R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, ₁₀ -CH₂C₆H₅, -SiR₁₀R_πR,₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₃ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH(R,₄)(R,₅) wherein R,₄ and R,₅ are independently C,-C,₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain ₁ , alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the

R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅; _9n R_n and R,₂ are independently C,-C₃ straight or branched chain alkyl; and

R,₆ and R,₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: metacycloprodigiosin.

25

28. The method of claim 25, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, and -CH₃;

R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl,

3„ (l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; m is an integer ranging from 1 to 5; with the proviso that the compound of Formula (I) is not: metacycloprodigiosin.

35

29. The method of claim 25, wherein, in the compound of Formula (I): each R, is -H;

R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, and -CH₂C₆H₅;

10

30. The method of claim 25, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl,

-CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl;

R₁₆ and R,₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that when m is 3, R₃ is not -CH₂CH₃ and when m isl, R₃ is not -(CH₂)₃CH₃.

20

31. The method of claim 25 , wherein, in the compound of Formula (I) : each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, _?J- (l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R₁₆ and R,₇ are -H; and m is an integer ranging from 1 to 5.

32. The method of claim 25, wherein, in the compound of Formula (I): __n each R, is independently selected from the group consisting of -H, and -CH₃;

R₂is selected from the group consisting of -CH₃, and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R₁₆ and R₁₇ are -H; and _o _ m is 2, 4 or 5.

33. The method of claim 25, wherein, in the compound of Formula (I) each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, -(CH₂)₂CH₃, and

. -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydxoxy)butyl, and (l-chloro)butyl; m is an integer ranging from 1 to 5; when m is 3 and R₂ is -CH₃, then R₁₆ is selected from the group consisting of -H, and - „ -CH₃ and R,₇ is selected from the group consisting of -H, and -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R,₆ and R,₇ are -H only; with the proviso that the compound of Formula (I) is not: metacycloprodigiosin.

15

34. The method of claim 25, wherein the compound of Formula I is selected from the group consisting of:

2-Ethyl- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2. l]dodeca-9(12),l 1-diene; ₂₀ ll-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl- 11 -((3 -methoxy-5-( 1 H-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-n-Propyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- _9<- 10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

2-w-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Benzyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; ₃₀ (S)-2-n-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

(R)-2-R-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; .

(S)-2-«-Butyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- - ,. ylidene)methyl)-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene; (R)-2-n-Butyl-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

(S)-2-Ethyl- 11 -((3 -methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

(S)-2-Methyl-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo [7.2.1] dodeca-9 ( 12), 11 -diene;

(R)-2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

(S)-2-n-Propyl-ll-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

(R)-2-n-Propyl-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-Ethyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)-l l- azabicyclo[8.2.1]trideca-10(13),12-diene; „ 2-R-Propyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1Jtrideca-10(13),12-diene;

2-R-Butyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-R-Pentyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- - l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

12-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-ll- azabicyclo[8.2.1]trideca-10(13),12-diene;

2-Methyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-ll(14),13-diene; ₀ 13-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Ethyl-12-methyI-13-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- 2-ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Ethyl- 12-methyl- 13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- _ ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene; 2-n-Propyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-ll(14),13-diene;

2-n-Butyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- _<. 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

14-((3-Methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)-13- azabicyclo[10.2.1]pentadeca-12(15),14-diene;

2-Butyl-ll-((3-methoxy-5-(l-methyl-lH-ρynol-2-yl)-2H-ρynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; _1Q 2-Butyl-l l-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-methyl-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl- 11 -((3 -methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyI)- 10- methyl-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Ethyl-l l-((3-benzyloxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- . _j. 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl- 11 -((3-hydroxy-5-(lH-pynol-2-yl)-2H-ρynol-2-yIidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl- 11 -((3 -benzyloxy-5 -( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene; _2Q 11 -((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-«-Proρyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-ρynol-2- „ ylidene)methyl)-l 0-azabicyclo[7.2.1 Jdodeca-9(12), 11 -diene;

2-R-Pentyl-ll-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-ρynol-2- ylidene)methyl)-10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

2-Benzyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; ₃₀ 2-Methyl-14-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

13-azabicyclo[10.2.1]pentadeca-12(15),14-diene;

2-Methyl-15-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 3 _ 14-azabicyclo[l 1.2.1]pentadeca-13(16),15-diene; 2-(2-Hydroxy-R-butyl)-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-(2-Chloro-R-butyl)-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pyrrol-2- - ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; l l-((3-Ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; ₁₀ 2-Methyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-n-Propyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(l 2), 11-diene;

2-R-Pentyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- .. _ 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Benzyl- 11 -((3-ethoxy-5 -( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Ethyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2. l]dodeca-9(12),l 1-diene; ₂₀ 2-Methyl-13-((3-benzyloxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2.1Jtetradeca-l l(14),13-diene;

2-Ethyl-12-methyl-13-((3-benzyloxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- - 2-ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-ll(14),13-diene;

2-Ethyl-12-methyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 12-azabicyclo [9.2.1] tetradeca- 11 ( 14), 13 -diene;

2-«-Propyl-13-((3-benzyloxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene; and ₃₀ 2-R-Butyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)-

12-azabicyclo[9.2.1 Jtetradeca- 11(14), 13-diene, or a pharmaceutically acceptable salt thereof.

35

35. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR_I0R„R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₃ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, 0 -CH(R₁₄)(R₁₅) wherein R,₄ and R,₅ are independently C,-C,₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyI, -(3-pyridyl)methyI, -(4-pyridyl)methyl, and -CH₂C₆H₅, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, _<- methoxyl, or trifluoromethyl groups;

R,, and R,₂ are independently C,-C₃ straight or branched chain alkyl; m is an integer ranging from 1 to 5; and „ when m is 3 and R₂ is -CH₂CH₃, then R,₆ is -H or -CH₃ and R,₇ is -H; when m is 3 and R₂ is -CH₃, then R,₆ is -H or -CH₃ and R,₇ is -H or -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R₁₆ and R,₇ are -H only.

_<-

36. The method of claim 35 , wherein the compound of Formula (I) is butyl- meta-cycloheptylprodiginine or a pharmaceutically acceptable salt thereof.

37. The method of claim 35, wherein the compound of Formula (I) is metacycloprodigiosin or a pharmaceutically acceptable salt thereof.

-

38. The method of claim 35, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R„R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and ₁₀ -C(O)OCH₂CCl₃;

R₃ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH(R₁₄)(R₁₅) wherein R,₄ and R,₅ are independently C,-C₁₂ straight chain alkyl, -C(O)C_r C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl,. -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the _{1 <}. -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups;

R_u and R₁₂ are independently Cι-C₃ straight or branched chain alkyl; and ₉₍, R₁₆ and R,₇ are -H; and m is an integer ranging from 1 to 5.

39. The method of claim 35, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, and -CH₃; - R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

30

40. The method of claim 35, wherein, in the compound of Formula (I): each R, is -H; and

R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, and

35 -CH₂C₆H₅;

R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5.

41. The method of claim 35 , wherein, in the compound of Formula (I) :

„ each R, is independently selected from the group consisting of -H, and -CH₃;

R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R₁₆ and R,₇ are -H; and 4 m is an integer ranging from 1 to 5; with the proviso that when m is 3, R₃ is not -CH₂CH₃ and when m isl, R₃ is not -(CH₂)₃CH₃.

42. The method of claim 35, wherein, in the.compound of Formula (I): each R, is independently selected from the group consisting of -H, and -CH₃;

₁ - R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, (l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R_]6 and R,₇ are -H; and m is an integer ranging from 1 to 5.

20

43. The method of claim 35 , wherein, in the compound of Formula (I) : each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, -CH₂C₆H₅, ₉_- butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R,₆ and R₁₇ are -H; and m is 2, 4 or 5.

44. The method of claim 35, wherein, in the compound of Formula (I): 3„ each R, is independently selected from the group consisting of -H, and -CH₃;

R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydxoxy)butyl, and (l-chloro)butyl; 3_<. m is an integer ranging from 1 to 5; when m is 3 and R₂is -CH₃, then R,₆is selected from the group consisting of -H, and -CH₃ and R,₇is selected from the group consisting of -H, and -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R,₆ and R,₇ are -H only.

