WO1999047507A2 - 1,3,4-thiadiazoles useful for the treatment of cmv infections - Google Patents

1,3,4-thiadiazoles useful for the treatment of cmv infections Download PDF

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Publication number
WO1999047507A2
WO1999047507A2 PCT/US1999/003744 US9903744W WO9947507A2 WO 1999047507 A2 WO1999047507 A2 WO 1999047507A2 US 9903744 W US9903744 W US 9903744W WO 9947507 A2 WO9947507 A2 WO 9947507A2
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Prior art keywords
thiadiazol
amino
ammo
benzamide
carboxamide
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WO1999047507A3 (en
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Steven R. Turner
Suvit Thaisrivongs
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Pharmacia and Upjohn Co
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Pharmacia and Upjohn Co
Upjohn Co
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Priority to AU30639/99A priority Critical patent/AU743489B2/en
Priority to CA002320167A priority patent/CA2320167A1/en
Priority to DE69904576T priority patent/DE69904576T2/en
Priority to NZ507032A priority patent/NZ507032A/en
Priority to EP99912221A priority patent/EP1064273B1/en
Priority to DK99912221T priority patent/DK1064273T3/en
Priority to SI9930230T priority patent/SI1064273T1/en
Priority to JP2000536704A priority patent/JP2002506858A/en
Priority to AT99912221T priority patent/ATE229945T1/en
Publication of WO1999047507A2 publication Critical patent/WO1999047507A2/en
Publication of WO1999047507A3 publication Critical patent/WO1999047507A3/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
    • C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • C07D285/135—Nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Definitions

  • the present invention relates to novel 1,3,4-thiadiazole derivatives having useful antiviral activity against herpes virus, cytomegalovirus (CMV).
  • CMV cytomegalovirus
  • the invention also relates to a pharmaceutical composition containing such compounds and methods for the treatment of such viral infections. Many of these compounds are also active against other herpes viruses, such as the varicella zoster virus, the Epstein-Barr virus, the herpes simplex virus, and the human herpes virus type 8 (HHV-8).
  • Derwent Abstracts 46012X/24 discloses anti-inflammatory composition containing 1,3,4-thiadiazoles derivatives as active agents.
  • R j is a) alkyl, b) -(CH 2 ) r C 3 . 7 cycloalkyl, c) -(CH 2 )i-bicycloalkyl, d) -(CH 2 ) r M, e) -(CH 2 ) r W, f) -(CH 2 ) k aryl, wherein aryl may be substituted with one to three R 3 , g) -(CH 2 ) k -het, wherein het may be substituted with one to three R 3 , h) -(CH 2 ) k -Q, wherein Q may be substituted with one to three R 3 , or i) H;
  • W is a) -OR 4 , b) -SR 4 , c) -NHR 6 , or d) -NR ;
  • R 4 is a) C M alkyl, b) C 3 . 7 cycloalkyl, or c) aryl,
  • Rg and R 7 are independently a) C w alkyl, or b) R R 66 aanndd RR 77 ttooggeetthheer with nitrogen form a 4- to 6-membered saturated heterocyclic moiety having one to two atoms selected from the group consisting of oxygen, nitrogen, and sulfur; ⁇ is a) Cm alkyl, b) C 2 . 18 alkenyl, c) C 2 .
  • the compounds of the present invention have antiviral activity against cytomegalovirus (CMV), a member of herpes virus.
  • CMV cytomegalovirus
  • the carbon content of various hydrocarbon containing moieties is indicated by a prefix designating the minimum and maximum number of carbon atoms in the moiety, i.e., the prefix C ⁇ - defines the number of carbon atoms present from the integer "i" to the integer "j", inclusive.
  • C M alkyl refers to alkyl of one to four carbon atoms, inclusive, or methyl, ethyl, propyl, butyl, and isomeric forms such as, for example, straight and branched form thereof.
  • C ⁇ alkyl and “C 1 S alkyl” refer to an alkyl group having one to four, or one to eighteen carbon atoms respectively such as, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl and their isomeric forms thereof.
  • C 2 . 18 alkenyl refers to at least one double bond alkenyl group having two to eighteen carbon atoms, for example, ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, heptdienyl, octenyl, octadienyl, octatrienyl, nonenyl, undecenyl, dodecenyl, etc., and their isomeric forms thereof.
  • C 2 . 18 alkenyl refers to at least one double bond alkenyl group having two to eighteen carbon atoms, for example, ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, heptdienyl, octenyl, octadienyl, octatrienyl, nonenyl, undecenyl,
  • 18 alkynyl refers to at least one triple bond alkynyl group having two to twelve carbon atoms such as, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, octadiynyl, octatriynyl, nonynyl, nonediynyl, etc., and their isomeric forms thereof.
  • C 3 refers to at least one triple bond alkynyl group having two to twelve carbon atoms such as, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, octadiynyl, octatriynyl, nonynyl, nonediynyl
  • cycloalkyl refers to monocyclic hydrocarbons having three to seven carbon atoms such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and their isomeric forms thereof, preferably an cycloalkyl group having three to six carbon atoms.
  • bicycloalkyl refers to saturated alicyclic hydrocarbon systems consisting of two rings only, having two or more atoms in common.
  • C w alkoxy refers to an alkyl group having one to four carbon atoms attached to an oxygen atom of hydroxyl group such as; for example, methoxy, ethoxy, propyloxy, butyloxy, and their isomeric forms thereof.
  • aryl refers to monocarbocyclic or bicarbocyclic aromatic moiety such as; for example phenyl, naphthyl, biphenyl. Each of these moieties may be substituted as appropriate.
  • heterocyclic moiety having one to three atoms selected from the group consisting of oxygen, nitrogen, and sulfur such as, for example, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyranyl, indazolyl, benzothiazolyl, benzoimidazolyl, benzofuryl, isobenzofuryl, benzothiazole, benzoisoxazole, benzothienyl, indolyl, isoindolyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl or cinnolinyl.
  • U refers to 5- to 9-membered unsaturated heterocyclic moiety having one to three atoms selected from the group consisting of oxygen, nitrogen, and sulfur such as, for example, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyranyl, indazolyl, benzothiazolyl, benzoimidazolyl, benzofuryl, isobenzofuryl, benzothiazole, benzoisoxazole, benzothienyl, indolyl, or isoindolyl.
  • the example of Q is 2-, 3-, or 4-piperidinyl, 1-, or 2-pyrrolidinyl, morpholinyl, thiomorpholinyl, dioxolanyl, imidazolidinyl, oxathiolanyl, oxazolidinyl, tetrahydrofuryl, or 2-oxo-l-pyrrolidinyl.
  • halo refers to fluoro, chloro, bromo, or iodo.
  • pharmaceutically acceptable salts refers to those salts which possess the biological effectiveness and properties of the parent compound and which are not biologically or otherwise undesirable.
  • Examples of more preferred compounds of the present invention are: 1. N-(5- ⁇ [3-(cyclohexylamino)propyl]amino ⁇ - l,3,4-thiadiazol-2-yl)-2-ethoxy- 1- naphthamide,
  • the compounds of the present invention and pharmaceutically acceptable salts thereof are useful as antiviral agents.
  • these compounds are useful to combat viral infections in animals, including man.
  • these compounds have anti-viral activity against the herpes virus, cytomegalovirus (CMV).
  • CMV cytomegalovirus
  • Many of these compounds are also active against other herpes viruses, such as the varicella zoster virus, the Epstein-Barr virus, the herpes simplex virus, and the human herpes virus type 8 (HHV-8).
  • the compounds of the present invention are tested in an polymerase assay to show activity described below, which is indicative of a compound's activity and thus of its use as an anti-viral agent.
  • HCMV polymerase assay is performed using a scintillation proximity assay (SPA) as described in several references, such as N.D. Cook, et al.,
  • SPA scintillation proximity assay
  • HCMV is diluted in enzyme dilution buffer containing 50% glycerol, 250 mM NaCl, 10 mM HEPES (pH 7.5), 100 ⁇ g/ml BSA, and 0.01% sodium azide.
  • the HCMV polymerase which is expressed in recombinant baculovirus-infected SF-9 cells and purified according to literature procedures, is added at 10% (or 10 ⁇ l) of the final reaction volume, i.e., 100 ⁇ l.
  • Compounds are diluted in 50% DMSO and 10 ⁇ l are added to each well. Control wells contain an equivalent concentration of DMSO.
  • reactions are initiated via the addition of 6 nM biotinylated poly(dA)-oligo(dT) template/primer to reaction mixtures containing the enzyme, substrate, and compounds of interest. Plates are incubated in a 25°C or 37°C H 2 O bath and te ⁇ ninated via the addition of 40 ⁇ l/reaction of 0.5 M EDTA (pH 8) per well. Reactions are terminated within the time-frame during which substrate incorporation is linear and varied depending upon the enzyme and conditions used, i.e., 30 min. for HCMV polymerase. Ten ⁇ l of streptavidin-SPA beads (20 mg ml in PBS/10% glycerol) are added following termination of the reaction. Plates are incubated 10 min. at 37°C, then equilibrated to room temperature, and counted on a Packard Topcount. Results of the testing of compounds of the present invention in this assay are shown in TABLE 1 below.
  • compositions containing the compound in combination with a suitable excipient are prepared by methods and contain excipients which are well known in the art. A generally recognized compendium of such methods and ingredients is Remington's Pharmaceutical Sciences by E.W. Martin (Mark Publ. Co., 15th Ed., 1975), which is hereby incorporated by reference herein.
  • the quantity of active component that is the compounds of formula I according to this invention, in the pharmaceutical composition and unit dosage form thereof may be varied or adjusted widely depending upon the particular application method, the potency of the particular compound and the desired concentration. Generally, the quantity of active component will range between 0.5% to 90% by weight of the composition.
  • the compounds of the present invention are administered parenterally (for example, by intravenous, intraperitoneal or intramuscular injection), topically, orally, or rectally, depending on whether the preparation is used to treat internal or external viral infections.
  • compositions are administered orally or parenterally at dose levels, calculated as the free base, of about 0.1 to 300 mg/kg, preferably 1.0 to 30 mg/kg of mammal body weight, and are used in man in a unit dosage form, administered one to four times daily in the amount of 1 to 1000 mg per unit dose.
  • the compounds are presented in aqueous solution in a concentration of from about 0.1 to 10%, more preferably about 0.1 to 7%.
  • the solution may contain other ingredients, such as emuls ⁇ iers, antioxidants or buffers.
  • Y is -NHR 1? or _N , R lf Rx and X are as defined previously.
  • 2-Amino-5-bromo- 1,3,4-thiadiazole 2 is prepared through bromination of commercially available 2-amino- 1,3,4-thiadiazole.
  • Compound 3 is prepared through direct bromide displacement of thiadiazole 2 with an appropriate amine.
  • Compound 3 then react with an appropriate acid chloride to provide compound 4.
  • the precipitated solid is isolated by filtration and washed well with water, then dissolved in 300 ml of water containing 40 ml concentrated. HC1. The solution is filtered from a small amount of solid, then 87 g of K 2 HPO 4 in a small quantity of water is added. The resulting slurry is chilled in ice and filtered, and the solid washed well with water. Recrystallization of the product from 400 ml of ethanol provides 26.3 g of the title compound.
  • a mixture of 5-bromo-l,3,4-thiadiazol-2-ylamine (720 mg), (780 mg), and cycloheptylamine (0.51 mg) in 5 ml of DMF is stirred at 60 °C for 4 hours, then diluted with pyridine and centrifuged to remove solids. To one-half of this solution, cooled to 0 °C, is added a solution of 469 mg of 2-ethoxy-l-naphthoyl chloride in 5 ml of chloroform. The solution is stirred at room temperature overnight, then concentrated under reduced pressure.
  • a mixture 5-bromo-l,3,4-thiadiazol-2-ylamine (720 mg), KJHPO ⁇ (780 mg), and 2,2-diphenylethylamine (789 mg) in 5 ml of DMF is stirred at 60 °C for 4 hours, then diluted with pyridine and centrifuged to remove solids. To one-half of this solution, cooled to 0 °C, is added a solution of 2-ethoxy-l-naphthoyl chloride (469 mg) in 5 ml of chloroform. The solution is stirred at room temperature overnight, then concentrated under reduced pressure and diluted with 100 ml of water. The resultant solid is filtered, washed with water, and dried under vacuum to provide 947 mg of the title compound.
  • a mixture of 5-bromo-l,3,4-thiadiazol-2-ylamine (720 mg), K j HPO,, (780 mg), and tryptamine (641 mg) in 5 ml of DMF is stirred at 60 °C for 12 hours, then diluted with pyridine and centrifuged to remove solids. To one-half of this solution, cooled to 0 °C, is added a solution of 469 mg of 2-ethoxy-l-naphthoyl chloride in 5 ml of chloroform. The solution is stirred at room temperature overnight, then concentrated under reduced pressure and diluted with 100 ml of water. The resultant solid is filtered, washed with water, and dried under vacuum to provide 866 mg of white solid.
  • K ⁇ P0 4 (272 mg) and 1.3 mmol of the following amines respectively: phenethylamine, 2-n ⁇ rylmethylamine, l-(3-aminopropyl)-2-pyrrolidinone, 2-pyridmylmethylamine, N-(2-ammoethyl)-N-phenylamine, 2-(lH-mdol-3-yl)ethylamine, ( ⁇ oheptylamine, cyclohexylmethylamine, ( lS,2R,5S)-6,6-dimethylbicyclo[3.1.
  • the resultant 48 mixtures are heated at 60 °C for 3 hours to provide a DMF solutions of the corresponding substituted aminothiadiazole intermediates.
  • the solutions of intermediate aminothiadiazoles are diluted with pyridine to a volume of 10.0 ml, and solids are removed by centrifugation.
  • the supernatants are aliquoted into wells of 96-well plates (0.40 ml per well) respectively, and to each well is added 0.26 ml of a 0.2 M chloroform solution of the following acid chlorides respectively:
  • MS refers to mass spectral data
  • % inhib refers to percentage of inhibition at 25 uM concentration in CMV polymerase assay.

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Abstract

The present invention presents novel 1,3,4-thiadiazole derivatives of formula (I) which have useful antiviral activity against herpes virus, cytomegalovirus (CMV).

Description

1,3,4-THIADIAZOLES USEFUL FOR THE TREATMENT OF CMV INFECTIONS
BACKGROUND OF THE INVENTION The present invention relates to novel 1,3,4-thiadiazole derivatives having useful antiviral activity against herpes virus, cytomegalovirus (CMV). The invention also relates to a pharmaceutical composition containing such compounds and methods for the treatment of such viral infections. Many of these compounds are also active against other herpes viruses, such as the varicella zoster virus, the Epstein-Barr virus, the herpes simplex virus, and the human herpes virus type 8 (HHV-8).
INFORMATION DISCLOSURE Derwent Abstracts 07484C/05 discloses 2-acylamino- 1,3,4-thiadiazole derivatives useful as pesticides, optical brightening agents, and intermediates for pharmaceuticals.
Derwent Abstracts 46012X/24 discloses anti-inflammatory composition containing 1,3,4-thiadiazoles derivatives as active agents.
J. Chem. Soc. (C), Vol. 13, 1813-1823, (1970) describes addition-cyclisation reactions undergone by aroyl isothiocyanates with NN-diaminoguanidines. J. Heterocyclic Chem. Vol. 25, 1071-1074 describes a new route to 1,2,4- triazoles and 1,3,4-thiadiazoles from 1-acylbithiourea.