45. The method of claim 35 , wherein the compound of Formula I is selected from the group consisting of:

2-Ethyl- 11 -((3 -methoxy-5-( lH-p vrrol-2- yl)-2#-p ynol-2-ylidene)methyl)- 10- „ azabicyclo[7.2.1]dodeca-9(12),ll-diene; l l-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; ₅ 2-n-Propyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)-

10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-R-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Benzyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-n-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

(R)-2-«-Pentyl- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynoI-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(5)-2-«-Butyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12)_>l 1-diene;

(R)-2-rc-Butyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(»S -2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- ₀ 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(l 2), 11 -diene;

(S)-2-Methyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9(l 2), 11 -diene; ₅ (R)-2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9( 12), 11 -diene; (S)-2-n-Propyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(R)-2-R-Propyl-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- - ylidene)methyl)-10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

2-Ethyl- 12-((3-methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 11 - azabicyclo[8.2.1]trideca-10(13),12-diene; ₁₀ 2-R-Propyl- 12-((3 -methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-«-Butyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-«-Pentyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- .. _ l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-Methyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1Jtetradeca-l l(14),13-diene;

₂ 13-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12- azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Ethyl-12-methyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ₉ ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-R-Propyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1 Jtetradeca- 11(14), 13-diene;

2-n-Butyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1 Jtetradeca- 11 (14), 13-diene; ₃₀ 14-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-13- azabicyclo[10.2.1]pentadeca-12(15),14-diene;

2-Butyl-l l-((3-methoxy-5-(l-methyl-lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo [7.2.1 ]dodeca-9( 12), 11 -diene;

2-Butyl-ll-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol-2-

3 ylidene)methyl)- 10-methyl- 10-azabicyclo[7.2.1 ]dodeca-9(l 2), 11 -diene; 2-Butyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- methyl-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Ethyl-ll-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl-l l-((3-hydroxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

2-Butyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; _{1 Q} l l-((3-Benzyloxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo [7.2.1] dodeca-9( 12) , 11 -diene;

2-Methyl- 11 -((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-R-Propyl-l 1 -((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- - _ ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-R-Pentyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

2-Benzyl-ll-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; _Q 2-Methyl-14-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

13-azabicyclo[10.2.1]pentadeca-12(15),14-diene;

2-Methyl-15-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- _<- 14-azabicyclo[l 1.2.1]pentadeca-13(16),15-diene;

2-(2-Ηydroxy-R-butyl)-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-(2-Chloro-R-butyl)-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene; ₃₀ 2-Butyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; l l-((3-Ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl- 11 -((3 -ethoxy-5-( lH-pynoI-2-yl)-2H-pynol-2-ylidene)methyl)- 10- 3 - azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 2-R-Propyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1Jdodeca-9(12),l 1-diene;

2-R-Pentyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Benzyl-l l-((3-ethoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Ethyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; ₀ 2-Methyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2.1]tetradeca-ll(14),13-diene;

13-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2. l]tetradeca-l 1(14), 13-diene;

2-Ethyl-12-methyl-13-((3-benzyloxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- _. 2-ylidene)methyl)-12-azabicyclo[9.2. l]tetradeca-l l(14),13-diene;

2-Ethyl- 12-methyl- 13-((3-benzyloxy-5-(lH-pynol-2-yI)-2H-pynol-2- ylidene)methyl)-12-azabicyclo[9.2.1]tetradeca-l 1(14), 13-diene;

2-R-Propyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-12-azabicyclo[9.2. l]tetradeca-l 1(14), 13-diene; and „ 2-R-Butyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

12-azabicyclo[9.2.1]tetradeca-l 1(14), 13-diene, or a pharmaceutically acceptable salt thereof.

46. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (I):

₅ or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₃ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH(R₁₄)(R_I5) wherein R,₄ and R_]5 are independently C,-C₁₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C,-C₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the -CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups;

R,, and R₁₂ are independently C,-C₃ straight or branched chain alkyl; m is an integer ranging from 1 to 5; and when m is 3 and R₂ is -CH₂CH₃, then R₁₆is -H or -CH₃ and R,₇ is -H; when m is 3 and R₂ is -CH₃, then R₁₆ is -H or -CH₃ and R₁₇ is -H or -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R₁₆ and R₁₇ are -H only.

47. The method of claim 46, wherein the compound of Formula (I) is butyl- meta-cycloheptylprodiginine or a pharmaceutically acceptable salt thereof.

48. The method of claim 46, wherein the compound of Formula (I) is metacycloprodigiosin or a pharmaceutically acceptable salt thereof.

49. The method of claim 46, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR.₀R..R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₃ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH(R₁₄)(R₁₅) wherein R₁₄ and R₁₅ are independently C,-C,₂ straight chain alkyl, -C(O)C,- C₉ straight chain alkyl, -CH(OH)C_rC₉ straight chain alkyl, -CH(C1)C,-C₉ straight chain alkyl, -(2-pyridyl)methyl, -(3-pyridyl)methyl, -(4-pyridyl)methyl, and -CH₂C₆H₅, the - CH₂C₆H₅ being unsubstituted or substituted on phenyl with one cyano or one or more halo, methoxyl, or trifluoromethyl groups;

R,₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5.

10

50. The method of claim 46, wherein, in the compound of.Formula (I): each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl,

₁ - (l-methyl)butyl, -CH₂C₆H_S, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R₁₆ and R₁₇ are -H; and m is an integer ranging from 1 to 5.

51. The method of claim 46, wherein, in the compound of Formula (I): _n each R, is -H;

R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, and -CH₂C₆H₅;

R₁₆ and R₁₇ are -H; and -_c m is an integer ranging from 1 to 5.

52. The method of claim 46, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅;

3„ R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl,

-CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl;

R_I6 and R₁₇ are -H; and m is an integer ranging from 1 to 5; with the proviso that when m is 3, R₃ is not -CH₂CH₃ and when m isl, R₃ is not -(CH₂)₃CH₃.

35

53. The method of claim 46, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, and -CH₂C₆H₅; R₃ is selected from the group consisting of -H, C,-C,₀ sfraight chain alkyl,

5 (l-methyl)butyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; R₁₅ and R_I7 are -H; and m is an integer ranging from 1 to 5.

- _π

54. The method of claim 46, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, and -CH₃;

R₂is selected from the group consisting of -CH₃, and -CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C₁₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydroxy)butyl, and (l-chloro)butyl; . .. R₁₆ and R₁₇ are -H; and m is 2, 4 or 5.

55. The method of claim 46, wherein, in the compound of Formula (I): each R, is independently selected from the group consisting of -H, and -CH₃; ₉„ R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, -(CH₂)₂CH₃, and

-CH₂C₆H₅;

R₃ is selected from the group consisting of -H, C,-C,₀ straight chain alkyl, -CH₂C₆H₅, butyroyl, (l-hydxoxy)butyl, and (l-chloro)butyl; mis an integer ranging from 1 to 5; _ when m is 3 and R₂ is -CH₃, then R,₆ is selected from the group consisting of -H, and

-CH₃ and R,₇is selected from the group consisting of -H, and -COOEt; and when m is other than 3 and R₂ is other than -CH₃ or -CH₂CH₃, then R,₆ and R,₇ are -H only.

3₀

56. The method of claim 46, wherein the compound of Formula I is selected from the group consisting of:

2-Ethyl-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2. l]dodeca-9(12),l 1-diene; l l-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- 3 azabicyclo[7.2.1]dodeca-9(12),l 1-diene; 2-Methyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-R-Propyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- ₅ 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-R-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),ll-diene;

2-Benzyl-ll-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; _{j Q} (S)-2-R-Pentyl- 11 -((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l 0-azabicyclo[7.2.1 ]dodeca-9(l 2), 11 -diene;

(R)-2-R-Pentyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynoI-2- ylidene)methyl)- 10-azabicyclo [7.2.1 ]dodeca-9( 12), 11 -diene;

(S)-2-R-Butyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- . ,. ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l l-diene;

(R)-2-R-Butyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-Ethyl-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; ₂₀ (R)-2-Ethyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

(S)-2-Methyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9( 12), 11 -diene;

(R)-2-Methyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ,- ylidene)methyl)- 10-azabicyclo[7.2.1 ]dodeca-9( 12), 11 -diene;

(S)-2-R-Propyl-l l-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 10-azabicyclo[7.2. l]dodeca-9(l 2), 11 -diene;

(R)-2-R-Propyl-ll-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l 0-azabicyclo[7.2. l]dodeca-9(12), 11 -diene; ₃₀ 2-Methyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-Ethyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-l l- azabicyclo[8.2.1]trideca-10(13),12-diene;

2-R-Propyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 3_ l l-azabicyclo[8.2.1]trideca-10(13),12-diene; 2-R-Butyl-12-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

2-R-Pentyl- 12-((3 -methoxy-5-( lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)- ^ l l-azabicyclo[8.2.1]trideca-10(13),12-diene;

12-((3 -Methoxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 11 - azabicyclo[8.2.1]trideca-10(13),12-diene;

2-Methyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l 1(14), 13-diene; _{1 Q} 13-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-Ethyl-12-methyl-13-((3-methoxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- 2-ylidene)methyl)- 12-azabicyclo[9.2. ljtetradeca- 11(14), 13-diene;

2-Ethyl-12-methyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- . ~ ylidene)methyl)-12-azabicyclo[9.2. ljtetradeca- 1 l(14),13-diene;

2-7z-Propyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene;

2-R-Butyl-13-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 12-azabicyclo[9.2.1]tetradeca-l l(14),13-diene; _2Q 14-((3-Methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-13- azabicyclo[10.2.1]pentadeca-12(15),14-diene;

2-Butyl- 11 -((3-methoxy-5-( 1 -methyl- lH-pynol-2-yl)-2H-pynoI-2- ₉ - ylidene)methyl)- 10-methyl- 10-azabicyclo[7.2.1 ]dodeca-9(12), 11 -diene;

2-Ethyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),ll-diene; ₃₀ 2-Butyl-l l-((3-hydroxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Butyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; l l-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- 3 r azabicyclo[7.2.1 ]dodeca-9(12), 11 -diene; 2-Methyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-R-Proρyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- , ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-R-Pentyl- 11 -((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Benzyl-l l-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene; ₁₀ 2-Methyl-14-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-

13-azabicyclo[10.2.1]pentadeca-12(15),14-diene;

15-((3-Methoxy-5-(lH-ρynol-2-yl)-2H-ρynol-2-ylidene)methyl)-14- azabicyclo[11.2.1]pentadeca-13(16),15-diene;

2-Methyl-15-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- _ _e 14-azabicyclo[11.2.1]pentadeca-13(16),15-diene;

2-(2-Ηydroxy-R-butyl)-l l-((3-methoxy-5-(lH-pynoI-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-(2-Chloro-R-butyl)-l l-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)-10-azabicyclo[7.2. l]dodeca-9(12),l 1-diene;

2-Butyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene; l l-((3-Ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2. l]dodeca-9(l 2), 11-diene;

2-Methyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- ₉ - azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-R-Proρyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-R-Pentyl-ll-((3-ethoxy-5-(lH-pynol-2-yl)-2H-ρynol-2-ylidene)methyl)- 10-azabicyclo[7.2.1]dodeca-9(12),ll-diene; ₃₀ 2-Benzyl-l l-((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-10- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Ethyl-l 1 -((3-ethoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-l 0- azabicyclo[7.2.1]dodeca-9(12),l 1-diene;

2-Methyl- 13-((3-benzyloxy-5-( lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)- 3_ 12-azabicyclo[9.2.1]tetradeca-l 1(14), 13-diene; 13-((3-Benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-12- azabicyclo[9.2. l]tetradeca-l l(14),13-diene;

2-Ethyl-12-methyl-13-((3-benzyloxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- 2-ylidene)methyl)- 12-azabicyclo[9.2.1 jtetradeca- 11(14), 13-diene;

2-Ethyl- 12-methyl- 13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l 2-azabicyclo[9.2. ljtetradeca- 11(14), 13-diene;

2-R-Propyl-13-((3-benzyloxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 12-azabicyclo [9.2.1] tetradeca- 11 ( 14), 13 -diene; and _Q 2-n-Butyl-13-((3-benzyloxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-

57. A compound having the general Formula (II): 5

II or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -Η, -CΗ₃, -CH₂CH₃, ₅ -CH₂C₆H_S, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅. and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H_S, -SiR,₀R_nR_I2, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₄ is selected from the group consisting of -H and C,-C,₂ straight chain alkyl; ^ R₅ is selected from the group consisting of -H, C,-C₄ sfraight chain alkyl and -C₆H₅;

R₁₀ is selected from the group consisting of -C,-C₄, straight or branched chain alkyl and -C₆H_S;

R, , and R,₂ are independently C,-C₃ straight or branched chained alkyl; and n is an integer ranging from 1 to 6; ^ with the proviso that the compound of Formula (II) is not: cycloprodigiosin or

4-ethyl-2,4,5,6-tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl-)-2H-pynol-2- ■ ylidene)methyl)- 1 -methyl-cyclopenta(c)pynole.

58. The compound of claim 57, wherein:

R, is selected from the group consisting of -H, and -CH₃;

R₄ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃;

- „ R₅ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and n is an integer ranging from 1 to 3. with the proviso that the compound of Formula (II) is not: cycloprodigiosin or 4-ethyl-2,4,5,6-tetrahydro-3-((3-methoxy-5-(lH-ρynol-2-yl-)-2H-pynol-2-

- _ ylidene)methyl)-l-methyl-cyclopenta(c)pynole.

59. The compound of claim 57, wherein:

R, is selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; _n R₄ and R₅ are independently selected from the group consisting of -H, -CH₃, and

-H₂CH₃; and n is an integer ranging from 1 to 3.

60. The compound of claim 57, wherein: _- R, is selected from the group consisting of -H, and -CH₃;

R₄ is -H;

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -R-C₄H₉, and -C₆H₅; and 3„ n is an integer ranging from 1 to 3.

61. The compound of claim 57, selected from the group consisting of: 4,5,6,7-Tetrahydro-3-((3-benzyloxy-5-(l-methyl-lH-ρynol-2-yl)-2H-pynol-

2-ylidene)methyl)- 1 ,4-dimethyl-2H-isoindole;

35 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-4-ethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- , ylidene)methyl)-4-ethyl- 1 -methyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2- ylidene)methyl)- 1 -ethyl-4-methyl-2H-isoindole; and _1Q 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)-l-ethyl-2H-isoindole, or a pharmaceutically acceptable salt thereof.

62. A composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula (II):

20

II or a pharmaceutically acceptable salts thereof, wherein: each R, is independently selected from the group consisting of -Η, -CΗ₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; _ R₂ is selected from the group consisting of -H, C,-C,₂ sfraight chain alkyl,

-CH₂C₆H₅, -SiR,₀R,.R₁₂, -C(O)CH₃, -C(O)C₆H_s, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₄ is selected from the group consisting of -H and C,-C,₂ straight chain alkyl;

R₅ is selected from the group consisting of -H, C,-C₄ straight chain alkyl and -C₆H₅; ~„ R_I0 is selected from the group consisting of C,-C₄ straight or branched chain alkyl, and -C₆H₅;

R_n and R_]2 are independently selected from the group consisting of -CH₃, -CH₂CH₃, and -C₃H₇; and n is an integer ranging from 1 to 6; with the proviso that the compound of Formula (II) is not:

35 cycloprodigiosin or

63. The composition of claim 62, wherein the compound of Formula (II):

R, is selected from the group consisting of -H, and -CH₃;

R₄ and R₅ are independently selected from the group consisting of -H, -CH₃, and ₀ -CH₂CH₃; n is an integer ranging from 1 to 3. with the proviso that the compound of Formula (If) is not: cycloprodigiosin or

4-ethyl-2,4,5,6-tetrahydro-3-((3-methoxy-5-(lH-ρynol-2-yl-)-2H-pynol-2- ylidene)methyl)-l-methyl-cyclopenta(c)pynole.

64. The composition of claim 62, wherein the compound of Formula (IT): R. is selected from the group consisting of -H, and -CH₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C H₅; „ R₄ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and a C₃-C,₂ straight chain alkyl;

R₅ is -H; and n is an integer ranging from 1 to 3.

-

65. The composition of claim 62, wherein the compound of Formula (II):

R, is selected from the group consisting of -H, and -CH₃;

R₄ is -H;

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -n-C₄H₉, and 0 -C₆H₅; and n is an integer ranging from 1 to 3.

5

66. The composition of claim 62, wherein the compound of Formula (II) is selected from the group consisting of:

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-4-ethyl- 1 -methyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- 0 ylidene)methyl)- 1 ,4-diethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-ρynol-2-yl)-2H-ρynol-2- ylidene)methyl)- 1 -ethyl-4-methyl-2H-isoindole; and

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l-ethyl-2H-isoindole, or a pharmaceutically acceptable salt thereof. 5

67. A method for treating.or preventing a cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a compound of Formula (II):

5

II or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -Η, -CΗ₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; _f) R₂ is selected from the group consisting of -H, C,-C_I2 straight chain alkyl,

-CH₂C₆H₅, -SiR₁₀R_πR,₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₅ is selected from the group consisting of -H, C,-C₄ straight chain alkyl and -C₆H₅; 5 R,₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl, and -C₆H₅;

R,, and R₁₂ are independently selected from the group consisting of C,-C₃ straight or _<_ branched chain alkyl; and n is an integer ranging from 1 to 6; with the proviso that the compound of Formula (II) is not: cycloprodigiosin.

. -

68. The method of claim 67, wherein the compound of Formula (II) is 4-ethyl-

2,4,5 ,6-tetrahydro-3 -((3 -methoxy-5-( 1 H-pynol-2-yl-)-2H-pynol-2-ylidene)methyl)- 1 - methyl-cyclopenta(c)pynole or a pharmaceutically acceptable salt thereof.