SUMMARY OF THE INVENTION The present invention provides a compound of formula I
Figure imgf000003_0001
I or pharmaceutically acceptable salts thereof wherein: Y is a) -NHR1? or
Figure imgf000003_0002
X is -O-, -S(=O)h-, -CH2-, or -NRg-; Rj is a)
Figure imgf000004_0001
alkyl, b) -(CH2)rC3.7 cycloalkyl, c) -(CH2)i-bicycloalkyl, d) -(CH2)rM, e) -(CH2)rW, f) -(CH2)k aryl, wherein aryl may be substituted with one to three R3, g) -(CH2)k-het, wherein het may be substituted with one to three R3, h) -(CH2)k-Q, wherein Q may be substituted with one to three R3, or i) H;
Ra is a) H, b) CM alkyl, c) -C(=O)Cw alkyl, d) -S(=O)Cw alkyl, e) -CO2Cw alkyl, or f) -CO2CH2phenyl; Ra is a) halo, b) CM alkyl, c) C1 alkoxy, d) benzyl, e) -CN, ) -SO2F, g) -SO2NH2, h) -CF„ i) -NO2) j) -OCH2O-, k) -CO2(CM alkyl), 1) -C(-O)CM alkyl, m) -C(=O)NH2, n) -NHCO2(C^ alkyl), or o) -C(=O)-O-C(=O)-; M is a) -CN b) halo, c) -CO2Cw alkyl, d) -CH(phenyl)2,
Figure imgf000005_0001
W is a) -OR4, b) -SR4, c) -NHR6, or d) -NR ;
R4 is a) CM alkyl, b) C3.7 cycloalkyl, or c) aryl,
R5 is a) CM alkyl, b) C3.7 cycloalkyl, c) aryl, or d) -C(=O)CM alkyl;
Rg and R7 are independently a) Cw alkyl, or b) R R66 aanndd RR77 ttooggeetthheer with nitrogen form a 4- to 6-membered saturated heterocyclic moiety having one to two atoms selected from the group consisting of oxygen, nitrogen, and sulfur; ^ is a) Cm alkyl, b) C2.18 alkenyl, c) C2.18 alkynyl, d) C2.g alkyl substituted with one to three halo,
Figure imgf000005_0002
alkoxy, -OH, -SH, or -CO2H, e) C2^ alkenyl substituted with aryl, wherein the aryl may be in turn substituted with one to three Ra, f) -(CHa aryl, wherein aryl may be substituted with one to three R3, g) -(CH2)rQ, wherein het may be substituted with one to three R3, or h) -(CH2)i-U, wherein Q may be substituted with one to three R3; aryl is phenyl or naphthyl; het is 5- to 10-membered unsaturated heterocyclic moiety having one to three atoms selected from the group consisting of oxygen, nitrogen, and sulfur; U is 5- to 9-membered unsaturated heterocyclic moiety having one to three atoms selected from the group consisting of oxygen, nitrogen, and sulfur;
Q is 5- or 6-membered saturated heterocyclic moiety having one to two atoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein nitrogen atom may be in turn substituted with C1 alkyl, phenyl, benzyl, -C(=O)CM alkyl, or - CO2Cw alkyl; h is 0, 1, or 2; i is 0, 1, 2, 3, or 4; j is 2, 3, or 4; k is 0, 1, 2, 3, 4, 5, or 6; and with the following provisos: a)where R3 is phenyl or 4-methoxyphenyl, Rx is other than phenyl,
4-methoxyphenyl, or 4-chlorophenyl; b)where R3 is -CH2phenyl, Rx is other than phenyl or -CH2phenyl; c)where R3 is H, substituted or unsubstituted alkyl or phenyl, Rx is other than unsubstituted alkyl or phenyl.
The compounds of the present invention have antiviral activity against cytomegalovirus (CMV), a member of herpes virus.
DETAILED DESCRIPTION OF THE INVENTION For the purpose of the present invention, the carbon content of various hydrocarbon containing moieties is indicated by a prefix designating the minimum and maximum number of carbon atoms in the moiety, i.e., the prefix C^- defines the number of carbon atoms present from the integer "i" to the integer "j", inclusive.
Thus, CM alkyl refers to alkyl of one to four carbon atoms, inclusive, or methyl, ethyl, propyl, butyl, and isomeric forms such as, for example, straight and branched form thereof.
The terms "C^ alkyl", and "C1 S alkyl" refer to an alkyl group having one to four, or one to eighteen carbon atoms respectively such as, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl and their isomeric forms thereof.
The terms "C2.18 alkenyl" refers to at least one double bond alkenyl group having two to eighteen carbon atoms, for example, ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, heptdienyl, octenyl, octadienyl, octatrienyl, nonenyl, undecenyl, dodecenyl, etc., and their isomeric forms thereof. The term "C2.18 alkynyl" refers to at least one triple bond alkynyl group having two to twelve carbon atoms such as, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, octadiynyl, octatriynyl, nonynyl, nonediynyl, etc., and their isomeric forms thereof. The term "C3.7 cycloalkyl" refers to monocyclic hydrocarbons having three to seven carbon atoms such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and their isomeric forms thereof, preferably an cycloalkyl group having three to six carbon atoms.
The term "bicycloalkyl" refers to saturated alicyclic hydrocarbon systems consisting of two rings only, having two or more atoms in common.
The terms "Cw alkoxy" refers to an alkyl group having one to four carbon atoms attached to an oxygen atom of hydroxyl group such as; for example, methoxy, ethoxy, propyloxy, butyloxy, and their isomeric forms thereof.
The term "aryl" refers to monocarbocyclic or bicarbocyclic aromatic moiety such as; for example phenyl, naphthyl, biphenyl. Each of these moieties may be substituted as appropriate. Aryl is preferably phenyl or phenyl substituted with Cw alkyl, CM alkoxy, halo, -CN, -SO2NH2, -SO2F-, -NO2, -C(=O)-O-C(=O)- or -OCHjjO-.
The term "het" refers to a 5- to 10-membered unsaturated heterocyclic moiety having one to three atoms selected from the group consisting of oxygen, nitrogen, and sulfur such as, for example, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyranyl, indazolyl, benzothiazolyl, benzoimidazolyl, benzofuryl, isobenzofuryl, benzothiazole, benzoisoxazole, benzothienyl, indolyl, isoindolyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl or cinnolinyl.
The term "U" refers to 5- to 9-membered unsaturated heterocyclic moiety having one to three atoms selected from the group consisting of oxygen, nitrogen, and sulfur such as, for example, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyranyl, indazolyl, benzothiazolyl, benzoimidazolyl, benzofuryl, isobenzofuryl, benzothiazole, benzoisoxazole, benzothienyl, indolyl, or isoindolyl.
The term "Q" refers to 5- or 6-membered saturated heterocyclic moiety having one to two atoms selected from the group consisting of oxygen, nitrogen, and sulfur, wherein nitrogen atom may be in turn substituted with C^ alkyl, phenyl, benzyl, or -C(=O)C!^ alkyl. The example of Q is 2-, 3-, or 4-piperidinyl, 1-, or 2-pyrrolidinyl, morpholinyl, thiomorpholinyl, dioxolanyl, imidazolidinyl, oxathiolanyl, oxazolidinyl, tetrahydrofuryl, or 2-oxo-l-pyrrolidinyl.
The term "halo" refers to fluoro, chloro, bromo, or iodo.
The term "pharmaceutically acceptable salts" refers to those salts which possess the biological effectiveness and properties of the parent compound and which are not biologically or otherwise undesirable.
Throughout this application, abbreviations which are well known to one of ordinary skill in the art may be used, such as "Ph" for phenyl, "Me" for methyl, etc.
Examples of preferred compounds of the present invention are:
1. N-(5-{[3-(cyclohexylamino)propyl]amino}- l,3,4-thiadiazol-2-yl)-2-ethoxy- 1- naphthamide,
2. N-(5-{[3-(cyclohexylamino)propyl]amino}-l,3,4-thiadiazol-2-yl)-l,3-dioxo-l,3- dihydro-2-benzofuran-5-carboxamide,
3. N-{5-[(3,3-diphenylpropyl)amino]-l,3,4-thiadiazol-2-yl}-l,3-dioxo-l,3-dihydro-2- benzofuran-5-carboxamide, 4. N-{5-[(2,2-diphenylethyl)amino]-l,3,4-thiadiazol-2-yl}-l,3-dioxo-l,3-dihydro-2- benzofuran-5-carboxamide,
5. l,3-dioxo-N-[5-(undecylamino)- l,3,4-thiadiazol-2-yl]- l,3-dihydro-2-benzofuran- 5-carboxamide,
6. N-[5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept-2-yl]methyl}amino)-l,3,4-thiadiazol- 2-yl]- 1,3-dioxo- l,3-dihydro-2-benzofuran-5-carboxamide,
7. l,3-dioxo-N-{5-[(4-phenylbutyl)amino]- l,3,4-thiadiazol-2-yl}- l,3-dihydro-2- benzofuran-5-carboxamide,
8. N-(5-{[2-(lH-indol-3-yl)ethyl]amino}-l,3,4-thiadiazol-2-yl)-l,3-dioxo-l,3- dihydro-2-benzofuran-5-carboxamide, 9. (E)-N-(5-{[3-(cyclohexylamino)propyl]amino}- l,3,4-thiadiazol-2-yl)-9- octadecenamide,
10. 2-ethoxy-N-(5-{[2-(lH-indol-3-yl)ethyl]amino}-l,3,4-thiadiazol-2-yl)-l- naphthamide,
11. 2,6-dichloro-N-(5-{[3-(cyclohexylamino)propyl]amino}-l,3,4-thiadiazol-2- yl)benzamide,
12. N-[5-(cycloheptylamino)- l,3,4-thiadiazol-2-yl]-2-ethoxy- 1-naphthamide,
13. N-[5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept-2-yl]methyl}amino)-l,3,4-thiadiazol- 2-yl]-2-ethoxy- 1-naphthamide,
14. (E)-N-(5-{[4-(aminosulfonyl)benzyl]amino}-l,3,4-thiadiazol-2-yl)-9- octadecenamide,
15. N-{5-[(2,2-diphenylethyl)amino]- l,3,4-thiadiazol-2-yl}-2-ethoxy- 1-naphthamide, 16. (E)-N-(5-{[3-(cyclohexylamino)propyl]amino}-l,3,4-thiadiazol-2-yl)-3-phenyl-2- propenamide,
17. 2,6-dichloro-N-{5-[(3,3-diphenylpropyl)amino]-l,3,4-thiadiazol-2-yl}benzamide,
18. 2,6-dichloro-N-{5-t(2,2-diphenylethyl)amino]-l,3,4-thiadiazol-2-yl}benzamide, 19. (E)-N-{6-[( l,3-benzodioxol-5-ylmethyl)amino]- l,3,4-thiadiazol-2-yl}-9- octadecenamide,
20. N-(5-{[4-(aminosulfonyl)benzyl]amino}-l,3,4-thiadiazol-2-yl)-2,6- dichlorobenzamide,
21. 2,6-dichloro-N-(5-{[2-( lH-indol-3-yl)ethyl]amino}- l,3,4-thiadiazol-2- yl)benzamide,
22. 4-cyano-N-{5-[(2,2-diphenylethyl)amino]-l,3,4-thiadiazol-2-yl}benzamide,
23. N-{5-[(l,3-benzodioxol-5-ylmethyl)amino]-l,3,4-thiadiazol-2-yl}-l,3-dioxo-l,3- dihydro-2-benzofuran-5-carboxamide,
24. 4-cyano-N-(5-{[3-(cyclohexylamino)propyl]amino}-l,3,4-thiadiazol-2- yl)benzamide,
25. N-(5-{[2-( lH-indol-3-yl)ethyl]amino}- l,3,4-thiadiazol-2-yl)-5-nitro-2-furamide,
26. 2,6-dichloro-N-[5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept-2-yl]methyl}amino)- 1,3 ,4-thiadiazol-2-yl]benzamide,
27. 4-cyano-N-(5-{[2-(lH-indol-3-yl)ethyl]amino}-l,3,4-thiadiazol-2-yl)benzamide, 28 N-[5-(cycloheptylamino)- l,3,4-thiadiazol-2-yl]- 1,3-dioxo- l,3-dihydro-2- benzofuran-5-carboxamide,
29. N-{5-[(l,3-benzodioxol-5-ylmethyl)amino]-l,3,4-thiadiazol-2-yl}-2,6- dichlorobenzamide,
30. N-{5-[(2,2-diphenylethyl)amino]-l,3,4-thiadiazol-2-yl}-2-methoxybenzamide, 31. (E)-N-(5-{[4-(aminosulfonyl)benzyl]amino}- l,3,4-thiadiazol-2-yl)-3-phenyl-2- propenamide,
32. (E)-N-[5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept-2-yl]methyl}amino)- 1,3,4- thiadiazol-2-yl]-9-octadecenamide,
33. (E)-N-(5-{[2-(lH-indol-3-yl)ethyl]amino}-l,3,4-thiadiazol-2-yl)-9- octadecenamide,
34. (E)-N-[5-(cycloheptylamino)-l,3,4-thiadiazol-2-yl]-9-octadecenamide,
35. (E)-N-{5-[(4-fluorobenzyl)amino]-l,3,4-thiadiazol-2-yl}-9-octadecenamide,
36. 2,6-dichloro-N-{5-[(4-phenylbutyl)amino]- l,3,4-thiadiazol-2-yl}benzamide, or
37. N-(5-{[4-(aminosulfonyl)benzyl]amino}-l,3,4-thiadiazol-2-yl)-2-ethoxy-l- naphthamide.
Examples of more preferred compounds of the present invention are: 1. N-(5-{[3-(cyclohexylamino)propyl]amino}- l,3,4-thiadiazol-2-yl)-2-ethoxy- 1- naphthamide,
2. N-(5-{[3-(cyclohexylamino)propyl]amino}-l,3,4-thiadiazol-2-yl)-l,3-dioxo-l,3- dihydro-2-benzofuran-5-carboxamide, 3. N-{5-[(3,3-diphenylpropyl)amino]- l,3,4-thiadiazol-2-yl}- 1,3-dioxo- l,3-dihydro-2- benzofuran-5-carboxamide,
4. N-{5-[(2,2-diphenylethyl)amino]- l,3,4-thiadiazol-2-yl}- 1,3-dioxo- l,3-dihydro-2- benzofuran-5-carboxamide,
5. l,3-dioxo-N-[5-(undecylamino)- l,3,4-thiadiazol-2-yl]- l,3-dihydro-2-benzofuran- 5-carboxamide,
6. N-t5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept-2-yl]methyl}amino)- 1,3,4-thiadiazol- 2-yl]- 1,3-dioxo- l,3-dihydro-2-benzofuran-5-carboxamide,
7. l,3-dioxo-N-{5-[(4-phenylbutyl)amino]- l,3,4-thiadiazol-2-yl}- l,3-dihydro-2- benzofuran-5-carboxamide, 8. N-(5-{[2-( lH-indol-3-yl)ethyl]amino}- l,3,4-thiadiazol-2-yl)- 1,3-dioxo- 1,3- dihydro-2-benzofuran-5-carboxamide, or 9. (E)-N-(5-{[3-(cyclohexylamino)propyl]amino}-l,3,4-thiadiazol-2-yl)-9- octadecenamide.
The compounds of the present invention and pharmaceutically acceptable salts thereof are useful as antiviral agents. Thus, these compounds are useful to combat viral infections in animals, including man. Specifically, these compounds have anti-viral activity against the herpes virus, cytomegalovirus (CMV). Many of these compounds are also active against other herpes viruses, such as the varicella zoster virus, the Epstein-Barr virus, the herpes simplex virus, and the human herpes virus type 8 (HHV-8).
Also, while many of the compounds of the present invention have shown activity against the CMV polymerase, these compounds may be active against the cytomegalovirus by this or other mechanisms of action. Thus, the description below of these compounds' activity against the CMV polymerase is not meant to limit the present invention to a specific mechanism of action.
The compounds of the present invention are tested in an polymerase assay to show activity described below, which is indicative of a compound's activity and thus of its use as an anti-viral agent.
The HCMV polymerase assay is performed using a scintillation proximity assay (SPA) as described in several references, such as N.D. Cook, et al.,
Pharmaceutical Manufacturing International, pages 49-53 (1992); K. Takeuchi, Laboratory Practice, September issue (1992); US Patent No. 4,568,649 (1986); which are incorporated by reference herein. Reactions are performed in 96-well plates. The assay is conducted in 100 μl volume with 5.4 mM HEPES (pH 7.5), 11.7 mM KC1, 4.5 mM MgCl2, 0.36 mg ml BSA, and 90 nM 3H-dTTP. Assays are run with and without CHAPS, (3-[(3-Cholamidopropyl)-dimethylammonio]-l-propane- sulfonate) at a final concentration of 2 mM. HCMV is diluted in enzyme dilution buffer containing 50% glycerol, 250 mM NaCl, 10 mM HEPES (pH 7.5), 100 μg/ml BSA, and 0.01% sodium azide. The HCMV polymerase, which is expressed in recombinant baculovirus-infected SF-9 cells and purified according to literature procedures, is added at 10% (or 10 μl) of the final reaction volume, i.e., 100 μl. Compounds are diluted in 50% DMSO and 10 μl are added to each well. Control wells contain an equivalent concentration of DMSO. Unless noted otherwise, reactions are initiated via the addition of 6 nM biotinylated poly(dA)-oligo(dT) template/primer to reaction mixtures containing the enzyme, substrate, and compounds of interest. Plates are incubated in a 25°C or 37°C H2O bath and teπninated via the addition of 40 μl/reaction of 0.5 M EDTA (pH 8) per well. Reactions are terminated within the time-frame during which substrate incorporation is linear and varied depending upon the enzyme and conditions used, i.e., 30 min. for HCMV polymerase. Ten μl of streptavidin-SPA beads (20 mg ml in PBS/10% glycerol) are added following termination of the reaction. Plates are incubated 10 min. at 37°C, then equilibrated to room temperature, and counted on a Packard Topcount. Results of the testing of compounds of the present invention in this assay are shown in TABLE 1 below.
These compounds of the present invention are administered in a pharmaceutical composition containing the compound in combination with a suitable excipient, the composition being useful in combating viral infections. Pharmaceutical compositions containing a compound appropriate for antiviral use are prepared by methods and contain excipients which are well known in the art. A generally recognized compendium of such methods and ingredients is Remington's Pharmaceutical Sciences by E.W. Martin (Mark Publ. Co., 15th Ed., 1975), which is hereby incorporated by reference herein.
The quantity of active component, that is the compounds of formula I according to this invention, in the pharmaceutical composition and unit dosage form thereof may be varied or adjusted widely depending upon the particular application method, the potency of the particular compound and the desired concentration. Generally, the quantity of active component will range between 0.5% to 90% by weight of the composition.
The compounds of the present invention are administered parenterally (for example, by intravenous, intraperitoneal or intramuscular injection), topically, orally, or rectally, depending on whether the preparation is used to treat internal or external viral infections.
For internal infections, the compositions are administered orally or parenterally at dose levels, calculated as the free base, of about 0.1 to 300 mg/kg, preferably 1.0 to 30 mg/kg of mammal body weight, and are used in man in a unit dosage form, administered one to four times daily in the amount of 1 to 1000 mg per unit dose.
For parenteral administration or for administration as drops, as for eye infections, the compounds are presented in aqueous solution in a concentration of from about 0.1 to 10%, more preferably about 0.1 to 7%. The solution may contain other ingredients, such as emulsϋiers, antioxidants or buffers. The exact regimen for administration of the compounds and compositions disclosed herein will necessarily be dependent upon the needs of the individual subject being treated, the type of treatment and, of course, the judgment of the attending practitioner.
The following Scheme outlines the preparation of the compounds of the present invention.
SCHEME I
Figure imgf000012_0001
Figure imgf000012_0002
4 3
In Scheme I, Y is -NHR1? or _N , Rlf Rx and X are as defined previously. The synthesis of structures 3 and 4, the compounds of the present invention, required two or three steps. 2-Amino-5-bromo- 1,3,4-thiadiazole 2 is prepared through bromination of commercially available 2-amino- 1,3,4-thiadiazole. Compound 3 is prepared through direct bromide displacement of thiadiazole 2 with an appropriate amine. Compound 3 then react with an appropriate acid chloride to provide compound 4.
It will be apparent to those skilled in the art that the described synthetic procedures are merely representative in nature and that alternative synthetic processes are known to one of ordinary skill in organic chemistry.
The compounds and their preparations of the present invention will be better understood in connection with the following examples, which are intended as an illustration of and not a limitation upon the scope of the invention.
EXAMPLE 1 Preparation of starting material 5-bromo-l,3,4-thiadiazol-2- ylamine. To a stirred solution of 2-amino- 1,3,4-thiadiazole (40.5 g) in 250 ml of acetic acid is added 22.7 ml of bromine over about 20 minutes. The flask is surrounded by an ice bath during the addition to maintain the reaction temperature near 25 °C. Following the addition, the ice bath is removed and the clear red solution stirred at ambient temperature for 18 hours, then added to IL of cracked ice. Excess bromine is quenched with NaHSO3, and 40 ml of 50% aqueous NaOH is added. The precipitated solid is isolated by filtration and washed well with water, then dissolved in 300 ml of water containing 40 ml concentrated. HC1. The solution is filtered from a small amount of solid, then 87 g of K2HPO4 in a small quantity of water is added. The resulting slurry is chilled in ice and filtered, and the solid washed well with water. Recrystallization of the product from 400 ml of ethanol provides 26.3 g of the title compound.
NMR (DMSO-d6) δ 7.51 ppm.
EXAMPLE 2 Preparation of tert-Butyl 4-(5-amino-l,3,4-thiadiazol-2-yl)tetrahydro- l(2H)-pyrazinecarboxylate.
Figure imgf000013_0001
A mixture of 5-bromo-l,3,4-thiadiazol-2-ylamine (9.27 g), Boc-piperazine (11.51 g), and KjHPO4 (13.4 g) in 30 ml of DMF is heated at 100 °C under argon for four hours, then cooled and added to 100 g of ice. The mixture is extracted with ethyl acetate, and the organic phase washed twice with water and dried (MgSO4). Following removal of the solvent under reduced pressure, the residue is flash chromatographed on silica using 4% methanol in dichloromethane to afford 8.32 g of the title compound as a solid. Recrystallization from 240 ml of 1:1 acetonitrile- toluene provides 6.65 g of solid. XNMR δ 1.47, 3.34, 3.53, 4.8 ppm
IR 3411, 3132, 1698, 1676, 1500, 1427, 1251, 1167 cm 1 El HRMS m/z found: 285.1277 M.p. 215-216 °C.
EXAMPLE 3 Preparation of N-(5-Amino-l,3,4-thiadiazol-2-yl)-N-phenethylamine.
Figure imgf000014_0001
A mixture of 5-bromo-l,3,4-thiadiazol-2-ylamine (360 mg), phenethylamine (0.38 ml), and KjHPO4 (522 mg) in 2 ml of DMF is heated under nitrogen at 100 °C for two hours, then partitioned between water and ethyl acetate. The organic phase is washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. Flash chromatography of the residue on silica using 4-5% methanol in dichloromethane provides 261 mg of the title compound. Recrystallization of 238 mg of this from 10 ml of 1: 1 acetonitrile toluene affords 205 mg of crystals. Η NMR δ 2.92, 3.50, 7.2-7.3 ppm IR 3186, 1565, 1505 cm"1 El MS m/z 221 M.p. 156-157 °C Anal. Found: C, 54.51; H, 5.47; N, 25.26; S, 14.30.
EXAMPLE 4 Preparation of 5-Morpholino-l,3,4-thiadiazol-2-ylamine.
Figure imgf000014_0002
A mixture of 5-bromo-l,3,4-thiadiazol-2-ylamine, K2HPO4 (5.7 g), and 5.3 ml of morpholine in 20 ml of DMF is heated at 80 °C under nitrogen for 18 hours, then diluted with 50 ml of water. The clear solution is placed in a continuous extractor and extracted with a brisk flow of dichloromethane for 18 hours. The solution is dried over MgSO4 and concentrated under reduced pressure, with toluene azeotropes to remove DMF. Recrystallization of the residual solid from 50 ml of acetonitrile and 100 ml of toluene affords 3.92 g of the title compound. Η NMR δ 3.34, 3.80 ppm
LR 1528, 1499, 1448, 1245, 1112, 1036, 906 cm 1
El MS m/z 186
Anal. Found: C, 38.67; H, 5.48; N, 30.17; S, 17.18.
EXAMPLE 5 Preparation of tert-Butyl N-{2-[(5-amino-l,3,4-thiadiazol-2- yl)amino]ethyl}carbamate.
Figure imgf000015_0001
A mixture of 5-bromo-l,3,4-thiadiazol-2-ylamine (5.40 g), KgHPO 4 (7.84 g), and Boc-ethylenediamine (9.6 g) in 20 ml of DMF is stirred at ambient temperature for 18 hours. The solid paste obtained is recrystallized from 100 ml of acetonitrile and 100 ml of water to provide 6.18 g (79%) of the title compound.
Η NMR (MeOH-d4) δ 1.40, 3.2-3.3 ppm
LR 2989, 1676, 1577, 1512, 1366 cm 1
El MS m/z 260 M.p. 219-220 °C.
EXAMPLE 6 Preparation of N-t5-(Cycloheptylamino)-l,3,4-thiadiazol-2-yl]-2-ethoxy- l-naphthamide.-ethoxy-1-naphthoyl).
Figure imgf000015_0002
A mixture of 5-bromo-l,3,4-thiadiazol-2-ylamine (720 mg),
Figure imgf000015_0003
(780 mg), and cycloheptylamine (0.51 mg) in 5 ml of DMF is stirred at 60 °C for 4 hours, then diluted with pyridine and centrifuged to remove solids. To one-half of this solution, cooled to 0 °C, is added a solution of 469 mg of 2-ethoxy-l-naphthoyl chloride in 5 ml of chloroform. The solution is stirred at room temperature overnight, then concentrated under reduced pressure. Addition of water and ethyl acetate to the residue provides a solid, which is filtered, washed with ethyl acetate and water, and dried under vacuum to afford 200 mg of the title compound as a white solid. Η NMR (CDC13) δ 1.50, 1.4-1.8, 2.1, 3.6, 4.26, 7.3-7.6, 7.8, 8.0 ppm HRMS (m+H) 411.1875.
EXAMPLE 7 Preparation of N-[5-(Cycloheptylamino)-l,3,4-thiadiazol-2-yl]-2- methoxybenzamide.
Figure imgf000016_0001
A mixture of 5-bromo-l,3,4-thiadiazol-2-ylamine (720 mg), K2HPO4 (780 mg), and cycloheptylamine (0.51 mg) in 5 ml of DMF is stirred at 60 CC for 4 hours, then diluted with pyridine and centrifuged to remove solids. To one-half of this solution, cooled to 0 °C, is added 0.30 ml of o-anisoyl chloride. The solution is stirred at room temperature overnight, then concentrated under reduced pressure and diluted with 100 ml of water. The precipitated solid is filtered, washed with water, and dried under vacuum to afford 641 mg of the title compound. Η NMR (CDC13) δ 1.4-1.7, 2.1, 3.6, 4.09, 7.0-7.2, 7.6, 8.25 ppm HRMS m/z 346.1469.
EXAMPLE 8 Preparation of N-{5-[(2,2-Diphenylethyl)amino]-l,3,4-thiadiazol-2-yl}-2- ethoxy- 1-naphthamide.
Figure imgf000016_0002
A mixture 5-bromo-l,3,4-thiadiazol-2-ylamine (720 mg), KJHPO^ (780 mg), and 2,2-diphenylethylamine (789 mg) in 5 ml of DMF is stirred at 60 °C for 4 hours, then diluted with pyridine and centrifuged to remove solids. To one-half of this solution, cooled to 0 °C, is added a solution of 2-ethoxy-l-naphthoyl chloride (469 mg) in 5 ml of chloroform. The solution is stirred at room temperature overnight, then concentrated under reduced pressure and diluted with 100 ml of water. The resultant solid is filtered, washed with water, and dried under vacuum to provide 947 mg of the title compound.
Η NMR (CDC13) δ 1.43, 4.02, 4.15, 4.26, 4.44, 7.2-7.6, 7.8-8.0 ppm HRMS (m+H) 495.1846.
EXAMPLE 9 Preparation of 2-Ethoxy-N-(5-{[2-(lH-indol-3-yl)ethyl]amino}- 1,3,4- thiadiazol-2-yl)- 1-naphthamide.
Figure imgf000017_0001
A mixture of 5-bromo-l,3,4-thiadiazol-2-ylamine (720 mg), KjHPO,, (780 mg), and tryptamine (641 mg) in 5 ml of DMF is stirred at 60 °C for 12 hours, then diluted with pyridine and centrifuged to remove solids. To one-half of this solution, cooled to 0 °C, is added a solution of 469 mg of 2-ethoxy-l-naphthoyl chloride in 5 ml of chloroform. The solution is stirred at room temperature overnight, then concentrated under reduced pressure and diluted with 100 ml of water. The resultant solid is filtered, washed with water, and dried under vacuum to provide 866 mg of white solid. Column chromatography of 249 mg of this on silica, using 1.5-4% methanol in dichloromethane, provides 191 mg of the title compound. Η NMR (CDC13) δ 1.43, 3.16, 3.70, 4.26, 7.0-7.2, 7.3-7.4, 7.5, 7.6, 7.8, 8.0 ppm HRMS (m+H) 458.1655.
EXAMPLE 10 Preparation of N-[5-({[(2R)-6,6-Dimethylbicyclo[3.1. l]hept-2- yl]methyl}amino)-l,3,4-thiadiazol-2-yl]-2-ethoxy- 1-naphthamide.
Figure imgf000017_0002
A mixture of 5-bromo-l,3,4-tMadiazol-2-ylamine (720 mg), KjHPO4 ( 780 mg), and myrtanylamine (0.67 mg) in 5 ml of DMF is stirred at 60 °C for 12 hours, then diluted with pyridine and centrifuged to remove solids. To one-half of this solution, cooled to
0 °C, is added a solution of 2-ethoxy-l-naphthoyl chloride (469 mg) in 5 ml of chloroform. The solution is stirred at room temperature overnight, then concentrated under reduced pressure and diluted with 100 ml of water. The resultant solid is filtered, washed with water, and dried under vacuum to provide 846 mg of solid. Column chromatography of 249 mg of this on silica, using 2-4% methanol in dichloromethane, provides 220 mg of the title compound. Η NMR (CDC13) δ 1.07, 1.23, 1.44, 1.8-2.1, 2.4, 3.3, 4.27, 7.2-7.6, 7.8, 8.0 ppm HRMS (m+H) 451.2163.
EXAMPLE 11 The Following 1,3,4-Thiadiazoles of the Present Invention Are
Prepared by General Procedure Described Below. To each 48 solutions of 5-bromo-l,3,4-tMaά azol-2-ylamine (234 mg, 1.3 mmol) in
1.5 ml of DMF is added KβP04 (272 mg) and 1.3 mmol of the following amines respectively: phenethylamine, 2-nιrylmethylamine, l-(3-aminopropyl)-2-pyrrolidinone, 2-pyridmylmethylamine, N-(2-ammoethyl)-N-phenylamine, 2-(lH-mdol-3-yl)ethylamine, (^oheptylamine, cyclohexylmethylamine, ( lS,2R,5S)-6,6-dimethylbicyclo[3.1. l]hept-2- yl]methylamine, 2-(l-pyrrohdmyl)ethylamine, tetrahycko-2-furanyj netlιylamine, 4-pyridmylmethylamine, l,3-benzom )xol-5-ylmetøylamine, 2-morpholmoethylamine, 1-naphthylmethylamine, 4-fluorobenzylamine, 3-pyrichnylmethylamine, 2-piperidmoethylamine, 2-etJιymexylamine, 4-(2-ammoetiιyl)benzenesulfonamide, N-(3-aminopropyl)-N-cyclohexylamine, 3,4- 'cMorobenzylamine, 3,4-dimethoxybenzylamine, 4-phenylbutylamine, 2,2- phenylethylamine, undecylamine, 3,3-diphenylpropylamine, 2-(2-t enyl)ethylamine, 4-(ammomethyl)benzenesulfonamide, 3-(4-methylpiperazmo)propylamine, 3-aminopropanenitrile, 2-(phenylsulfanyl)ethylamine, 2-tm^nylmethylamine, N-(2-aminoethyl)acetamide, 3-( lH-imidazol-l-yl)propylamine, tert-butyl 3-aminopropanoate, cyclopropylamine, cyclopropylmethylamine, 2-(lH-iτmdazol-4-yl)ethylaπιine, 2-(ethylsulfanyl)ethylamine, cyclobutylamine, 2-( l-methyl-2-pyrro yl)ethylamine, 2,3-dihydro- lH-inden- 1-ylamine, neopentylamine, 1,2,3,4-tetrahyo ro-l-naphthalenamine, ethyl 4-aminotetrahydro-l(2H)- pyridinecarboxylate, l-benzyl-4-piperidinylamine, and N-(2-aminoethyl)-N,N- dimetiiylamine.