69. The method of claim 67, wherein, in the compound of Formula (II): R, is selected from the group consisting of -H, and -CH₃;

15

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ and R₅ are independently selected from the group consisting of -H, -CH₃, and -CH₂CH₃; n is an integer ranging from 1 to 3; with the proviso that the compound of Formula (II) is not: cycloprodigiosin.

70. The method of claim 67, wherein, in the compound of Formula (IT): R, is selected from the group consisting of -H, and -CH₃; _ R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

R₄ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and a C₃-C,₂ sfraight chain alkyl;

R₅ is -H; and n is an integer ranging from 1 to 3.

30

71. The method of claim 67, wherein, in the compound of Formula (II): R, is selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ is -H;

35 R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -R-C₄H₉, and -C₆H₅; and n is an integer ranging from 1 to 3.

72. The method of claim 67, wherein, in the compound of Formula (II):

R, is selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and a C₃-C₁₂ straight _n chain alkyl;

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -n-C₄H₉, and C₆H₅; and n is an integer ranging from 1 to 3; with the proviso that the compound of Formula (II) is not: , cycloprodigiosin.

73. The method of claim 67, wherein, in the compound of Formula (II) is selected from the group consisting of:

4,5,6,7-Tetrahydro-3-((3-benzyloxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- _ 2-ylidene)methyl)- 1 ,4-dimethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)-4-ethyl- 1 -methyl-2H-isoindole; ₅ 4,5,6,7-Tefrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2- ylidene)methyl)- 1 ,4-diethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- 1 -ethyl-4-methyl-2H-isoindole; and

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- „ ylidene)methyl)- 1 -ethyl-2H-isoindole.

35

74. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising a contacting a cancer cell or neoplastic cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (II):

II or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; 5

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R_πR.₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₄ is selected from the group consisting of -H and C,-C₁₂ straight chain alkyl; „ R₅ is selected from the group consisting of -H, C,-C₄ straight chain alkyl and -C₆H₅;

R,, and R₁₂ are independently C C₂ straight or branched chain alkyl; and n is a integer from 1 to 6; with the proviso that the compound of Formula (II) is not: 5 cycloprodigiosin.

75. The method of claim 74, wherein the compound of Formula (II) is 4-ethyl- 2,4,5,6-tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl-)-2H-pynol-2-ylidene)methyl)-l- „ methyl-cyclop enta(c)pynole or a pharmaceutically acceptable salt, thereof.

76. The method of claim 74, wherein, in the compound of Formula (II): R, is selected from the group consisting of -H, and -CH₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; 5 R₄ and R₅ re independently selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and n is an integer ranging from 1 to 3; with the proviso that the compound of Formula (II) is not: cycloprodigiosin.

77. The method of claim 74, wherein, in the compound of Formula (II): R, is selected from the group consisting of -H, and -CH₃; - „ R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

R₅ is -H; and n is an integer ranging from 1 to 3.

15

78. The method of claim 74, wherein, in the compound of Formula (II): R, is selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ is -H; _9π R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -«-C₄H₉, and

-C₆H₅; n is a integer from 1 to 3.

79. The method of claim 74, wherein, in the compound of Formula (II): ₉ - R, is selected from the group consisting of -H, and -CH₃;

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -n-C₄H₉, and _3Q C₆H₅; and n is an integer ranging from 1 to 3; with the proviso that the compound of Formula (II) is not: cycloprodigiosin.

35

80. The method of claim 74, wherein the compound of Formula (It) is selected from the group consisting of:

4,5,6,7-Tetrahydro-3-((3-benzyloxy-5-(l-methyl-lH-pynol-2-yl)-2H-pynol- _<- 2-ylidene)methyl)- 1 ,4-dimethyl-2H-isoindole;

4,5,6, 7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l -ethyl-4-methyl-2H-isoindole; and

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- y!idene)methyl)-l-ethyl-2H-isoindole, or a pharmaceutically acceptable salt thereof.

15

81. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (II):

20

II or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (TT): each R, is independently selected from the group consisting of -Η, -CΗ₃, -CH₂CH₃, _3Q -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₄ is selected from the group consisting of -H and C,-C₁₂ straight chain alkyl; 3_. R₅ is selected from the group consisting of -H, C,-C₄ straight chain alkyl and -C₆H₅; R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl, and -C₆H₅;

R,, and R,₂ are independently C,-C₃ straight or branched chain alkyl; and , n is a integer from 1 to 6.

82. The method of claim 81 , wherein the compound of Formula (II) is cycloprodigiosin or 4-ethyl-2,4,5,6-tetrahydro-3-((3-methoxy-5-(lH-pynol- 2-yl-)-2H-pynol-2-ylidene)methyl)- 1 -methyl-cyclopenta(c)pynole, or a

- _π pharmaceutically acceptable salt thereof.

83. The method of claim 81 , wherein, in the compound of Formula (TT) : R, is selected from the group consisting of -H, and -CH₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ and R₅ are independently selected from the group consisting of -H, -CH₃, and

15 -CH₂CH₃; and n is an integer ranging from 1 to 3.

84. The method of claim 81, wherein, in the compound of Formula (TT): _n R, is selected from the group consisting of -H, and -CFI₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and a C₃-C₁₂ straight chain alkyl;

R₅ is -H; and n is an integer ranging from 1 to 3.

25

85. The method of claim 81 , wherein, in the compound of Formula (TT) :

R, is selected from the group consisting of -H, and -CH₃;

R₄ is -H;

30

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -R-C₄H₉, and -C₆H₅; and n is an integer ranging from 1 to 3.

35

86. The method of claim 81, wherein, in the compound of Formula (TT): R, is selected from the group consisting of -H, and -CH₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; - R₄ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and a C₃-C,₂ straight chain alkyl;

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -R-C₄H₉, and C₆H₅; and n is an integer ranging from 1 to 3.

10

87. The method of claim 81 , wherein the compound of Formula (TT) is selected from the group consisting of:

4,5,6,7-Tetrahydro-3-((3-benzyloxy-5-(l-methyl-lH-ρynol-2-yl)-2H-pynol- 2-ylidene)methyl)- 1 ,4-dimethyl-2H-isoindole; . 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-4-ethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- „ ylidene)methyl)- 1 ,4-diethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2- ylidene)methyl)- 1 -ethyl-4-methyl-2H-isoindole; and

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-l-ethyl-2H-isoindole or a pharmaceutically acceptable salt thereof. 5

88. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (II):

35

II or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; ^ R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl,

-CH₂C₆H₅, -SiR₁₀R„R,₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₅ is selected from the group consisting of -H, C,-C₄ straight chain alkyl and -C₆H₅; ₁ « R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl, and -C₆H₅;

R_π and R,₂ are independently C,-C₃ straight or branched chain alkyl; and n is a integer from 1 to 6.

89. The method of claim 88, wherein the compound of Formula (II) is

15 cycloprodigiosin or 4-ethyl-2,4,5,6-tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl-)-2H- pynol-2-ylidene)methyl)-l-methyl-cyclopenta(c)pynole or a pharmaceutically acceptable salt thereof.

_n

90. The method of claim 88, wherein, in the compound of Formula (II):

R, is selected from the group consisting of -H, and -CH₃;

R₄ and R₅ are independently selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and _<- n is an integer ranging from 1 to 3.

91. The method of claim 88, wherein, in the compound of Formula (TT): R, is selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; 3^ R₄ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and a C₃-C,₂ straight chain alkyl;

R₅ is -H; and n is an integer ranging from 1 to 3.

35

92. The method of claim 88, wherein, in the compound of Formula (TT): R, is selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; ₅ R₄ is -H;

_{ι n}

93. The method of claim 88, wherein, in the compound of Formula (TT):

R, is selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₄ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and a C₃-C_l2 straight chain alkyl; , - R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -R-C₄H₉, and

C₆H₅; and n is an integer ranging from 1 to 3.

94. The method of claim 88, wherein the compound of Formula (TT) is selected ₀ from the group consisting of:

4,5,6,7-Tefrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2- ylidene)methyl)-4-ethyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2- ylidene)methyl)-4-ethyl- 1 -methyl-2H-isoindole;

4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H-ρynol-2- 3„ ylidene)methyl)-l-ethyl-4-methyl-2H-isoindole; and

35

95. A compound having the general Formula (III):

III

10 or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, ₁₅ -SiR₁₀R„R,₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R,₀ is selected from the group consisting of C,-C₆ straight or branched chain alkyl and -C₆H₅; _„ R,, and R,₂ are independently C,-C₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6; with the proviso that the compound of Formula (III) is not: orthobutylcycloheptylprodiginine,

4-methoxy-5-((4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH-pynole), ₂₅ 4-methoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi- 1 H- pynole),

4-ethoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indoI-2-ylidene)methyl)-2,2'-bi-lH- pynole) or

4-propoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH- ₃₀ pynole).

96. The compound of claim 95, wherein: each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; 32 R₅ is selected from the group consisting of -CH₃, -CH₂CH₃; and n is an integer ranging from 1 to 3.

97. The compound of claim 95, selected from the group consisting of 4,5, 6,7- Tetrahydro-3-((3-methoxy-5-(lH-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-5-methyl-lH- indole and 4,5 , 6, 7-Tetrahydro-3 -((3 -methoxy-5-( 1 H-pynol-2-yl)-2H-pynol-2- ylidene)methyl)- lH-indole.

98. A composition comprising a pharmaceutically acceptable carrier and a _ _n therapeutically effective amount of a compound of Formula (IE):

III

or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -Η, -CΗ₃, -CH₂CH₃, ₂₀ -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R„R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₅ is selected from the group consisting of -H, C,-C₆ straight chain alkyl and -C₆H₅; _9.. R,₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R,, and R,₂ are independently C,-C₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6; with the proviso that the compound of Formula (III) is not: 3 „ orthobutylcycloheptylprodiginine;

4-ethoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH- 3_^. pynole) or 4-propoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH- pynole).

99. The composition of claim 98, wherein, in the compound of Formula (III): each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₅ is selected from the group consisting of -CH₃, -CH₂CH₃; and n is an integer ranging from 1 to 3.

100. The composition of claim 98, wherein the compound of Formula (TTT) is selected from the group consisting of: 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2- yl)-2H-pynol-2-ylidene)methyl)-5-methyl- lH-indole and 4,5,6,7-Tetrahydro-3-((3- methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-lH-indole, or a pharmaceutically acceptable salt thereof.

101. A method for treating or preventing a cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention a composition comprising a therapeutically effective amount of a compound of Formula (UI):

HI

or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl,

-CH₂C₆H₅, -SiR,₀R_πR₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₅ is selected from the group consisting of -H, C,-C₆ straight chain alkyl and -C₆H₅; R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅; R,, and R,₂ are independently C,-C₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6.

102. A method of claim 101, wherein the compound of Formula (ΪTT) is selected from the group consisting of: 4-methoxy-5-((4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)- 2,2'-bi-l H-pynole), 4-methoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)- 2,2'-bi-l H-pynole), 4-ethoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)- 2,2'-bi-lH-pynole) and 4-propoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2- ylidene)methyl)-2,2'-bi-l H-pynole), or a pharmaceutically acceptable salt thereof.

10

103. The method of claim 101, wherein, in the compound of Formula (TTT) : each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

- _r R₅ is selected from the group consisting of -CH₃, and -CH₂CH₃; and n is an integer ranging from 1 to 3.

104. The method of claim 101, wherein, in the compound of Formula (TTT): each R, is independently selected from the group consisting of -H, and -CH₃;

₉„ R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

R₅is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -«-C₄H₉, -(CH₂)₅CH_3ι and -C₆H₅; and n is an integer ranging from 1 to 3.

2 105. The method of claim 101, wherein the compound of Formula (TTT) is selected from the group consisting of: 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H- pynol-2-ylidene)methyl)-5-methyl- lH-indole, and 4,5,6,7-Tetrahydro-3-((3-methoxy-5- (lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-lH-indole or a pharmaceutically acceptable salt thereof.

30

35

106. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising a contacting a cancer cell or neoplastic cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (IH):

III

or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

15

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH₂C₆H₅, -SiR,₀R_πR₁₂, -C(O)CH₃, -C(O)C₅H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl,

20 and -C₆H₅;

R,, and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6.

107. The method of claim 106, wherein the compound of Formula (TTT) is selected

25 from the group consisting of: 4-methoxy-5-((4,5,6,7-tetrahydro-2H-indol-2- ylidene)methyl)-2,2'-bi-l H-pynole), 4-methoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2- ylidene)methyl)-2,2'-bi-l H-pynole), 4-ethoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2- ylidene)methyl)-2,2'-bi-lH-pynole) and 4-propoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-

_ _ 2-ylidene)methyl)-2,2'-bi- 1 H-pynole), or a pharmaceutically acceptable salt thereof.

108. The method of claim 106, wherein, in the compound of Formula (TTT): each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

₃₅ R₅ is selected from the group consisting of -CH₃, and -CH₂CH₃; and n is an integer ranging from 1 to 3.

109. The method of claim 106, wherein, in the compound of Formula (111): each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

R₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -«-C₄H₉, -(CH₂)₅CH_3j and -C₆H₅; and n is an integer ranging from 1 to 3.

110. The method of claim 106, wherein the compound of Formula (HI) is selected from the group consisting of: 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H- pynol-2-ylidene)methyl)-5-methyl-lH-indole and 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH- pynol-2-yl)-2H-pynol-2-ylidene)methyl)-lH-indole.

111. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (TTT):

III or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (TTT): each R, is independently selected from the group consisting of -Η, -CΗ₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl,

-CH₂C₆H₅, -SiR,₀R_uR,₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₅ is selected from the group consisting of -H, C,-C₆ straight chain alkyl and -C₆H₅; R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅; R_π and R,₂ are independently C,-C₃ straight or branched chain alkyl; and n is an integer ranging from 1 to 6.

112. The method of claim 111, wherein the compound of Formula (TTT) is selected from the group consisting of: 4-methoxy-5-((4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)- 2,2'-bi-lH-pynole), 4-methoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)- 2,2'-bi-lH-ρynole), 4-ethoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)- 2,2'-bi-lH-pynole) and 4-propoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-

₁ „ ylidene)methyl)-2,2'-bi-l H-pynole), or a pharmaceutically acceptable salt thereof.

113. The method of claim 111, wherein, in the compound of Formula (TTT) : each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

- 2 R₅ is selected from the group consisting of -CH₃, and -CH₂CH₃; n an integer ranging from 1 to 3.

114. The method of claim 111, wherein, in the compound of Formula (IH): each R, is independently selected from the group consisting of -H, and -CH₃; _n R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

R₅is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -R-C₄H₉, -(CH₂)₅CH₃, and -C₆H₅; and n is an integer ranging from 1 to 3.

-

115. The method of claim 111, wherein the compound of Formula (TTT) is selected from the group consisting of: 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H- pynol-2-ylidene)methyl)-5-methyl- IH-indole and 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH- pynol-2-yl)-2H-pynol-2-ylidene)methyl)-lH-indole.

_3Λ

116. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (III), or a pharmaceutically acceptable salt thereof, wherein: each R, is independently selected from the group consisting of -Η, -CΗ₃, -CH₂CH₃,

₃₅ -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR,₀R_nR,₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

10

117. The method of claim 116, wherein the compound of Formula (TTT) is selected from the group consisitng of:

4-methoxy-5-((4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH-pynole), 4-methoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH-pynole), 4-ethoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH-pynole) and

15 4-propoxy-5-(4-hexyl-(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl)-2,2'-bi-lH-pynole), or a pharmaceutically acceptable salt thereof.

118. The method of claim 116, wherein, in the compound of Formula (III): _f) each R, is independently selected from the group consisting of -H, and -CH₃;

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₅ is selected from the group consisting of -CH₃, and -CH₂CH₃; and n is an integer ranging from 1 to 3.

2 119. The method of claim 116, wherein, in the compound of Formula (TTT) : each R, is independently selected from the group consisting of -H, and -CH₃; R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C H₅; R₅is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -C₃H₇, -R-C₄H₉, -(CH₂)₅CH_3I and -C₆H₅; and

_3n n is an integer ranging from 1 to 3.

120. The method of claim 116, wherein the compound of Formula (III) is selected from the group consisting of: 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-pynol-2-yl)-2H- pynol-2-ylidene)methyl)-5-methyl-lH-indole and 4,5,6,7-Tetrahydro-3-((3-methoxy-5-(lH-

35 pynol-2-yl)-2H-pynol-2-ylidene)methyl)-lH-indole, or a pharmaceutically acceptable salt thereof

121. A compound having the general Formula (IV) :

or a pharmaceutically acceptable salt thereof, wherein: . 2 R₂ is selected from the group consisting of -Η, C,-C,₂ straight chain alkyl,

-CΗ₂C₆Η₅, -SiR₁₀R_uR,₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃;

20

R_π and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and p is as integer from 6 to 8; with the proviso that the compound of Formula (TV) is not: cyclononylprodiginine, ₉2 methylcyclooctylprodiginine, methylcyclodecylprodiginine, ethylcyclononylprodiginine, R39FF, R39MF,

30 R39SF, 61 OFF or 610MF.

122. The compound of claim 121, wherein: 3₅ R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; p is an integer ranging from 6 to 8; with the proviso that the compound of Formula (IN) is not: cyclononylprodiginine, methylcyclooctylprodiginine, methylcyclodecylprodiginine, ethylcyclononylprodiginine, R39FF, R39MF, R39SF, 61 OFF or 610MF.