The resultant 48 mixtures are heated at 60 °C for 3 hours to provide a DMF solutions of the corresponding substituted aminothiadiazole intermediates. The solutions of intermediate aminothiadiazoles are diluted with pyridine to a volume of 10.0 ml, and solids are removed by centrifugation. The supernatants are aliquoted into wells of 96-well plates (0.40 ml per well) respectively, and to each well is added 0.26 ml of a 0.2 M chloroform solution of the following acid chlorides respectively:
2,4-dif.uorobenzoyl chloride, 2-methoxybenzoyl chloride, 4-bromobenzoyl chloride, 4-methylbenzoyl chloride, 5-chloropentanoyl chloride, 4-cyanobenzoyl chloride, 3-nitrobenzoyl chloride, 3,5-difiuorobenzoyl chloride, (E)-3-(2-chlorophenyl)-2-propenoyl chloride, 2-ethoxy-l-naphthoyl chloride, (Z)-9-octadecenoyl chloride, 2,6-dichlorobenzoyl chloride, 3,4-dichlorobenzoyl chloride,4-(trifluoromethyl)benzoyl chloride, (E)-3-phenyl-2-propenoyl chloride, 4-iodobenzoyl chloride, l,3-dioxcπl,3-d y(iro-2-benzofuran-5-carbonyl chloride, 4-(fluorosulfonyl)benzoyl chloride, 2,4,6-triisopropylbenzoyl chloride, 5-rΛrc 2-furoyl chloride, and l-benzothiophene-2-carbonyl chloride. The plates are shaken at intervals to effect mixing of reactants, and the acylation is allowed to proceed at room temperature overnight. Removal of the solvents in a stream of air or under vacuum then affords the compounds listed in TABLE 1.
All the amines and acid chlorides used above are either commercially available or can be easily prepared by one having ordinary skill in the organic chemistry art utilizing well known procedures.
In TABLE 1, "MS" refers to mass spectral data," % inhib" refers to percentage of inhibition at 25 uM concentration in CMV polymerase assay.
TABLE 1 MS %Inhib
1 (E)-N-(5-{[3-(cyclohexylammo)propyl]amino}- 1,3,4- thiadiazol-2-yl)-9-octadecenamide 520 100.2
2 N-(5-{[3-(cyclohexylamino)propyl]amino}- 1,3,4-thiadiazol-
2-yl)- 1,3-dioxo- l,3-dmydro-2-benzofuran-5-carboxamide — 100.1 3 N-{5-[(cyclohexylmethyl)amino]-l,3,4-thiadiazol-2-yl}- 1,3- dioxo- l,3-(lihydro-2-benzofuran-5-carboxamide 419 100.0
4 l,3-dioxo-N-[5-(undecylamino)- l,3,4-thiadiazol-2-yl]- 1,3- άΗιydro-2-benzofuran-5-carboxamide 443 100.0
5 (E)-N-(5-{[2-(l-merJιyl-2-pyrroU(unyl)ethyl]amino}- 1,3,4- thiadiazol-2-yl)-9-octadecenamide 492 99.9
6 N-{5-[(2-aιώmoethyl)an o]-l,3,4-tiιiadiazol-2-yl}-l,3- m^xo-l,3-dmy(lro-2-berιzofuran-5-carboxamide, 410 99.9 N-{5-[(4-fluoroberιzyl)amino]- l,3,4-thiadiazol-2-yl}- 1,3- m^xc-l,3-dmydro-2-berj-zofuran-5-carboxamide 399 99.8 N-{5-[(l-naphthylmethyl)amino]-l,3,4-thiadiazol-2-yl}- l,3-m^xc-l,3-dmydro-2-benzofuran-5-carboxamide 431 99.8 l,3-mrøo-N-(5-{[2-(2-t enyl)etiιyl]amino}- 1,3,4- tiτiadiazol-2-yl)-l,3-άϊhydrc>-2-benzofuran-5- carboxamide 401 99.8 N-(5-{[2-(m-mdol-3-yl)ethyl]amino}-l,3,4-thiadiazol-2- yl)- 1,3-dioxo- l,3-dmydrO-2-benzofiαran-5-carboxamide 434 99.7 l,3-moxo-N-{5-[(4-phenylbutyl)ammo]-l,3,4-thiadiazol-2- yl}- l,3-(l ydiO-2-berιzofuran-5-carboxamide 421 99.6 N-{5-[(3,4-dicMorobenzyl)amino]- l,3,4-thiadiazol-2-yl}- l,3-( oxo-l,3-dmydrcH2-berizofuran-5-carboxamide 449 99.5 N-{5-[(3,3-ά phenylpropyl)amino]-l,3,4-thiadiazol-2- yl}- 1,3-dioxo- l,3-ά yo "o-2-benzofuran-5-carboxamide 483 99.3 (E)-N-(5-{[3-(4-methylpiperazino)propyl]amino}- 1,3,4- thiadiazol-2-yl)-9-octadecenamide 521 99.0 N-(5-{[4-(aιτjinosulfonyl)phenethyl]an J_no}-l,3,4-thiadiazol- 2-yl)- 1,3-dioxo- l,3-(imydro-2-benzofuran-5-carboxamide 474 98.8 N-{5-[(3,4-chmethoxybenzyl)amino]- l,3,4-thiadiazol-2-yl}- l,3- ^xo-l,3-d ιydrcκ-2-benzofuran-5-carboxamide 441 98.7 N-{5-[(2,2-mphenyleriiyl)amino]- l,3,4-thiadiazol-2-yl}- l,3-dioxo-l,3-dmydro-2-benzofuran-5-carboxamide 471 98.6 (E)-N-(5-{[4-(ammosulfonyl)benzyl]ammo}-l,3,4- thiadiazol-2-yl)-9-octadecenamide — 98.3 (E)-N-(5-{[2-(l-pyπOhdmyl)etJιyl]amino}- 1,3,4- thiadiazol-2-yl)-9-octadecenamide 478 97.7 N-{5-[( l,3-berizcκhoxol-5-ylmethyl)amino]- 1,3,4- tmam^ol-2-yl}-l,3-dioxo-l,3-dihydro-2- benzofuran-5-carboxamide 425 97.7 l,3-dioxo-N-[5-( 1,2,3,4-tetrahydro- 1-naphthalenylamino)- l,3,4-i-bia(h^ol-2-yl]-l,3-d ydrc^2-benzofuran-5- carboxamide 421 97.4 N-[5-({[(2R)-6,6-dimethylbicyclo[3.1.1]hept-2-yl]methyl}- ammo)-l,3,4-tiu^diazol-2-yl]-2-methoxybenzamide 387 97.2 (E)-N-(5-{[2-(dimetJιylammo)eΛyl]amino}- 1,3,4-thiadiazol- 2-yl)-9-octadecenamide 452 97.0 l,3-(foxo-N-[5-(phenethylamino)- l,3,4-thiadiazol-2-yl]- l,3-(lihydro-2-berιzofuran-5-carboxamide 395 95.6 N-[5-({[(2R)-6,6-(iimethylbicyclo[3.1.1]hept-2-yl]methyl}- amino)- l,3,4-thiadiazol-2-yl]- 1,3-dioxo- l,3-dihydro-2- benzofuran-5-carboxamide 425 93.9 N-(5-{[4-(ammosιιlfonyl)benzyl]amino}- 1,3,4-thiadiazol-
2-yl)-2-ethoxy- 1-naphthamide 484 93.1 N-(5-{[3-(cyclohexylammo)propyl]amino}-l,3,4- thiadiazol-2-yl)-2-ethoxy- 1-naphthamide 454 92.9 (E)-N-[5-(cyclopropylamino)-l,3,4-thiadiazol-2-yl]-
9-octadecenamide 421 92.6 N-[5-(cycloheptylamino)-l,3,4-thiadiazol-2-yl]-l,3-dioxo- l,3-dmydro-2-benzofuran-5-carboxamide 387 92.4 N-(5-{[4-(ammosuJTonyl)benzyl]amino}- 1,3,4-thiadiazol- 2-yl)-2,6-dichlorobenzamide 458 91.8 (E)-N-[5-((ycloheptylaιrιino)-l,3,4-thiadiazol-2-yl]-9- octadecenamide 477 91.8 (E)-N-(5-{[4-(am osulfonyl)benzyl]amino}-l,3,4- thiadiazol-2-yl)-3-phenyl-2-propenamide 416 90.6 l,3-dioxo-N-(5-{[2-(phenykulfanyl)etJιyl]amino}- 1,3,4- tJ iam^ol-2-yl)-l,3-d ydrcH'2-benzofuran-5-carboxamide 425 90.1 (E)-3-(2-cMorophenyl)-N-{5-[(cyclopropylmethyl)amino]- l,3,4-thiadiazol-2-yl}-2-propenamide 335 89.9 N-(5-{[4-(ammosulfonyl)benzyl]amino}-l,3,4-thiadiazol-2- yl)-2,4,6-triisopropylbenzamide 516 89.7 N-(5-{[3-((^clohexylammo)propyl]amino}- 1,3,4-thiadiazol- 2-yl)-2,4,6-triisopropylbenzamide 486 87.6 2,6-dicMoro-N-(5-{t3-(cyclohexylammo)propyl]amino}- l,3,4-thiadiazol-2-yl)benzamide 428 87.4 (E)-N-{5-[(2,2-diphenylethyl)amino]- l,3,4-thiadiazol-2-yl}- 9-octadecenamide 561 87.3 l,3-<u^xo-N-{5-[(2-tWenyj nethyl)amino]- 1,3,4-thiadiazol- 2-yl}-l,3-dmydro-2-benzofuran-5-carboxamide 387 87.1 N-[5-(2,3-dihydrc- LH-inden- 1-ylamino)- l,3,4-thiadiazol-2- yl]-l,3-moxo-l,3-d ydro-2-benzofuran-5-carboxamide 407 86.3 (E)-N-(5-{[2-(2-tm^nyl)ethyl]amino}- l,3,4-thiadiazol-2- yl)-9-octadecenamide 491 85.7 (E)-N-{5-[(2-tiuenylmetJιyl)aιnino]- l,3,4-thiadiazol-2-yl}- 9-octadecenamide 477 84.6 N-{5-[(l,3-benzo ^xol-5-yjjnethyl)aπrino]-l,3,4-thiadiazol- 2-yl}-2-ethoxy-l-naphthamide 449 83.9 N-{5-[( l-naphthylmethyl)amino]- l,3,4-thiadiazol-2-yl}- 5-mtro-2-furamide 396 83.3 N-{5-[(l-berj^l-4-piperiάιnyl)ammo]-l,3,4-thiadiazol-2-yl}-
2-ethoxy- 1-naphthamide 488 83.1 4-cyanc-N-{5-[(3,3-ό phenylpropyl)amino]-l,3,4-thiadiazol- 2-yl}benzamide 440 82.3 N-(5-{[2-(m-mdol-3-yl)ethyl]aπmιo}-l,3,4-thiadiazol-2- yl)-5-nitro-2-furamide 399 81.6 (E)-N-{5-[(4-fluorobenzyl)amino]-l,3,4-thiadiazol-2-yl}- 9-octadecenamide 489 81.5 4-({[5-(undecylammo)-l,3,4-tJu^m^ol-2-yl]amino}- carbonyl)benzenesulfonyl fluoride — 80.3 (E)-N-(5-{[4-(armnosulfonyl)phenetiιyl]aιnino}- 1,3,4- thiadiazol-2-yl)-3-phenyl-2-propenamide 430 79.8 (E)-N-[5-(undecylamino)- l,3,4-thiadiazol-2-yl]-9- octadecenamide 535 79.5 N-{5-[(4-phenylbutyl)amino]- l,3,4-thiadiazol-2-yl}- 1- benzothiophene-2-carboxamide ... 78.7 (E)-N-{5-[( l,3-berιzodioxol-5-ylmetiιyl)amino]- 1,3,4- thiadiazol-2-yl}-9-octadecenamide 515 77.9 l,3-dioxo-N-{5-[(4-pyridmyjnethyl)amino]- 1,3,4- tMam^ol-2-yl}-l,3-dmydrcH2-ber-zofuran-5-carboxamide 382 77.7 N-{5-[(2,2-(Hphenylethyl)amino]-l,3,4-thiadiazol-2-yl}- 2-ethoxy- 1-naphthamide 495 77.6 2,6-dicMoro-N-{5-[(2,2-diphenylethyl)amino]-l,3,4- thiadiazol-2-yl}benzamide 469 77.4 N-(5-{[4-(ammosulfonyl)benzyl]arnino}- 1,3,4- thiadiazol-2-yl)-4-iodobenzamide 516 76.3 (E)-N-(5-{[2-(phenylsulfanyl)ethyl]amino}- 1,3,4- thiadiazol-2-yl)-9-octadecenamide 517 75.8 4-iodo-N-{5-[(4-phenylbutyl)amino]- 1,3,4-thiadiazol-
2-yl}benzamide 479 74.6 5-m^o-N-[5-(undecylamino)- l,3,4-thiadiazol-2-yl]- 2-furamide — 74.5 N-{5-[(3,3- phenylpropyl)amino]-l,3,4-thiadiazol-
2-yl}-2-ethoxy- 1-naphthamide 509 74.2 N-(5-{[3-(cyclohexylammo)propyl]amino}- 1,3,4- tMam^ol-2-yl)-l-benzothiophene-2-carboxamide 416 74.0 2,6-(uc oro-N-{5-[(3,3-diphenylpropyl)anτino]- l,3,4-thiadiazol-2-yl}benzamide 483 73.8 (E)-N-{5-[(3,3-(uphenylpropyl)amino]- 1,3,4- thiadiazol-2-yl}-9-octadecenamide 575 73.6 4-<yano-N-[5-(undecylamino)- 1,3,4-thiadiazol- 2-yl]benzamide 400 72.2 2-ethoxy-N-{5-[(3-pyrio nylmethyl)amino]- 1,3,4- thiadiazol-2-yl}-l-naphthamide 406 71.9 (E)-3-(2-cUorophenyl)-N-{5-[(4-fluorobenzyl)amino]- l,3,4-thiadiazol-2-yl}-2-propenamide 389 71.7 N-(5-{[4-(an mosulfonyl)phentiιyl]amino}-l,3,4- thiadiazol-2-yl)-4-iodobenzamide 530 71.1 N-{5-[(2-amlmoethyl)amino]- l,3,4-thiadiazol-2-yl}-
2-ethoxy- 1-naphthamide 434 70.6 2-ethoxy-N-{5-[(2-pyrio nyhτιetiιyl)amino]- 1,3,4- thiadiazol-2-yl}-l-naphthamide 406 70.4 2-ethoxy-N-{5-[(4-fluorobenzyl)amino]- 1,3,4- thiadiazol-2-yl}-l-naphthamide 423 69.8 (E)-N-{5-[(3-pyridmylmetJιyl)amino]-l,3,4- thiadiazol-2-yl}-9-octadecenamide 470 69.3 2,6-(U(Morc-N-{5-[(3,4-(u'cMorobenzyl)anTino]- l,3,4-thiadiazol-2-yl}benzamide 449 69.1 4-cyanc-N-{5-[(4-fluorobenzyl)amino]-l,3,4- thiadiazol-2-yl}benzamide 354 69.0 (E)-3-(2-cMorophenyl)-N-(5-{[3-(cyclohexylamino)- propyl]amiιιo}-l,3,4-thiadiazol-2-yl)-2-propenamide 420 68.8 2,6-dichloro-N-[5-( 1,2,3,4-tetrahydro- 1-naphthalenyl- aπώιo)-l,3,4-thiadiazol-2-yl]benzamide 419 68.5
77 (E)-3-phenyl-N-(5-{[2-(2-i^enyl)ethyl]amino}- 1,3,4- thiadiazol-2-yl)-2-propenamide 357 68.3
78 2-etiιoxy-N-{5-[(2-tMenyhnethyl)amino]-l,3,4-thiadiazol- 2-yl}- 1-naphthamide 411 68.2
79 tert-butyl 3-({5-t(E)-9-octadecenoylamino]- 1,3,4- tWadiazol-2-yl}amino)propanoate 68.0
80 3-nitro-N-[5-(undecylanιino)- l,3,4-thiadiazol-2-yl]- benz amide — 67.9 81 (E)-3-phenyl-N-{5-[(4-phenylbutyl)armno]-l,3,4- thiadiazol-2-yl}-2-propenamide 379 67.9
82 4-cyano-N-(5-{[2-( -mdol-3-yl)ethyl]amino}- l,3,4-thiadiazol-2-yl)benzamide 389 67.7
83 4-cyanc)-N-{5-[(2,2-mphenylethyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide 426 67.7
84 2,6-dicMoro-N-{5-[(4-pyridmylmethyl)amino]- l,3,4-thiadiazol-2-yl}benzamide 380 67.6
85 N-{5-[( l-benzyl-4-pipericlmyl)amino]- 1,3,4- thiadiazol-2-yl}- 1,3-dioxo- l,3-dihydro-2-benzofuran- 5-carboxamide 464 67.3
86 ethyl 4-[(5-{[(2-ethoxy-l-naphthyl)carbonyl]amino}- l,3,4-tiύam^ol-2-yl)amino]tetrahydro-l(2H)- pyridinecarboxylate 470 67.0
87 N-(5-{t3-( -imidazol-l-yl)propyl]amino}-l,3,4- tm^(iiazol-2-yl)-2,4,6-triisopropylbenzamide 455 67.0
88 (E)-N-(5-{[4-(ammosulfonyl)benzyl]amino}- 1,3,4- thiadiazol-2-yl)-3-(2-chlorophenyl)-2-propenamide 450 66.5
89 2-ethoxy-N-(5-{[2-( m-imidazol-4-yl)etiιyl]amino}- l,3,4-thiadiazol-2-yl)- 1-naphthamide 409 66.3 90 4-{[(5-{[2-( -mdol-3-yl)ethyl]amino}-l,3,4- tMa(U^ol-2-yl)amino]carbonyl}benzenesulfonyl fluoride 446 66.1
91 ethyl 4-({5-[(E)-9-cκ^decenoylanτino]-l,3,4-thiadiazol- 2-yl}amino)tetrahydro- l(2H)-pyridinecarboxylate 272 66.1
92 2,6-m*(^oro-N-(5-{[2-(2-tMenyl)etlιyl]amino}- 1,3,4- thiadiazol-2-yl)benzamide 399 66.1
93 2-ethoxy-N-[5-( 1,2,3,4-tetrahydro- 1-naphthalenylamino)- l,3,4-τJύadiazol-2-yl]-l-naphthamide 445 66.0
94 (E)-3-phenyl-N-{5-[(4-pyridmyJ nethyl)amino]- 1,3,4- tiιia(hazol-2-yl}-2-propenamide 338 65.9
95 N-[5-(2,3-dihydro-lH-inden- 1-ylamino)- 1,3,4-thiadiazol- 2-yl]-2-ethoxy- 1-naphthamide 431 65.9
96 N-{5-[( l,3-benzodioxol-5-ylethyl)amino]- 1,3,4-thiadiazol- 2-yl}-2,6-dichlorobenzamide 423 65.9
97 2-ethoxy-N-(5-{[2-(2-tMenyl)et ιyl]amino}- 1,3,4- thiadiazol-2-yl)- 1-naphthamide 425 65.8 98 (E)-3-(2-chlorophenyl)-N-(5-{[2-(lH-imidazol-4-yl)ethyl]- amino}-l,3,4-thiadiazol-2-yl)-2-propenamide 375 65.7
99 2,6-m'cWorr>N-(5-{[3-( -imidazol-l-yl)propyl]amino}- l,3,4-thiadiazol-2-yl)benzamide 397 65.6
100 (E)-N-{5-[(3,4-chmethoxyberιzyl)amino]- 1,3,4-thiadiazol- 2-yl}-9-octadecenamide — 65.1
101 2,6-m^moro-N-{5-[(l-naphthyJjnetJιyl)amino]-l,3,4- thiadiazol-2-yl}benzamide 429 65.0
102 4-(^an< N-(5-{[2-(2-tJu^nyl)ethyl]amino}-l,3,4- thiadiazol-2-yl)benzamide 356 64.9 103 4-(yano-N-[5-(cycloheptylamino)-l,3,4-thiadiazol-
2-yl]benzamide 342 64.9
104 N-[5-(cycloheptylamino)- l,3,4-thiadiazol-2-yl]-5- nitro-2-furamide 352 64.7
105 (E)-N-[5-(phenethylamino)- l,3,4-thiadiazol-2-yl]- 9-octadecenamide, 485 64.6
106 5-(^orc»-N-[5-(undecylamino)- l,3,4-thiadiazol-2- yl]pentanamide, 389 64.2
107 (E)-N-[5-(l,2,3,4-teta:ahydro-l-naphthalenylammo)- l,3,4-thiadiazol-2-yl]-9-octadecenamide 511 63.8 108 (E)-N-{5-[(4-phenylbutyl)amino]-l,3,4-thiadiazol-2-yl}-
9-octadecenamide 513 63.5
109 2,4,6-triisopropyl-N-(5-{[2-( l-meΛyl-2-pyrrolidinyl)ethyl] amino}- l,3,4-thiadiazol-2-yl)benzamide 458 63.4
110 (E)-N-{5-[( l-benzyl-4-piperidmyl)amino]- 1,3,4-thiadiazol- 2-yl}-3-(2-chlorophenyl)-2-propenamide 454 62.9
111 4-[({5-[(2,2- phenylethyl)amino]-l,3,4-thiadiazol-2- yl}amino)carbonyl]benzenesulfonyl fluoride 483 62.6
112 N-(5-{[3-((yclohexylarjomo)propyl]amino}- 1,3,4- t a ^ol-2-yl)-4-(taifluoromethyl)benzamide 428 62.5
113 (E)-N-{5-[((yclopiOpylmethyl)amino]-l,3,4-thiadiazol- 2-yl}-9-octadecenamide 435 62.2
114 (E)-3-phenyl-N-(5-{[2-(phenylsulfanyl)erJιyl]ammo}- l,3,4-thiadiazol-2-yl)-2-propenamide 383 62.1
115 2,6-(h'(^oro-N-t5-(2,3-almydro- -mden-l-ylamino)- l,3,4-thiadiazol-2-yl]benzamide 405 62.0 116 N-{5-[(2-et>ιy exyl)arnino]-l,3,4-thiadiazol-2-yl}- l,3- ^xc-l,3-dmydro-2-berιzofuran-5-carboxamide 401 61.9
117 (E)-N-{5-[(l,3-ber zodioxol-5-yjnethyl)amino]- l,3,4- -biadiazol-2-yl}-3-(2-chlorophenyl)-2-propenamide 415 61.5
118 2,6-m,cmoro-N-{5-[(2-tMenylmetyl)arιmo]- 1,3,4- thiadiazol-2-yl}benzamide 385 61.2
119 (E)-N-{5-[(l-naphtiιylmethyl)armno]-l,3,4-thiadiazol- 2-yl}-9-octadecenamide 521 60.6
120 tert-butyl 3-[(5-{[(E)-3-phenyl-2-propenoyl]amino}- l,3,4-tMaσ azol-2-yl)amino]propanoate 375 60.0 121 2,4-difluorcH-N-[5-(unde(ylamino)-l,3,4-thiadiazol-2- yl]benzamide 411 60.0
122 N-{5-[(3,4-dimethoxybenzyl)amino]- 1,3,4-thiadiazol- 2-yl}-2-ethoxy-l-naphthamide 465 59.5
123 (E)-N-(5-{[2-(acetylaπuno)ethyl]amino}- 1,3,4- thiadiazol-2-yl)-9-octadecenamide 466 59.2
124 (E)-N-(5-{[3-(cyclohexylammo)propyl]amino}- l,3,4-thiadiazol-2-yl)-3-phenyl-2-propenamide 386 59.2
125 (E)-N-(5-{[4-(an osulfonyl)phenet ιyl]amino}- 1,3,4- tMa(h^ol-2-yl)-3-(2-chlorophenyl)-2-propenamide 464 58.9 126 N-(5-{[3-((yclohexylarrjdno)propyl]aιmno}-l,3,4- tlύadiazol-2-yl)-5-mtro-2-iιιranτide 395 58.9
127 4-cyano-N-(5-{[3-(cyclohexylammo)propyl]amino}- l,3,4-thiadiazol-2-yl)benzamide 385 58.5
128 N-(5-{[4-(ammosulfonyl)phenethyl]amino}- 1,3,4- tm^m^ol-2-yl)-2,4,6-triisopropylbenzamide 530 58.3
129 (E)-N-(5-{[2-(ethylsulfanyl)etJιyl]amino}-l,3,4- thiadiazol-2-yl)-9-octadecenamide 469 58.3
130 (E)-N-(5-{[3-(2-oxo- l-pyrrohdinyl)propyl]amino}- l,3,4-thiadiazol-2-yl)-3-phenyl-2-propenamide 372 58.2
131 5-m^rc-N-{5-[(4-phenylbutyl)amino]-l,3,4- tMa ^ol-2-yl}-2-furamide 388 58.0
132 ethyl 4-({5-[(2,6-(u'cUorobenzoyl)amino]- 1,3,4- tMadiazol-2-yl}amino)tetrahydro- 1(2H)- pyridinecarboxylate 444 57.0
133 (E)-N-(5-{[3-( -imidazol-l-yl)propyl]amino}- l,3,4-thiadiazol-2-yl)-3-phenyl-2-propenamide 355 57.0
134 N-{5-[(3,4-climethoxybenzyl)amiιιo]-l,3,4- thiadiazol-2-yl}-4-iodobenzamide 497 56.9
135 3-nitro-N-(5- {[3-(2-oxo- l-pyrrohdinyl)propyl]- ammo}-l,3,4-thiadiazol-2-yl)benzamide 391 56.6 136 2-etiιoxy-N-{5-[(l-naphthyjjnethyl)amino]- 1,3,4- thiadiazol-2-yl}- 1-naphthamide 455 56.5
137 N-(5-{[3-((^clohexylammo)propyl]amino}-l,3,4- thiadiazol-2-yl)-3-nitrobenzamide 405 56.4
138 N-{5-[(4-phenylbutyl)amino]-l,3,4-thiadiazol-2-yl}- 4-(trifluoromeΛyl)benzamide 421 56.2
139 (E)-3-phenyl-N-{5-[(2-pyridmylmethyl)amino]- l,3,4-thiadiazol-2-yl}-2-propenamide 338 56.2
140 4-cyano-N-{5-[(3,4- *cWoroberizyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide 404 56.2 141 2-eτiιoxy-N-(5-{[2-( -mdol-3-yl)ethyl]amino}- l,3,4-thiadiazol-2-yl)-l-naphthamide 458 55.7
142 N-(5-{[4-(ammosulfonyl)phenetiιyl]amino}- 1,3,4- t adiazol-2-yl)-3,4-dichlorobenzamide 472 55.4
143 4-cyano-N-{5-[(4-phenylbutyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide 378 55.4
144 2,6-dicMoro-N-{5-[(4-fluorobenzyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide 397 55.2
145 2-etJιoxy-N-[5-(undecylamino)- 1,3,4-thiadiazol-
2-yl]-l-naphthamide 469 54.9 146 2,6-m*cmoro-N-{5-[(2-(yanoetiιyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide 342 54.8 x
147 4-iodo-N-[5-(undecylamino)- l,3,4-thiadiazol-2- yl]benzamide 501 54.7
148 N-(5-{[2-(et ιylsulfanyl)etiιyl]amino}- 1,3,4- thiadiazol-2-yl)-4-iodobenzamide 435 54.6 149 (E)-N-(5-{[2-(lH-indol-3-yl)ethyl]amino}-l,3,4- thiadiazol-2-yl)-9-octadecenamide 524 54.5
150 N-(5-{[3-(2-oxo-l-pyrrohdmyl)propyl]amino}- l,3,4-thia ^ol-2-yl)-l-berLZotrdophene-2-carboxamide 402 54.5
151 N-{5-[(l-benzyl-4-piperidmyl)arτrmo]-l,3,4-thiadiazol- 2-yl}-2,6-dichlorobenzamide 462 54.0
152 N-(5-{[4-(ammosulfonyl)phenethyl]amino}- 1,3,4- thiadiazol-2-yl)-4-bromobenzamide 484 53.9
153 (E)-N-(5-{[2-( -mdol-3-yl)ethyl]arnino}- 1,3,4- thiadiazol-2-yl)-3-phenyl-2-propenamide 390 53.7 154 (E)-3-(2-cmorophenyl)-N-{5-[(2,2-diphenylethyl)amino]- l>3,4-thiadiazol-2-yl}-2-propenamide ... 53.6
155 4-cyano-N-{5-[( l-naphthylmethyl)amino]- l,3,4-thiadiazol-2- yljbenzamide 386 53.3
156 2,6-(u"cMorc)-N-{5-[(3-pyridmylmethyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide 380 53.2
157 N-[5-(cycloheptylamino)- l,3,4-thiadiazol-2-yl]-2-ethoxy- 1- naphthamide 411 53.0
158 4-cyano-N-(5-{[3-(2-oxo-l-pyrrohdinyl)propyl]amino}- l,3,4-thiadiazol-2-yl)benzamide 371 52.9 159 4-bromo-N-(5-{[3-((yclohexylammo)propyl]amino}- 1,3,4- tiύa(h^ol-2-yl)benzamide 440 52.8
160 N-(5-{[3-(cy ohexylamino)propyl]amino}- 1,3,4- thiadiazol-2-yl)-2,4-difluorobenzamide 396 52.6
161 (E)-3-(2-cWorophenyl)-N-{5-[(2-pyridmylmethyl)amino]- l,3,4-thiadiazol-2-yl}-2-propenamide 372 51.9
162 N-(5-{[3-((ydohexylaιmno)propyl]amino}- l,3,4-thiadiazol-2- yl)-4-methylbenzamide 374 51.8
163 4-bromo-N-(5-{[2-(phenylsulfanyl)ethyl]amino}-l,3,4- thiadiazol-2-yl)benzamide 437 51.5 164 (E)-3-(2-cWorophenyl)-N-{5-[(2-tinenyjmetiιyl)ammo]-l,3,4- thiadiazol-2-yl}-2-propenamide 377 51.4 165 N-{5-[(l,3-benzooioxol-5-ylmethyl)amino]-l,3,4-thiadiazol-2- yl}-5-chloropentanamide 369 51.3
166 (E)-N-[5-((t(2R)-6,6-dimethylbicyclo[3.1. l]hept-2-yl]methyl}- anιmo)-l,3,4-thiadiazol-2-yl]-9-octadecenamide 517 51.1 167 4-methyl-N-[5-(unde(ylamino)-l,3,4-thiadiazol-2- yl]benzamide 389 50.8
168 3,4-m'chloro-N-{5-[(4-phenylbutyl)amino]- l,3,4-thiadiazol-2- yljbenzamide 421 50.8
169 2,4,6-tru^opropyl-N-(5-{t2-(l-pyrroUdmyl)ethyl]aιnino}-l,3,4- tm^m^ol-2-yl)benzamide 444 50.7
170 4-bromo-N-{5-t(4-phenylbutyl)amino]-l,3,4-thiadiazol-2- yljbenzamide 433 50.5
171 (E)-N-{5-[(2-pyridmyj^etJιyl)amino]-l,3,4-thiadiazol-2-yl}-9- octadecenamide 472 49.9 172 3,4-dic^oro-N-(5-{[3-((yclohexylaιnmo)propyl]amino}- 1,3,4- thiadiazol-2-yl)benzamide 428 49.7