123. The compound of claim 121 wherein:

R₂ is selected from the group consisting of -CH₃; -CH₂CH₃, and -CH₂C₆H₅;

R₆ is -H; and p is an integer of 6 or 8.

124. The compound of claim 121 wherein:

-

125. The compound of claim 121, selected from the group consisting of: 4-

Methoxy-23,24,25-triazatetracyclo(18.2.1.1^2,5. l^7>10)pentacosa-2(25),3,5,7,9,20,22-heptaene and 4-Methoxy-24,25,26-triazatetracyclo(19.2.1.1²'⁵.l^7,10)hexacosa-2(26),3,5,7,9,21,23- heptaene, or a pharmaceutically acceptable salt thereof.

0

5

126. A composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula (IV):

or a pharmaceutically acceptable salt thereof, wherein:

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃;

R,, and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and p is an integer ranging from 6 to 8; with the proviso that the compound of Formula (IV) is not: cyclononylprodiginine, methylcyclooctylprodiginine, methylcyclodecylprodiginine, ethylcyclononylprodiginine,

R39FF,

R39MF,

R39SF,

61 OFF or

610MF.

127. The composition of claim 126, wherein, in the compound of Formula (TV): R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and p is an integer ranging from 6 to 8; with the proviso that the compound of Formula (IV) is not: cyclononylprodiginine, methylcyclooctylprodiginine, methylcyclodecylprodiginine, ethylcyclononylprodiginine, R39FF, R39MF, R39SF, 61 OFF or 0 610MF.

128. The composition of claim 126, wherein, in the compound of Formula (IN): R₂ is selected from the group consisting of -CH₃; -CH₂CH₃, and -CH₂C₆H₅; ₅ R₆ is -H; p is an integer of 6 and 8.

129. The composition of claim 126, wherein, in the compound of Formula (IN): R₂ is selected from the group consisting of -CH₂CH₃, and -CH₂C₆H₅; „ R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; p is an integer ranging from 6 to 8.

130. The composition of claim 126, wherein the compound of Formula (TV) is selected from the group consisting of: 4-Methoxy-23 ,24,25- 5 triazatetracyclo(l 8.2.1. l^2,s. l^7,10)pentacosa-2(25),3,5,7,9,20,22-heptaene, and 4-Methoxy- 24,25,26-triazatetracyclo(19.2.1.1²'⁵.l^7,10)hexacosa-2(26),3,5,7,9,21,23-heptaene, or a pharmaceutically acceptable salt thereof.

131. A method for treating or preventing a cancer or neoplastic disease _Q comprising administering to a patient in need of such treatment or prevention a composition comprising a therapeutically effective amount of a compound of Formula (IV):

35

IV

or a pharmaceutically acceptable salt thereof, wherein:

10

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR,₀R_nRι₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; . - R,₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R,, and R₁₂ are independently C,-C₃ straight or branched chain alkyl; and p is an integer ranging from 6 to 8.

_π

132. The method of claim 131, wherein the compound of Formula (TV) is ethylcyclononylprodiginine.

133. The method of claim 131, wherein the compound of Formula (IV) is cyclononylprodiginine, methylcycloocytlprodiginine, methylcyclodecylprodiginine, R39FF, R39MF, R39SF, 61 OFF or 61 OMF, or a pharmaceutically acceptable salt thereof.

25

134. The method of claim 131, wherein, in the compound of Formula (IV): R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R_t is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and

3„ p is an integer ranging from 6 to 8.

135. The method of claim 131, wherein, in the compound of Formula (IV): R₂ is selected from the group consisting of -CH₃; -CH₂CH₃, and -CH₂C₆H₅; R₆ is -H;

- - p is an integer of 6 or 8.

136. The method of claim 131, wherein, in the compound of Formula (FV): R₂ is selected from the group consisting of -CH₂CH₃, and -CH₂C₆H₅;

Rg is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; p is an integer ranging from 6 to 8.

137. The method of claim 131, wherein, in the compound of Formula (IV): R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₆ is selected from the group consisting of -H, -CH₃, -CH₂CH₃; and p is an integer ranging from 6 to 8.

10

138. The composition of claim 131, wherein the compound of Formula (IN) is selected from the group consisting of: 4-Methoxy-23, 24,25- triazatetracyclo(18.2.1.1²'⁵.l^7,10)pentacosa-2(25),3,5,7,9,20,22-heptaene and 4-Methoxy- _j 24,25,26-triazatetracyclo(19.2.1.1²'⁵.l⁷'¹⁰)hexacosa-2(26),3,5,7,9,21,23-heptaene, or a pharmaceutically acceptable salt thereof.

139. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising a contacting a cancer cell or neoplastic cell with an effective amount of a

_9f) composition comprising a pharmaceutically acceptable canier and a compound of Formula (IV):

₃„ or a pharmaceutically acceptable salt thereof, wherein:

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃;

35 R,₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R,, and R,₂ are independently C,-C₃ straight or branched chain alkyl; and ^ p is an integer ranging from 6 to 8.

140. The method of claim 139, wherein the compound of Formula (IV) is ethylcyclononylprodiginine.

_{1 n}

141. The method of claim 139, wherein the compound of Formula (TV) is selected from the group consisting of: cyclononylprodiginine, methylcycloocytlprodiginine, methylcyclodecylprodiginine, R39FF, R39MF, R39SF, 610FF and 610MF, or a pharmaceutically acceptable salt thereof.

. _

142. The method of claim 139, wherein, in the compound of Formula (IV):

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H_S; R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and p is an integer ranging from 6 to 8.

143. The method of claim 139, wherein, in the compound of Formula (IV):

20 R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₆ is -H; and p is an integer of 6 or 8.

,

144. The method of claim 139, wherein, in the compound of Formula (TV):

R₂ is selected from the group consisting of -CH₂CH₃, and -CH₂C₆H_S; Rg is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and p is an integer ranging from 6 to 8.

3₀

145. The method of claim 139, wherein, in the compound of Formula (IV) :

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₆ is selected from the group consisting of -H, -CH₃, -CH₂CH₃; and p is an integer ranging from 6 to 8.

35

146. The method of claim 139, wherein the compound of Formula (TV) is selected from the group consisting of: 4-Methoxy-23,24,25- triazatetracyclo(l 8.2.1.1^2,5. l^7,I0)pentacosa-2(25),3,5,7,9,20,22-heptaene and 4-Methoxy- ₅ 24,25,26-triazatetracyclo(19.2.1.1²'⁵.l⁷'^I0)hexacosa-2(26),3,5,7,9,21,23-heptaene or a pharmaceutically acceptable salt thereof.

147. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective

- _ amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (TV), or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (TV):

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR_I0R„R_12J -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and ₁₅ -C(O)OCH₂CCl₃;

R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; R,₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl, and -C₆H₅;

R,, and R,₂ are independently C,-C₃ straight or branched chain alkyl; and _n p is an integer ranging from 6 to 8.

148. The method of claim 147, wherein the compound of Formula (TV) is ethylcyclononylprodiginine.

_<-

149. The method of claim 147, wherein the compound of Formula (IV) is selected from the group consisiting of: cyclononylprodiginine, methylcycloocytlprodiginine, methylcyclodecylprodiginine, R39FF, R39MF, R39SF, 61 OFF and 610MF, or a pharmaceutically acceptable salt thereof.

3„

150. The method of claim 147, wherein, in the compound of Formula (IV):

R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; p is an integer ranging from 6 to 8.

35

151. The method of claim 147, wherein, in the compound of Formula (TV): R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅;

^ p is an integer of 6 or 8.

152. The method of claim 147, wherein, in the compound of Formula (IN): R₂ is selected from the group consisting of -CH₂CH₃, and -CH₂C₆H₅;

Rg is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; _{ι n} p is an integer ranging from 6 to 8.

153. The method of claim 147, wherein, in the compound of Formula (IN) : R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₆ is selected from the group consisting of -H, -CH₃, -CH₂CH₃; and p is an integer ranging from 6 to 8.

15

154. The method of claim 147, wherein the compound of Formula (TV) is selected from the group consisting of: 4-Methoxy-23,24,25- triazatetracyclo( 18.2.1.1^2,s.1⁷'¹⁰)pentacosa-2(25),3 ,5,7,9,20,22-heptaene and 4-Methoxy- 24,25,26-triazatetracyclo(19.2.1.1²'⁵.l⁷'¹⁰)hexacosa-2(26),3,5,7,9,21,23-heptaene, or a

20 pharmaceutically acceptable salt thereof.

155. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of a composition - comprising a pharmaceutically acceptable carrier and a compound having the general Formula (TV):

3 r or a pharmaceutically acceptable salt thereof, wherein: R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR₁₀R„R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

Rg is selected from the group consisting of -H, -CH₃, and -CH₂CH₃;

R_π and R_]2 are independently C,-C₃ straight or branched chain alkyl; and p is an integer ranging from 6 to 8.

156. The method of claim 155, wherein the compound of Formula (IV) is ethylcyclononylprodiginine.

157. The method of claim 155, wherein the compound of Formula (TV) is selected from the group consisiting of: cyclononylprodiginine, methylcycloocytlprodiginine, methylcyclodecylprodiginine, R39FF, R39MF, R39SF, 610FF and 610MF, or a pharmaceutically acceptable salt thereof.

158. The method of claim 155, wherein, in the compound of Formula (TV): R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₆ is selected from the group consisting of -H, -CH₃, and -CH₂CH₃; and p is an integer ranging from 6 to 8.

159. The method of claim 155, wherein, in the compound of Formula (TV): R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; R₆ is -H; and p is an integer of 6 or 8.

160. The method of claim 155, wherein, in the compound of Formula (FV): R₂ is selected from the group consisting of -CH₂CH₃, and -CH₂C₆H₅;

161. The method of claim 155, wherein, in the compound of Formula (TV): R₂ is selected from the group consisting of -CH₃, -CH₂CH₃, and -CH₂C₆H₅; Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃; and p is an integer ranging from 6 to 8.

162. The method of claim 155, wherein the compound of Formula (TV) is selected from the group consisting of: 4-Methoxy-23,24,25- triazatetracyclo(l 8.2.1.1²'⁵. l⁷'¹⁰)pentacosa-2(25),3,5,7,9,20,22-heptaene and 4-Methoxy- _Q 24,25,26-triazatetracyclo(19.2.1.1 '⁵.l^7,I0)hexacosa-2(26),3,5,7,9,21,23-heptaene, or a pharmaceutically acceptable salt thereof.

163. A method for treating or preventing a cancer or neoplastic disease comprising administering to a patient in need of such treatment or prevention a composition , comprising a therapeutically effective amount of a compound of Formula (V):

V

or a pharmaceutically acceptable salt thereof, wherein:

R, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, ₅ -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH₂C₆H₅, -SiR,₀R„R,₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₇ is selected from the group consisting of -H, C,-C,₅ sfraight chain alkyl, _Q -(CH₂)₉CH=CH₂, -(CH₂)₆F, -(CH₂)₅OC₆H₅, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₆H₅, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂)₁₂COOH, -(CH₂)₁₂OH, -(CH₂),₃OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)„COOEt, -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, C₃-C₇ cycloalkyl, -C₆H₅, 2-pynolyl, -3-pynolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, and 3-furanyl, the phenyl being 5 substituted with one or more halo, methyl, methoxyl, hydroxyl, methoxycarbonyl or trifluoromethyl groups;

R₈ is selected from the group consisting of -H, C,-C_n straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, then R^ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then R, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃; _n R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅;

R_n and R,₂ are independently selected from the group consisting of -CH₃, -CH₂CH₃, and -C₃H₇;

R₁₆ is selected from the group consisting of -H, -CH₃, -CH₂CH₂CH₃, and ₁₅ -(CH₂)₆CH₃; and

R₁₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH; with the proviso that the compound of Formula (V) is not: prodigiosin, _n undecylprodigiosin, noφrodigiosin, or nonylprodigiosin.

164. The method of claim 163, wherein the compound of Formula (V) is selected from the group consisting of: 6-methoxy-2-methyl-3-heptylprodigeosene, 4-methoxy-5-((3- methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-2,2'-bi-lH-ρynol, nonylprodigiosin and 3 -heptyl-5 -((3 -methoxy-5 -pynol-2-yl-2H-pynol-2-ylidene)methyl)-2- methyl-4-propyl-pynole, or a pharmaceutically acceptable salt thereof.

-_π

165. The method of claim 163, wherein, in the compound of Formula (V):

R, is -H;

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, -CH(CH₃)₂, and -CH₂C₆H₅;

R₇ is selected from the group consisting of -H, -C,-C₁₅ straight chain alkyl, ₃₅ -(CH₂)₉C=CH₂, -(CH₂)₅CH₂F, -(CH₂)₅OC₅H₆, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₅H₆, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂),₂COOH, -(CH₂),₂OH, -(CH₂),₃OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)„COOEt -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, and 2-pynolyl;

R_g is selected from the group consisting of -H, C--C,, straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R₁₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH; with the proviso that the compound of Formula (V) is not: prodigiosin, undecylprodigiosin, noφrodigiosin, or nonylprodigiosin.

166. The method of claim 163, wherein, in the compound of Formula (V):

R, is -H;

R₇ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₈-C_]5 straight chain alkyl, -(CH₂)₉C=CH₂, -(CH₂)₅CH₂F, -(CH₂)₅OC₅H₆, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₅H₆, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂),₂COOH, -(CH₂),₂OH, -(CH₂),₃OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)„COOEt -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, and 2-pynolyl; Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₆-C_u straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, R, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then R, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃; R,g is selected from the group consisting of -H, -CH₃, -CH₂CH₂CH₃, and -(CH₂)₆CH₃; and

R,₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH; with the proviso that the compound of Formula (V) is not: prodigiosin or undecylprodiginine.

- „

167. A method for inhibiting the growth of a cancer cell or neoplastic cell comprising a contacting a cancer cell or neoplastic cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (V):

20 or a pharmaceutically acceptable salt thereof, wherein:

R- is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl, ₂₅ -CH₂C₆H₅, -SiR₁₀R„R₁₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and -C(O)OCH₂CCl₃;

R₇ is selected from the group consisting of -H, C,-C₁₅ straight chain alkyl, -(CH₂)₉CH=CH₂, -(CH₂)₆F, -(CH₂)₅OC₆H₅, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₆H₅, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂),₂COOH, ₃₀ -(CH₂)₁₂OH, -(CH₂)₁₃OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)„COOEt,

-C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, C₃-C₇ cycloalkyl, -C₆H₅, 2-pynolyl, -3-pynolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, and 3-furanyl, the phenyl being substituted with one or more halo, methyl, methoxyl, hydroxyl, methoxycarbonyl or trifluoromethyl groups;

35 R_g is selected from the group consisting of -H, C,-C,, straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, R₉ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R₁₀ is selected from the group consisting of C,-C₄ sfraight or branched chain alkyl and -C₆H₅; R_u and R₁₂ are independently selected from the group consisting of -CH₃, -CH₂CH₃, and -C₃H₇;

R,₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and ₅ -COOH; with the proviso that the compound of Formula (V) is not: prodigiosin, undecylprodigiosin, noφrodigiosin, or „ nonylprodigiosin.

168. The method of claim 167, wherein the compound of Formula (V) is selected from the group consisting of: 6-methoxy-2-methyl-3-heptylprodigeosene, 4-methoxy-5- ((3-methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-2,2'-bi-lH-pynol, „ nonylprodigiosin and 3-heptyl-5-((3-methoxy-5-pynol-2-yl-2H-pynol-2-ylidene)methyl)-2- methyl-4-ρroρyl-pynole, or a pharmaceutically acceptable salt thereof.

169. The method of claim 167, wherein, in the compound of Formula (V): R, is -H; „ R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl,

-CH(CH₃)₂, and -CH₂C₆H₅;

R₇ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₃-C,₅ straight chain alkyl, -(CH₂)₉CH=CH₂, -(CH₂)₅CH₂F, -(CH₂)₅OC₅H₆, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₅H₆, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, 5 -(CH₂)₁₂COOH, -(CH₂),₂OH, -(CH₂),₃OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)„COOEt -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, and 2-pynolyl;

R_g is selected from the group consisting of -H, C,-C_π straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then R, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃; - „ R₁₆ is selected from the group consisting of -H, -CH₃, -CH₂CH₂CH₃, and

-(CH₂)₆CH₃; and

R₁₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH; with the proviso that the compound of Formula (V) is not: . _- prodigiosin, undecylprodigiosin, noφrodigiosin, or nonylprodigiosin.

170. The method of claim 167, wherein, in the compound of Formula (V):

20

R, is -H;

R₂ is selected from the group consisting of -CH₃, C,-C,₂ straight chain alkyl, -CH(CH₃)₂, and -CH₂C₆H₅;

R₇ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, Cg-C,₅ straight chain ₂₅ alkyl, -(CH₂)₉CH=CH₂, -(CH₂)₅CH₂F, -(CH₂)₅OC₅H₆, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₅H₆, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂)₁₂COOH, -(CH₂)₁₂OH, -(CH₂),₃OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)„COOEt -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)-N(CH₂CH₂)₂O and 2-pynolyl;

R₈ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, Cg-C,, straight chain ₃₀ alkyl, -(CH₂)₄COOEt and -C₆H₅; when R₇ is other than 2-pynolyl, Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃ and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

35 R,₆ is selected from the group consisting of -H, -CH₃, -CH₂CH₂CH₃, and -(CH₂)₆CH₃;

R₁₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH; with the proviso that the compound of Formula (V) is not: prodigiosin or undecylprodiginine.