173 2,4,6-trusopropyl-N-{5-[(l-naphthylmethyl)amino]-l,3,4- thiadiazol-2-yl}benzamide 487 49.5
174 2,6-m*( orc-N-{5-[(2-furylmethyl)amino]- l,3,4-thiadiazol-2- yljbenzamide 369 49.5
175 3,5-(lifluoro-N-[5-(τmdecylamino)-l,3,4-thiadiazol-2- yllbenzamide 411 49.4
176 N-{5-[(2,2-cuphenyletiιyl)aπ-ino]- l,3,4-thiadiazol-2-yl}-2,4,6- triisopropylbenzamide 527 49.4 177 N-{5-[((^clopropylmet-hyl)amino]-l,3,4-thiadiazol-2- yl}-2-ethoxy-l-naphthamide 369 49.0
178 (E)-N-{5-t(l,3-ber zodioxol-5-ylmetJιyl)amino]- 1,3,4- thiadiazol-2-yl}-3-phenyl-2-propenamide 381 49.0
179 (E)-N-{5-[(2-anil c«tJιyl)amino]- l,3,4-thiadiazol-2- yl}-9-octadecenamide 500 48.5
180 N-{5-[( l,3-benz«iioxol-5-ylmethyl)amino]- 1,3,4- tWaά azol-2-yl}-l-benzothiophene-2-carboxamide -- 48.4
181 N-{5-[( l,3-benzom^xol-5-ylme1ihyl)arjιino]- 1,3,4- thiadiazol-2-yl}-4-methylbenzamide 369 48.3 182 N-{5-[(2,2-diphenyletJιyl)amino]-l,3,4-thiadiazol-2- yl}-2,4-difluorobenzamide 437 48.2 183 5-(^oro-N-{5-[(3,3-o phenylpropyl)anιino]-l,3,4- thiadiazol-2-yl}pentanamide 429 48.1
184 l,3-dioxo-N-(5-{[3-(2-oxo- l-pyrrohdmyl)propyl]amino}- l,3,4-tWadiazol-2-yl)-l,3-dmydro-2-berιzofταran-5-carboxamide 434 47.8 185 (E)-3-(2-(Morophenyl)-N-(5-{[2-(2-tiuenyl)etJιyl]aπιino}-l,3,4- tMadiazol-2-yl)-2-propenamide 391 47.6
186 5-c >rc-N-{5-[(2,2-diphenylerJ yl)amino]- l,3,4-thiadiazol-2- yl}pentanamide 415 47.4
187 N-{5-[(2,2-diphenylethyl)amino]-l,3,4-thiadiazol-2-yl}-l- beιωothiophene-2-carboxamide — 47.2
188 N-{5-[(2,2-ά phenyletiιyl)amino]- l,3,4-thiadiazol-2- yl}-3,5-difiuorobenzamide 437 47.2
189 4-{[(5-{[3-({yclohexylaπr o)propyl]amino}-l,3,4- tWaώazol-2-yl)aπmιo](^rbonyl}benzenesulfonyl fluoride 442 47.1 190 N-{5-[(l-naphtlιylmethyl)amino]-l,3,4-thiadiazol-2- yl}-3-nitrobenzamide 406 47.1
191 3,4-m^Uoro-N-(5-{[3-(2-oxc-l-pyrroU<linyl)propyl]- ammo}-l,3,4-tm^m^ol-2-yl)benzamide 414 47.1
192 5-nitro-N-[5-( 1,2,3,4-tetrahydro- 1-naphthalenylamino)- l,3,4-thia(h^ol-2-yl]-2-ftιraιnide 386 47.0
193 (E)-3-(2-chlorophenyl)-N-(5-{[2-(ethylsulfanyl)ethyl]- amino}-l,3,4-thiadiazol-2-yl)-2-propenamide 369 46.9
194 4-bromchN-[5-(unde<ylamino)- l,3,4-thiadiazol-2- yl]benzamide 455 46.8 195 4-[({5-t(l-naphtJιylmetJιyl)amino]-l,3,4-thiadiazol-2- yl}amino)carbonyl]benzenesulfonyl fluoride 443 46.7
196 (E)-3-(2-cmorophenyl)-N-[5-(cycloheptylammo)- 1,3,4- thiadiazol-2-yl]-2-propenamide 377 46.2
197 2,4-<m uor(>-N-{5-[(4-phenylbutyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide 389 46.2
198 4-i()do-N-(5-{[2-(phenylsulfanyl)ethyl]amino}-l,3,4- thiadiazol-2-yl)benzamide — 46.0
199 (E)-N-[5-(cyclobutylanτino)-l,3,4-thiadiazol-2-yl]-9- octadecenamide 435 46.0 200 5-cMor()-N-{5-[(l-naphrJιylmetJιyl)amino]- 1,3,4- thiadiazol-2-yl}pentanamide 375 45.3 201 N-[5-(cycloheptylarτjino)-l,3,4-thiadiazol-2- yl]-3-m'trobenzamide 362 45.3
202 3,4-m*c^oro-N-(5-{[3-(lH-ir- dazol-l-yl)propyl]amino}- l,3,4-thiadiazol-2-yl)benzamide 397 45.0 203 4-iodo-N-(5-{[3-(2-oxo-l-pyrroUdmyl)propyl]amino}- l,3,4-thiadiazol-2-yl)benzamide 472 45.0
204 4-[({5-[(2-anilmoetJιyl)an ino]-l,3,4-thiadiazol-2- yl}amino)carbonyl]benzenesulfonyl fluoride 422 45.0
205 2,4-difluoro-N-(5-{[2-(phenylsulfanyl)ethyl]amino}- l,3,4-thiadiazol-2-yl)benzamide 393 44.9
206 2-etJιoxy-N-(5-{[2-(phenylsulfanyl)ethyl]amino}- 1,3,4- thiadiazol-2-yl)- 1-naphthamide 451 44.9
207 N-{5-[(3,4-m'cMorobenzyl)amino]- l,3,4-thiadiazol-2-yl}-2- ethoxy- 1-naphthamide 473 44.7 208 (E)-3-(2-chlorophenyl)-N-(5-{[3-(2-oxo-l-pyrroHdinyl)- propyl]ammo}-l,3,4-thiadiazol-2-yl)-2-propenamide 406 44.7
209 N-[5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept-2-yl]methyl}- am o)-l,3,4-tMa ^ol-2-yl]-5-nitro-2-furamide 392 44.7
210 (E)-3-(2-c_Morophenyl)-N-[5-(phenethylamino)-l,3,4- thiadiazol-2-yl]-2-propenamide 385 44.6
211 (E)-N-(5-{[2-(etiιylsulfanyl)etiιyl]amino}-l,3,4-thiadiazol- 2-yl)-3-phenyl-2-propenamide 335 44.3
212 N-(5-{[3-(cyclohexylammo)propyl]amino}-l,3,4-thiadiazol- 2-yl)-4-iodobenzamide 486 44.2 213 2-etJιoxy-N-{5-[(2-furylmetJιyl)ammo]-l,3,4-thiadiazol-2- yl}-l-naphthamide 395 44.2
214 N-{5-[(l-naphthylmethyl)amino]-l,3,4-thiadiazol-2-yl}-l- benzothiophene-2-carboxamide — 44.1
215 (E)-N-(5-{[2-( -iιmdazol-4-yl)etiιyl]amino}-l,3,4-thiadiazol- 2-yl)-3-phenyl-2-propenamide 341 44.1
216 (E)-3-(2-cMorophenyl)-N-[5-(undecylamino)-l,3,4-thiadiazol- 2-yl]-2-propenamide — 43.9
217 4-[({5-[(3,3-diphenylpropyl)armno]-l,3,4-thiadiazol-2- yl}aιnino)carbonyl]berizenesulfonyl fluoride 497 43.9 218 L-2362 N-{5-[(l-benzyl-4-piperidmyl)amino]- 1,3,4- thiadiazol-2-yl}-l-benzothiophene-2-carboxamide 450 43.6 219 N-(5-{[2-( m-mdol-3-yl)etiiyl]arn o}- l,3,4-thiadiazol-2-yl)- 2,4,6-triisopropylbenzamide 490 43.6
220 (E)-N-{5-t(2-morpholmoethyl)amino]-l,3,4-thiadiazol-2-yl}- 3-phenyl-2-propenamide 360 43.6 221 (E)-3-(2-cmorophenyl)-N-(5-{[3-( -imidazol-l-yl)propyl] aιrιmo}-l,3,4-tm^m^ol-2-yl)-2-propenamide 389 43.5
222 N-{5-[(4-pyridmylmethyl)ammo]-l,3,4-thiadiazol-2-yl}-l- benzothiophene-2-carboxamide 368 43.2
223 N-(5-{[4-(ammosu]fonyl)benzyl]amino}-l,3,4-thiadiazol-2- yl)-l-benzotbiophene-2-carboxamide 446 43.1
224 N-{5-[(2,2-diphenyletiιyl)ammo]-l,3,4-thiadiazol-2-yl}-2- methoxybenzamide 431 43.0
225 2,6-(h*cUoro-N-{5-[(4-phenylbutyl)amino]- 1,3,4-thiadiazol- 2-yl}benzamide 421 42.9 226 N-{5-[(3,3-diphenylpropyl)anaino]-l,3,4-thiadiazol-2-yl}-
3-nitrobenzamide 460 42.9
227 N-[5-(cyclopropylamino)- l,3,4-thiadiazol-2-yl]-2-ethoxy- 1- naphthamide 355 42.8
228 3,5-(Muort N-(5-{[3-(2-oxo-l-pyrroU(unyl)propyl]amino}- l,3,4-thiadiazol-2-yl)benzamide 382 42.8
229 N\(u)2\(d)-undecyl-l,3,4-tJuadiazole-2,5-diamine 271 42.5
230 N-(5-{[4-(aιrmιosulfonyl)phenethyl]aπιino}- 1,3,4-thiadiazol- 2-yl)-4-methylbenzamide 418 42.3
231 2-ethoxy-N-{5-[(4-phenylbutyl)amino]- l,3,4-thiadiazol-2-yl}- 1-naphthamide 447 42.3
232 2,4,6-triisopropyl-N-{5-[(2-piperidmoetihyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide 458 42.2
233 2-ethoxy-N-[5-(neopentylamino)- l,3,4-thiadiazol-2-yl]-
1-naphthamide 385 42.1
234 N-(5-{[2-(2-tmenyl)ethyl]aπιino}-l,3,4-thiadiazol-2-yl)-l- benzothiophene-2-carboxamide 387 42.0
235 N\(u)2\(d)-(l-naphthylmetiιyl) ,3,4-tMa ^ole-2,5-diamine 257 41.8
236 N-{5-[(2-anilmoethyl)amino]-l,3,4-thiadiazol-2-yl}-l- benzothiophene-2-carboxamide 396 41.6
237 N-{5-[(2-tmenylmethyl)amino]- l,3,4-thiadiazol-2-yl}- 1- benzothiophene-2-carboxamide 373 41.5 238 (E)-N-{5-[(2-furytoetJιyl)arnino]- l,3,4-thiadiazol-2-yl}-9- octadecenamide 461 41.5
239 4-(trifluoromethyl)-N-[5-(unde(^lamino)-l,3,4-thiadiazol-2- yUbenzamide 443 41.4 240 (E)-3-(2-cMorophenyl)-N-{5-[(3,3-diphenylpropyl)amino]- l,3,4-thiadiazol-2-yl}-2-propenamide -- 41.3
241 2,6-m'cWoro-N-{5-[(2-pyridmyjjnethyl)am o]-l,3,4-thiadiazol- 2-yl}benzamide 380 41.3
242 2-ethoxy-N-(5-{[3-(lH-imidazol-l-yl)propyl]amino}-l,3,4- tmacliazol-2-yl)-l-naphthamide 423 41.3
243 N-{5-[(3,3- phenylpropyl)amino]-l,3,4-thiadiazol-2-yl}- 2,4-difluorobenzamide 451 41.1
244 4-cyanc-N-{5-[(3,4-(limethoxybenzyl)amino]-l,3,4-thiadiazol- 2-yl}benzamide 396 41.0 245 4-[({5-[(4-phenylbutyl)arnino]-l,3,4-thiadiazol-2- yl}amino)carbonyl]benzenesulfonyl fluoride 435 41.0
246 (E)-N-{5-[(tetτahydro-2-fαranylmerJιyl)amino]-l,3,4- thiadiazol-2-yl}-9-octadecenamide 465 40.9
247 3,4-cucMoro-N-{5-[(2-iuryj^ethyU yljbenzamide 369 40.9
248 N-{5-[(2-amlm()ethyl)ammo]-l,3,4-thiadiazol-2-yl}-2,4,6- trϋsopropylbenzamide 466 40.8
249 (E)-N-{5-[(2-(^anoethyl)amino]-l,3,4-thiadiazol-2-yl}- 9-octadecenamide 432 40.6 250 N-[5-(cycloheptylaιnino)-l,3,4-thiadiazol-2-yl]-2,4,6- triisopropylbenzamide 443 40.5
251 (E)-3-(2-cMorophenyl)-N-{5-[(2-furyJ nethyl)amino]- 1,3,4- thiadiazol-2-yl}-2-propenamide 361 40.3
252 N-(5-{[2-( -mdol-3-yl)ethyl]amino}-l,3,4-thiadiazol-2-yl)- 4-iodobenzamide 490 40.2
253 (E)-N-{5-[( l-benzyl-4-pipericunyl)amino]- l,3,4-thiadiazol-2- yl}-9-octadecenamide 554 40.1
254 5-cMor( N-(5-{[2-(phenylsulfanyl)et ιyl]amino}- 1,3,4- thiadiazol-2-yl)pentanamide 371 40.0 255 2,6-dicMoro-N-(5-{[2-( -mdol-3-yl)etiιyl]aιmno}-l,3,4- thiadiazol-2-yl)benzamide 432 39.9 256 N-[5-((ydoheptylammo)-l,3,4-thiadiazol-2-yl]-l-benzothiophene- 2-carboxamide 373 39.8
257 N-[5-(unde<ylamino)- l,3,4-thiadiazol-2-yl]- 1-benzothiophene- 2-carboxamide — 39.8 258 N-(5-{[2-(a∞tylaπuno)etJιyl]aιrr o}-l,3,4-thiadiazol-2-yl)- l,3-m^xo-l,3-dmydro-2-benzofuran-5-carboxamide 376 39.7
259 N-(5-{[4-(aπm osulfonyl)phene lιyl]amino}- l,3,4-thiadiazol-2- yl)-2,6-dichlorobenzamide 472 39.6
260 2,4,6-triisopropyl-N-{5-[(4-phenylbutyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide 479 39.6
261 N-[5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept^2-yl]metiιyl}amino)- l,3,4-thiadiazol-2-yl]-2-ethoxy- 1-naphthamide 451 39.5
262 (E)-N-[5-(phenetl ylaιnino)-l,3,4-thiadiazol-2-yl]-3- phenyl-2-propenamide 351 39.5 263 3,4-m"cWor< N-{5-[(4-pyridmylmethyl)an ino]-l,3,4- thiadiazol-2-yl}benzamide 380 39.4
264 N-{5-[(2-anilmoetJιyl)amino]- l,3,4-thiadiazol-2-yl}-5- mtrc-2-furamide 375 39.2
265 N-{5-[( l-berιzyl-4-piperi(lmyl)amino]-l,3,4-thiadiazol- 2-yl}-2,4,6-triisopropylbenzamide 520 39.1
266 2,4,6-triisopropyl-N-{5-t(4-pyridmyj nethyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide 438 38.8
267 L-1768 N-(5-{[4-(arrώιosulfonyl)phenetiιyl]amino}- l,3,4-tWa ^ol-2-yl)-l-benzothiophene-2-carboxamide 460 38.7 268 (E)-3-(2-cmorophenyl)-N-(5-{[2-(m-mdol-3-yl)etJιyl]amino}- l)3,4-thiadiazol-2-yl)-2-propenamide — 38.7
269 N-(5-{[2-(m-mdol-3-yl)etiιyl]amino}-l,3,4-thiadiazol-2-yl)-l- benzothiophene-2-carboxamide -- 38.5
270 2-ethoxy-N-[5-(phenethylamino)-l,3,4-thiadiazol-2-yl]-l- naphthamide 419 38.4
271 N-(5-{[2-(m-mdol-3-yl)etιhyl]amino}-l,3,4-thiadiazol-2-yl)- 3-nitrobenzamide 409 38.4
272 4-bromo-N-(5-{[3-( -imidazol-l-yl)propyl]amino}- 1,3,4- thiadiazol-2-yl)benzamide 409 38.2 273 N-{5-[(l,3-benzc uoxol-5-ylmethyl)amino]-l,3,4-thiadiazol-
2-yl}-4-bromobenzamide 435 38.1 x
274 (E)-N-[5-((^cloheptylan-ino)-l,3,4-thiadiazol-2-yl]-3- phenyl-2-propenamide 343 38.1
275 N-(5-{[3-(cyclohexylar-imo)propyl]arximo}-l,3,4-thiadiazol-2- yl)-3,5-difluorobenzamide 396 37.9 276 (E)-3-(2-cWorophenyl)-N-[5-(cyclobutylanuno)-l,3,4- thiadiazol-2-yl]-2-propenamide 335 37.9
277 N-{5-[(3,3-diphenylpropyl)anτino]-l,3,4-thiadiazol-2- yl}- l-benzothiophene-2-carboxamide _ 37.9
278 4-({[5-((ycloheptylaπιino)- l,3,4-thiadiazol-2-yl] aιnino}carbonyl)benzenesulfonyl fluoride 399 37.5
279 (E)-N-[5-(2,3-dmydro-m-mden-l-ylamino)-l,3,4- thiadiazol-2-yl]-9-octadecenamide 497 37.4
280 2,6-di( oro-N-{5-[(3,4-dimethoxybenzyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide 439 37.3 281 N-{5-[(3,3-diphenylpropyl)amino]-l,3,4-thiadiazol-2-yl}- 3,5-difluorobenzamide 451 37.3
282 5-m^c~N-[5-(phenethylamino)-l,3,4-thiadiazol-2-yl]-2- furamide 360 37.1
283 2,6-m'(Moro-N-{5-[(2-ethy exyl)amino]- l,3,4-thiadiazol-2- yljbenzamide 401 37.0
284 N-(5-{[2-( -mdol-3-yl)etJιyl]amirιo}-l,3,4-thiadiazol- 2-yl)-4-(trifluoromethyl)benzamide 432 36.7
285 (E)-N-{5-[(cyclohexylmethyl)amino]-l,3,4-thiadiazol-2-yl}-9- octadecenamide 477 36.7 286 (E)-N-{5-[(2-etJιy exyl)ammo]-l,3,4-thiadiazol-2-yl}-9- octadecenamide 493 36.3
287 N-[5-(cyclopropylamino)-l,3,4-thiadiazol-2-yl]-l- benzothiophene-2-carboxamide 317 36.2
288 N-[5-(cycloheptylamino)- l,3,4-thiadiazol-2- yl]-4-iodobenzamide 443 36.2
289 4-iodcHN-{5-[(4-pyridmylmethyl)amino]- 1,3,4-thiadiazol- 2-yl}benzamide 438 36.0
290 (E)-N-{5-[( l-benzyl-4-piperidmyl)amino]- 1,3,4-thiadiazol- 2-yl}-3-phenyl-2-propenamide 420 35.9 291 N-{5-[(2-arrihnoethyl)amino]-l,3,4-thiadiazol-2-yl}-3- m'trobenzamide 385 35.7 292 2,6-dichloro-N-(5-{[2-(ethylsulf anyl)ethyl]amino}- 1,3,4- thiadiazol-2-yl)benzamide 377 35.6
293 tert-hntyX 3-[(5-{[(2-ethoxy-l-naphthyl)carbonyl]amino}- l,3,4-thiadiazol-2-yl)amino]propanoate 443 35.5 294 (E)-N-{5-[(2-arιilmoetiιyl)armno]-l,3,4-tWadiazol-2-yl}-
3-(2-chlorophenyl)-2-propenamide 400 35.4
295 3,4-dichloro-N-(5-{[2-( lH-mdol-3-yl)ethyl]aιnino}- 1,3,4- thiadiazol-2-yl)benzamide -~ 35.4
296 5-m'tro-N-(5-{t3-(2-oxo-l-pyrrohdmyl)propyl]amino}- 1,3,4- rJιiao azol-2-yl)-2-furamide 381 35.1
297 N-{5-[(3,3-mphenylpiOpyl)amino]-l,3,4-thiadiazol-2-yl}- 4-iodobenzamide — 35.0
298 N-{5-[(3,3-diphenylpropyl)amino]- l,3,4-thiadiazol-2-yl}- 5-rιitro-2-furamide 450 35.0 299 N-{5-[(3,3- phenylpropyl)amino]-l,3,4-thiadiazol-2- yl}-2,4,6-triisopropylbenzamide 541 34.9
300 N-[5-(cycloheptylamino)- l,3,4-thiadiazol-2-yl]-3,5- difluorobenzamide 353 34.9
301 N-{5-[(3-pyridmyJjnethyl)aιrιmo]-l,3,4-thiadiazol-2-yl}-l- benzothiophene-2-carboxamide 368 34.8
302 N-{5-[(4-fluorobenzyl)amino]- l,3,4-thiadiazol-2-yl}-3- nitrobenzamide 374 34.8
303 N-(5-{[2-( -mdol-3-yl)ethyl]aιrιino}-l,3,4-thiadiazol-2-yl)-2- methoxybenzamide 394 34.7 304 N-{5-[(cyclohexylmetJιyl)ammo]-l,3,4-thiadiazol-2-yl}-2- methoxybenzamide 347 34.6
305 N-{5-[( l,3-benzo(h^xol-5-ylmethyl)amino]- 1,3,4- thiadiazol-2-yl}-2,4-difluorobenzamide 391 34.5
306 N-{5-[(2,2-diphenylethyl)amino]- l,3,4-thiadiazol-2- yl}-5-m^c-2-furamide 436 34.4
307 4-(yano-N-[5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept-2- yl]metihyl}ammo)-l,3,4-thiadiazol-2-yl]benzamide 382 34.2
308 2,4-chcMorcHN-[5-(phenethylamino)-l,3,4-thiadiazol-2- yl]benzamide 393 34.2 309 4-bromo-N-(5-{[2-(ethylsulfanyl)eΛyl]amino}- 1,3,4- thiadiazol-2-yl)benzamide 389 34.0 310 N-[5-((ydoheptylamino)-l,3,4-thiadiazol-2-yl]-2- methoxybenzamide 347 34.0
311 N-(5-{[4-(aromosulfonyl)benzyl]amino}-l,3,4- tMam^ol-2-yl)-3,4-o (Morobenzamide 458 33.9 312 5-d or()-N-[5-({[(2R)-6,6-dimethylbicyclo[3.1.1]hept-2- yl]methyl}arn o)-l,3,4-thiadiazol-2-yl]pentanamide 371 33.9
313 (E)-N-{5-[(3,4-did lorobenzyl)amino]- l,3,4-thiadiazol-2- yl}-9-octadecenamide 539 33.9
314 N-[5-(cydobutylamino)- l,3,4-thiadiazol-2-yl]-2-ethoxy- 1- naphthamide 369 33.8
315 5-dιloro-N-{5-t((yclohexylmethyl)amino]- 1,3,4- thiadiazol-2-yl}pentanamide 331 33.8
316 5-duoro-N-[5-(cydoheptylamino)- 1,3,4- thiadiazol-2-yl]pentanamide 331 33.6 317 N-(5-{[2-(m-iιmdazol-4-yl)eΛyl]amino}-l,3,4- tMadiazol-2-yl)-2,4,6-triisopropylbenzamide 411 33.6
318 2-erJιoxy-N-(5-{[2-(ethylsulfanyl)etJιyl]amino}- 1,3,4- thiadiazol-2-yl)- 1-naphthamide 403 33.6
319 (E)-3-(2-(^orophenyl)-N-[5-(neopentylamino)-l,3,4- thiadiazol-2-yl]-2-propenamide 351 33.5
320 (E)-3-(2-chlorophenyl)-N-[5-({[(2R)-6,6-dimethylbicyclo [3.1. l]hept-2-yl]methyl}amino)- l,3,4-thiadiazol-2-yl]-2- propenamide — 33.5
321 5-cUoro-N-{5-[(4-fluorobenzyl)amino]- l,3,4-thiadiazol-2- yljpentanamide 343 33.2
322 (E)-3-(2-(Morophenyl)-N-(5-{[2-(phenylsulfanyl)ethyl]amino}- l,3,4-thiadiazol-2-yl)-2-propenamide — 33.2
323 N-[5-((ycloheptylamino)- l,3,4-thiadiazol-2-yl]-4- methylbenzamide 331 33.0 324 N^δ-ttS^m-iimdazol-l-yDpropyUaimnol-l^^- thiadiazol-2-yl)-4-iodobenzamide 455 32.9
325 5-dιloro-N-(5-{[3-(2-oxo- l-pyrroUdmyl)propyl]amino}- l,3,4-thiadiazol-2-yl)pentanamide 360 32.8
326 (E)-N-{5-[(4-fluoroberι^l)amino]-l,3,4-thiadiazol-2-yl}-3- phenyl-2-propenamide 355 32.7
327 2-methoxy-N-[5-(phenethylamino)- l,3,4-thiadiazol-2- x yl]benzamide 355 32.5
328 N-(5-{[4-(ammosulfonyl)phenethyl]amino}-l,3,4-thiadiazol- 2-yl)-2-ethoxy- 1-naphthamide 498 32.4
329 (E)-N-{5-[(l-naphthylmethyl)anaino]-l,3,4-thiadiazol-2-yl}- 3-phenyl-2-propenamide 387 32.4
330 N-(5-{[2-(m-mύdazol-4-yl)ethyl]aιnino}-l,3,4- tm^ά azol-2-yl)-l-benzotWophene-2-carboxamide 371 32.2
331 (E)-N-{5-[(3,3-mphenylpropyl)aπιino]-l,3,4-thiadiazol- 2-yl}-3-phenyl-2-propenamide — 32.1 332 N-(5-{[2-(a∞tylammo)ethyl]amino}-l,3,4-thiadiazol-2- yl)-2,4,6^triisopropylbenzamide 432 32.0
333 (E)-N-{5-[(3,4-diduorobenzyl)amino]- l,3,4-thiadiazol-2- yl}-3-phenyl-2-propenamide 405 31.9
334 2-methoxy-N-{5-[(l-naphthylmethyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide 391 31.8
335 N-(5-{[4-(ammosulfonyl)phenethyl]amino}- 1,3,4- thiadiazol-2-yl)-4-cyanobenzamide 429 31.7
336 (E)-N-(5-{[4-(aιmnosulfonyl)phenethyl]amino}-l,3,4- thiadiazol-2-yl)-9-octadecenamide — 31.6 337 3-mtrc)-N-(5-{[2-(2-tWenyl)ethyl]amino}-l,3,4- thiadiazol-2-yl)benzamide 376 31.6
338 tert-butyl 3-({5-[(2,6-dichlorobenzoyl)amino]- 1,3,4- tMaά azol-2-yl}amino)propanoate 417 31.6
339 N-{5-[(2-anilmoethyl)ammo]-l,3,4-thiadiazol-2-yl}-4- iodobenzamide 466 31.5
340 tert-butyl 3-[(5-{[(l,3-m^xc-l,3-d ydro-2-berιzofuran-5- yl)carbonyl]ammo}-l,3,4-t adiazol-2-yl)aπώιo]propanoate 419 31.5
341 N-{5-[(2-iurylmethyl)aπιino]- l,3,4-thiadiazol-2-yl}-4- iodobenzamide 427 31.3 342 (E)-3-phenyl-N-[5-(undecylamino)-l,3,4-thiadiazol-2-yl]-2- propenamide 401 31.2
343 N-[5-( 1,2,3,4-tetrahydro- 1-naphthalenylamino)- 1,3,4- thiadiazol-2-yl]-l-benzothiophene-2-carboxamide 407 31.2
344 ethyl 4-[(5-{[(E)-3-(2-d lorophenyl)-2-propenoyl]amino}- l,3,4-thiadiazol-2-yl)amino]tetrahydro- 1(2H)- pyridinecarboxylate 436 31.1 345 4-(yano-N-[5-(phenethylamino)- l,3,4-thiadiazol-2- yl]benzamide 350 30.9
346 5-chloro-N-(5-{[2-(lH-indol-3-yl)ethyl]amino}- 1,3,4- thiadiazol-2-yl)pentanamide 378 30.7 347 3-m^o-N-[5-(l,2,3,4-tetrahydrc-l-naphthalenylamino)-l,3,4- thiadiazol-2-yl]benzamide 396 30.6
348 N-{5-[(4-fluorobenzyl)amino]- l,3,4-thiadiazol-2-yl}-2- methoxybenzamide 359 30.4
349 N-{5-[(2-furylmethyl)amino]-l,3,4-thiadiazol-2-yl}-l- benzothiophene-2-carboxamide 357 30.3
350 N-{5-[(3,4- 'chlorobenzyl)amino]- l,3,4-thiadiazol-2- yl}-5-m^c-2-furamide 414 30.3
351 4-bromo-N-(5-{[2-( -mdol-3-yl)ethyl]amino}- 1,3,4- thiadiazol-2-yl)benzamide 444 30.3 352 (E)-3-(2-c^orophenyl)-N-{5-[(4-pyridmyjmethyl)amino]-l,3,4- thiadiazol-2-yl}-2-propenamide 372 30.2
353 (E)-3-(2-duorophenyl)-N-[5-((yclopropylamino)- 1,3,4- thiadiazol-2-yl]-2-propenamide 321 30.2
354 5-(^oro-N-[5-(phenethylamino)- l,3,4-thiadiazol-2-yl] pentanamide 339 29.9
355 N-[5-(2,3-d ydr( -mden-l-ylaπιino)-l,3,4-thiadiazol-2- yl]-3-nitrobenzamide 382 29.8
356 4-methyl-N-{5-[(4-phenylbutyl)amino]- l,3,4-thiadiazol-2- yDbenzamide 367 29.6 357 (E)-3-(2-chlorophenyl)-N-{5-[(4-phenylbutyl)amino]-l,3,4- thiadiazol-2-yl}-2-propenamide — 29.4
358 N-{5-[( l,3-benzodioxol-5-ylmethyl)amino]- 1,3,4- tm^diazol-2-yl}-2,4,6-triisopropylbeιιzanιide 481 29.3
359 4-methyl-N-[5-(phenethylamino)- l,3,4-tbiadiazol-2- yl]benzamide 339 29.1
360 (E)-N-{5-[(cyclohexylmethyl)aπιino]-l,3,4-thiadiazol-2- yl}-3-phenyl-2-propenamide 343 29.0
361 N-{5-[(4-fluorobeιιzyl)amino]-l,3,4-thiadiazol-2-yl}-l- benzothiophene-2-carboxamide 385 28.8 362 3,5-difluoro-N-{5-[(l-naphthyjmethyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide 397 28.8 363 2,4-difluoro-N-{5-[( l-naphthyjjnethyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide 397 28.8
364 4-<yano-N-{5-[(<ydohexylmethyl)ar no]- 1,3,4- thiadiazol-2-yl}benzamide 342 28.7 365 4-cyano-N-{5-[(2-t enylmethyl)amino]-l,3,4- thiadiazol-2-yl}benzamide 342 28.7