171. A method for treating or preventing a viral infection in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound of Formula (V):

V

or a pharmaceutically acceptable salt thereof, wherein, in the compound of Formula (V): R, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅,

-C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃;

R₂ is selected from the group consisting of -H, C,-C,₂ straight chain alkyl,

-CH₂C₆H₅, -SiR,₀R„R,₂, -C(O)CH₃, -C(O)C₆H₅, -2-tetrahydropyranyl, -OCH₂OCH₃, and

-C(O)OCH₂CCl₃;

R₇ is selected from the group consisting of -H, C,-C₁₅ straight chain alkyl,

-(CH₂)₉CH=CH₂, -(CH₂)₆F, -(CH₂)₅OC₆H₅, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₆H₅,

-(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂),₂COOH, -(CH₂),₂OH, -(CH₂)₁₃OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)„COOEt,

-C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, C₃-C₇ cycloalkyl, -C₆H₅, 2-pynolyl,

-3-pynolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, and 3-furanyl, the phenyl being substituted with one or more halo, methyl, methoxyl, hydroxyl, methoxycarbonyl or trifluoromethyl groups; R₈ is selected from the group consisting of -H, C,-C,, straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅; - „ R_u and R₁₂ are independently selected from the group consisting of -CH₃, -CH₂CH₃, and -C₃H₇;

R,₆ is selected from the group consisting of -H, -CH₃, -CH₂CH₂CH₃, and -(CH₂)₆CH₃; and

R_I7 is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and ₁₅ -COOH.

172. The method of claim 171, wherein the compound of Formula (V) is selected from the group consisting of: 6-methoxy-2-methyl-3-heptylprodigeosene, 4-methoxy-5-((3- methoxy-5-(lH-pynol-2-yl)-2H-pynol-2-ylidene)methyl)-2,2'-bi-lH-pynol, ₉„ nonylprodigiosin, 3-heptyl-5-((3-methoxy-5-pynol-2-yl-2H-pyrrol-2-ylidene)methyl)-2- methyl-4-propyl-pynole, prodigiosin, undecylprodigiosin, and noφrodigiosin, or a pharmaceutically acceptable salt thereof.

173. The method of claim 171, wherein, in the compound of Formula (V) :

R. is H;

25

R₇ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₃-C,₅ straight chain alkyl, -(CH₂)₉CH=CH₂, -(CH₂)₅CH₂F, -(CH₂)₅OC₅H₆, -(CH₂)₆OH, -(CH₂)₇CN, -₃₀ -CH₂CH₂C₅H₆, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH,

-(CH₂)₁₂COOH, -(CH₂)₁₂OH, -(CHi)₁₃OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)„COOEt -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)-N(CH₂CH₂)₂O, and 2-pynolyl;

R₈ is selected from the group consisting of -H, C,-C,, straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅;

35 when R₇ is other than 2-pynolyl, Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then R, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R,₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH. 0

174. The method of claim 171, wherein, in the compound of Formula (V):

R, is -H;

R₂ is selected from the group consisting of -H, C,-C_I2 straight chain alkyl, -CH(CH₃)₂, and -CH₂C₆H₅; _ς R₇ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₃-C₁₅ straight chain alkyl, -(CH₂)₉CH=CH₂, -(CH₂)₅CH₂F, -(CH₂)₅OC₅H₆, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₅H₆, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂)₁₂COOH, -(CH₂)₁₂OH, -(CH₂)₁₃OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)„COOEt -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)-N(CH₂CH₂)₂O, and 2-pynolyl; _n R₈ is selected from the group consisting of -H, C,-C_u straight chain alkyl,

-(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, ₅ -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R₁₅ is selected from the group consisting of -H, -CH₃, -CH₂CH₂CH₃, and -(CH₂)₆CH₃; and

R₁₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH. 0

5

175. A method for inhibiting the replication or infectivity of a virus comprising a contacting a virus or a virus-infected cell with an effective amount of a composition comprising a pharmaceutically acceptable carrier and a compound having the general Formula (V):

or a pharmaceutically acceptable salt thereof, wherein:

R, is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂C₆H₅, -C(O)OC(CH₃)₃, -C(O)OCH₂C₆H₅, and -C(O)CH₃; 5

R₇ is selected from the group consisting of -H, C,-C,₅ straight chain alkyl, ₀ -(CH₂)₉CH=CH₂, -(CH₂)₆F, -(CH₂)₅OC₆H₅, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₆H₅, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂)₁₂COOH, -(CH₂)₁₂OH, -(CH₂)₁₃OH, -(CH₂)„CN, -(CH₂)„OC(O)NH₂, -(CH₂)„ COOEt, -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)N(CH₂CH₂)₂O, C₃-C₇ cycloalkyl, -C₆H₅, 2-pynolyl, -3-pynolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl, and 3-furanyl, the phenyl being _<- substituted with one or more halo, methyl, methoxyl, hydroxyl, methoxycarbonyl or trifluoromethyl groups;

R_g is selected from the group consisting of -H, C,-C_n straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, Rg is selected from the group consisting of -H, _Q -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R₁₀ is selected from the group consisting of C,-C₄ straight or branched chain alkyl and -C₆H₅; 5 R_u and R,₂ are independently selected from the group consisting of -CH₃, -CH₂CH₃ and -C₃H₇;

R,₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH.

176. The method of claim 175, wherein the compound of Formula (V) is selected „ from the group consisting of: 6-methoxy-2-methyl-3-heptylprodigeosene, 4-methoxy-5-((3- methoxy-5 -(1 H-ρynol-2-yl)-2H-pynol-2-ylidene)methyl)-2,2'-bi- 1 H-pynol, nonylprodigiosin, 3-heptyl-5-((3-methoxy-5-pynol-2-yl-2H-pynol-2-ylidene)methyl)-2- methyl-4-propyl-pynole, prodigiosin, undecylprodigiosin, and noφrodigiosin, or a pharmaceutically acceptable salt thereof. 5

177. The method of claim 175, wherein, in the compound of Formula (V):

R, is -H;

R₂ is selected from the group consisting of -H, C,-C₁₂ straight chain alkyl, -CH(CH₃)₂, and -CH₂C₆H₅; _π R₇ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₃-C₁₅ straight chain alkyl, -(CH₂)₉C=CH₂, -(CH₂)₅CH₂F, -(CH₂)₅OC₅H₆, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₅H₆, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂)₁₂COOH, -(CH₂),₂OH, -(CH₂),₃OH, -(CH₂)„CN, -(CH₂)_uOC(O)NH₂, -(CH₂)„ COOEt, -C(O)(CH₂)₉CH₃, -(CH₂)₅C(O)-N(CH₂CH₂)₂O, and 2-pynolyl; ₂ R₈ is selected from the group consisting of -H, C,-C,, straight chain alkyl,

-(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃, _Q -CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R₁₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -COOH. 5

178. The method of claim 175, wherein, in the compound of Formula (V):

R, is -H;

R₇ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₈-C,₅ straight chain alkyl, -(CH₂)₉C=CH₂, -(CH₂)₅CH₂F, -(CH₂)₅OC₅H₆, -(CH₂)₆OH, -(CH₂)₇CN, -CH₂CH₂C₅H₆, -(CH₂)₄COOH, -(CH₂)₅COOH, -(CH₂)₅COOMe, -(CH₂)„COOH, -(CH₂),₂COOH, - (CH₂)₁₂OH, -(CH₂),₃OH, -(CH₂)_πCN, -(CH₂)„OC(O)NΗ₂, -(CH₂)„COOEt - C(O)(CH₂)₉CH₃, (CH₂)₅C(O)-N(CH₂CH₂)₂O, and 2-pynolyl;

R₈ is selected from the group consisting of -H, -CH₃, -CH₂CH₃, C₆-C_π straight chain alkyl, -(CH₂)₄COOEt, and -C₆H₅; when R₇ is other than 2-pynolyl, Rg is selected from the group consisting of -H, -CH₃, -CH₂CH₃, and -CH₂CH₂CH₃; when R₇ is 2-pynolyl, then Rg is selected from the group consisting of -H, -CH₃,

-CH₂CH₃, -CH₂CH₂CH₃, and -OCH₃;

R₁₇ is selected from the group consisting of -H, -CN, -COOMe, -COOEt, and -^C00H-