366 N-(5-{[4-(aπu^osulfonyl)phenethyl]amino}- 1,3,4- thiadiazol-2-yl)-2-methoxybenzamide 434 28.6
367 N-{5-[(l-benzyl-4-piperidmyl)arnino]-l,3,4- thiadiazol-2-yl}-4-iodobenzamide 520 28.6
368 ethyl 4-({5-[(l-benzothiophen-2-ylcarbonyl)amino]- l,3,4-tMadiazol-2-yl}amino)tetrahydro-l(2H)- pyridinecarboxylate 432 28.5
369 2,6-di(^oiO-N-t5-(cycloheptylamino)-l,3,4- thiadiazol-2-yl]benzamide 385 28.3
370 2,6-dichloro-N-(5-{[2-( l-pyrroh(unyl)ethyl]amino}- 1,3,4- thiadiazol-2-yl)benzamide 386 28.3
371 4-{[(5-{[3-(2-oxc-l-pyrroUo^yl)propyl]amino}-l,3,4- thiam^ol-2-yl)anτmo](^u-bonyl}benzenesulfonyl fluoride 428 28.1 372 N-{5-[(l,3-berιzc<uoxol-5-ylmethyl)amino]- 1,3,4- thia(U^ol-2-yl}-3,5-difluorobenzamide 391 28.1
373 3,5-dmuoro-N-{5-[(4-phenylbutyl)ammo]- 1,3,4- thiadiazol-2-yl}benzamide 389 28.1
374 (E)-3-(2-chlorophenyl)-N-[5-(l,2,3,4-tetrahydro-l- naphthalenylam o)-l,3,4-thiadiazol-2-yl]-2-propenamide 411 28.1
375 3,4-m'(WorcH-N-[5-(unde(ylanιino)-l,3,4-thiadiazol-2- yl]benzamide 443 27.9
376 N-{5-[(3,3-(hphenylpropyl)amino]-l,3,4-thiadiazol-2-yl}-4- (trifluoromethyl)benzamide 483 27.9 377 2,6-m"(Moro-N-[5-(phenethylamino)-l,3,4-thiadiazol-2- yllbenzamide 393 27.8
378 (E)-N-(5-{[3-( -iιmdazol-l-yl)propyl]amino}-l,3,4- thiadiazol-2-yl)-9-octadecenamide 489 27.8
379 (E)-N-{5-[(2-aιιi-inoethyl)amino]- l,3,4-thiadiazol-2- yl}-3-phenyl-2-propenamide 366 27.5
380 N-{5-[(cyclohexylmethyl)amino]- l,3,4-thiadiazol-2- yl}-5-mtro-2-furamide 352 27.5
381 2,4>6-triisopropyl-N-(5-{[3-(2-oxo- l-pyrrolidinyl)propyl]- amino}-l,3,4-thiadiazol-2-yl)berizamide 472 27.4
382 5-c^oro-N-{5-[(4-phenylbutyl)amino]-l,3,4-thiadiazol-2- yUpentanamide 367 27.3
383 N-{5-[(3,3-(Uphenylpropyl)armno]-l,3,4-thiadiazol-2- yl}-2-methoxybenzamide 445 27.3
384 3,4-di(±doro-N-{5-[((^clohexylmethyl)amino]- 1,3,4- thiadiazol-2-yl}benzaπ-ide 385 27.2 385 4-biOmo-N-{5-[(2,2-m henylethyl)amino]-l,3,4-thiadiazol-2- yljbenzamide — 27.2
386 4-bromc>-N-{5-[(3,3-mphenylpropyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide — 26.9
387 N-(5-{[3-(cyclohexylaπuno)propyl]amino}- 1,3,4- thiadiazol-2-yl)-2-methoxybenzamide 390 26.8
388 fert--butyl 3-({5-[(2,4,6-triisopropylbenzoyl)amino]- 1,3,4- trdam^ol-2-yl}amino)propanoate 475 26.6
389 N-[5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept-2-yl]methyl}- ammo)-l,3,4-tm^m^ol-2-yl]-3,5-difluorobenzamide 393 26.5 390 N-(5-{[4-(aιnmosulfonyl)phenethyl]amino}- 1,3,4- thiadiazol-2-yl)-5-chloropentanamide 418 26.3
391 (E)-N-(5-{[2-(m-imidazol-4-yl)ethyl]amino}-l,3,4- thiadiazol-2-yl)-9-octadecenamide 475 26.2
392 2,6-dicMoro-N-[5-(neopentylamino)- l,3,4-thiadiazol-2- yllbenzamide 359 26.2
393 N-{5-[(2-aιulmoethyl)anώ o]-l,3,4-thiadiazol-2-yl}-4- methylbenzamide 354 26.1
394 N-{5-[(2-anilinoethyl)amino]-l,3,4-thiadiazol-2-yl}-2- methoxybenzamide 370 26.0 395 4-methyl-N-(5-{[3-(2-oxo-l-pyιτohdmyl)propyl]amino}- l,3,4-thiadiazol-2-yl)benzamide 360 25.9
396 2,4,6-trusopropyl-N-(5-{[2-(2-tMenyl)ethyl]amino}-l,3,4- thiadiazol-2-yl)benzamide 457 25.9
397 (E)-3-(2-chlorophenyl)-N-(5-{[2-(l-pyrroHdinyl)ethyl]- amino}- l,3,4-thiadiazol-2-yl)-2-propenamide 378 25.9
398 N-(5-{[4-(ammosulfonyl)benzyl]amino}-l,3,4- tMa ^ol-2-yl)-4-(txifluoromethyl)benzamide 458 25.9
399 2,4,6-triisopropyl-N-{5-[(3-pyri(m ylmethyl)aπ-ino]- 1,3,4- thiadiazol-2-yl}benzamide 438 25.8
400 (E)-N-(5-{[2-(acetylam o)ethyl]aιnino}-l)3,4-thiadiazol-2- yl)-3-phenyl-2-propenamide 332 25.8
401 N-{5-[(4-fluorobenzyl)aπύno]-l,3,4-thiadiazol-2-yl}-2,4,6- trϋsopropylbenzamide 455 25.5
402 4-iodo-N-{5-[( l-naphthylmethyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide — 25.5 403 N-[5-({[(2R)-6,6-dimethylbicyclo[3.1.1]hept-2-yl]methyl}- anιmo)-l,3,4-tm^ ^ol-2-yl]-l-benzothiophene-2-carboxamide -- 25.3
404 N-t5-(2,3-dmydrc-m-mden-l-ylamino)-l,3,4-thiadiazol-2- yl]-5-mtro-2-furamide 372 25.2
405 N-{5-[(tetrahy(lro-2-furanyj nethyl)amino]- 1,3,4- tMadiazol-2-yl}-l-beιιzothiophene-2-carboxamide 361 25.0
406 N-(5-{[2-(ethylsulfanyl)ethyl]aπuno}-l,3,4-thiadiazol-2- yl)-4-(trifluoromethyl)benzamide 377 25.0
407 tert-butyl 3-[(5-{[4-(trifluoromethyl)benzoyl]amino}- 1,3,4- tMa(U^ol-2-yl)aπιino]propanoate 417 25.0 408 N-{5-[(2-anilmoethyl)ammo]-l,3,4-thiadiazol-2-yl}-3,4- dichlorobenzamide 408 24.9
409 N-{5-[(cyclohexylmethyl)amino]- l,3,4-thiadiazol-2-yl}-2,4,6- triisopropylbenzamide 443 24.9
410 2,6-dicMoro-N-[5-(unde(ylaιnino)-l,3,4-thiadiazol-2- yfjbenzamide 443 24.9
411 3-m^o-N-[5-(phenethylamino)-l,3,4-thiadiazol-2- yljbenzamide 370 24.8
412 N-(5-{[2-(a∞tylammo)ethyl]anτino}-l,3,4-thiadiazol-2- yl)-l-benzotbiophene-2-carboxamide 362 24.7 413 3-m^c-N-{5-[(4-phenylbutyl)amino]-l,3,4-thiadiazol-2- yl}benzamide 398 24.7
414 N-{5-[(l,3-benzodioxol-5-ylmethyl)amino]- 1,3,4- thiadiazol-2-yl}-2-methoxybenzamide 385 24.7
415 4-icdc>-N-[5-(phenethylamino)-l,3,4-thiadiazol-2-yl]benzamide 451 24.6 416 N-{5-t(3,4-(h(Moroberιzyl)amino]-l,3,4-thiadiazol-2-yl}-2,4- difluorobenzamide 415 24.5 417 3,4^di(Morc-N-{5-[(3-pyridmylmethyl)amino]-l,3,4- thiadiazol-2-yl}benzamide 380 24.4
418 3,4-dicMoro-N-t5-(cycloheptylaπ.mo)-l,3,4-thiadiazol-2- yljbenzamide 385 24.4 419 4-bromo-N-(5-{[3-(2-oxo-l-pyιτoUdmyl)piOpyl]aιnino}- l,3,4-thiadiazol-2-yl)benzamide 426 24.3
420 tert-butyl 3-({5-[(3,4-dic±dorobenzoyl)amino]-l,3,4- tMaά^azol-2-yl}amino)propanoate 417 24.1
421 (E)-3-phenyl-N-{5-[(3-pyridmyhnethyl)amino]-l,3,4- thiadiazol-2-yl}-2-propenamide 338 24.0
422 (E)-3-(2-chlorophenyl)-N-(5-{[3-(4-methylpiperazino)- prOpyl]amino}-l,3,4-thiadiazol-2-yl)-2-propenamide 421 24.0
423 2,4-(Muorc-N-{5-[(4-fluoroberιzyl)amino]-l,3,4- thiadiazol-2-yl}benzamide 365 23.8 424 2,4,6-triisopropyl-N-{5-[(2-tMenyimethyl)amino]- 1,3,4- thiadiazol-2-yl}benzamide 443 23.6
425 4-iodcHN-{5-[(2-tMenylmethyl)amino]-l,3,4-thiadiazol-2- yljbenzamide 443 23.5
426 tert-butyl 3-[(5-{[(E)-3-(2-chlorophenyl)-2-propenoyl]- ammo}-l,3,4-f amazol-2-yl)amino]propanoate 409 23.5
427 2,4-difluoro-N-(5-{[3-(2-oxo- l-pyrrolidinyl)propyl]- aιnino}-l,3,4-thiadiazol-2-yl)benzamide 382 23.4
428 2-methoxy-N-[5-( l,2,3,4-tetrahyα :o-l-naphthalenylamino)- l,3,4-thiadiazol-2-yl]benzamide 381 23.3 429 2-methoxy-N-{5-[(4-phenylbutyl)aιnino]-l,3,4-thiadiazol-2- yUbenzamide 383 23.2
430 4-icdo-N-(5-{[2-(2-tMenyl)ethyl]amino}- l,3,4-thiadiazol-2- yDbenzamide 457 23.1
431 N-{5-[((yclohexylmethyl)arnino]- l,3,4-thiadiazol-2-yl}-2- ethoxy- 1-naphthamide 411 23.1
432 (E)-3-phenyl-N-(5-{[2-( l-pyrτoMdmyl)ethyl]amino}- 1,3,4- thiadiazol-2-yl)-2-propenamide 344 23.0
433 N-{5-[((yclohexylmethyl)amino]-l,3,4-thiadiazol-2-yl}-2,4- difluorobenzamide 353 22.9 434 N-{5-[(2-aιιiJinoethyl)an3ino]-l,3,4-thiadiazol-2-yl}-4- bromobenzamide 420 22.8 435 N-{5-[(2-cyanc«thyl)aπ-ino]-l,3,4-thiadiazol-2-yl}-2,4,6- triisopropylbenzamide 400 22.8
436 N-{5-[(3,4-dimethoxybenzyl)amino]- l,3,4-thiadiazol-2- yl}-3-nitrobenzamide 416 22.8 437 3,5-difluoro-N-[5-(phenethylaπιino)-l,3,4-thiadiazol-2- yllbenzamide 361 22.7
438 N-{5-[(2-aml oethyl)aιr-mo]-l,3,4-thiadiazol-2-yl}-2,6- dichlorobenzamide 408 22.6
439 (E)-3-(2-cWorophenyl)-N-{5-[((yclohexylmethyl)amino]- l,3 -tWa(liazol-2-yl}-2-propenamide 377 22.5
440 N-[5-({[(2R)-6,6-dimethylbicyclo[3.1.1]hep1 2-yl]- methyl}amino)-l,3,4-thiadiazol-2-yl]-2,4,6- triisopropylbenzamide 483 22.5
441 2,4,6-taiisopropyl-N-[5-(unde(ylamino)- 1,3,4- thiadiazol-2-yl]benzamide 501 22.5
442 N-{5-[(2-f uylmethyl)arnmo]-l,3,4-thiadiazol-2-yl}-2,4,6- triisopropylbenzamide 427 22.3
443 (E)-3-(2-chlorophenyl)-N-{5-[( l-naphthylmethyl)ammo]- 1,3,4- thiadiazol-2-yl}-2-propenamide — 22.1 444 N-(5-{[2-((limethylaπuno)ethyl]ammo}-l,3,4-thiadiazol-2- yl)-2,4,6-triisopropylbenzamide 418 21.9
445 2,4-d uoro-N-(5-{[2-(2-thienyl)ethyl]amino}- 1,3,4- thiadiazol-2-yl)benzamide 367 21.9
446 N-(5-{[4-(aιmnosu]fonyl)phene1_hyl]amino}- 1,3,4- t a(Uazol-2-yl)-4-(tøifluoromethyl)benzamide 472 21.8
447 3,4-m'c^oro-N-(5-{[2-(e1-hykulfanyl)etiιyl]amino}- l,3,4-thiadiazol-2-yl)benzamide 377 21.6
448 2,6-dichloro-N-(5-{[2-( -imidazol-4-yl)ethyl]amino}- l,3,4-thiadiazol-2-yl)benzamide 383 21.6 449 N-{5-[(cyclohexylmethyl)an3ino]-l,3,4-thiadiazol-2-yl}-4- methylbenzamide 331 21.5
450 2-ethoxy-N-{5-[(tetrahy{ko-2-f -anyJjnethyl)amino]- 1,3,4- thiadiazol-2-yl}-l-naphthamide 399 21.4
451 3,5-difluoro-N-{5-[(4-fluorobenzyl)amino]-l,3,4- thiadiazol-2-yl}benzamide 365 21.4
452 N-{5-[(3,4-(h'(Morobenzyl)amino]-l,3,4-thiadiazol-2- yl}-2-methoxybenzamide 409 21.3
453 N-{5-[(2-morphol oethyl)amino]-l,3,4-thiadiazol-2-yl}-l- benzothiophene-2-carboxamide 390 21.2
454 N-(5-{[2-( ffi-imidazol-4-yl)ethyl]aιnino}- 1,3,4- thiadiazol-2-yl)-4-iodobenzamide 441 21.2
455 N-{5-[( l-benzyl-4-piperidmyl)amino]- l,3,4-thiadiazol-2- yl}-4-bromobenzamide 472 20.8
456 N-{5-[( l-beιαzyl-4-piperidmyl)amino]- l,3,4-thiadiazol-2- yl}-5-mtro-2-furamide 429 20.8 457 4-methyl-N-{5-[(l-naphthylmethyl)amino]-l,3,4- thiadiazol-2-yl}benzamide 375 20.7
458 3,5-difluoro-N-(5-{[2-(lH-indol-3-yl)ethyl]amino}- 1,3,4- thiadiazol-2-yl)benzamide 400 20.7
459 N-{5-[( l,3-berιzcdioxol-5-ylmethyl)amino]- 1,3,4- thiadiazol-2-yl}-4-iodobenzamide 481 20.7
460 4-[({5-[(l-benzyl-4-piperidmyl)amino]-l,3,4-thiadiazol-2- yl}amino)carbonyl]benzenesulfonyl fluoride 476 20.7
461 3,4-(udιloro-N-{5-[(2-ethy exyl)amino]- l,3,4-thiadiazol-2- yljbenzamide 401 20.6 462 N-{5-[(3,4-άιcMorobenzyl)an3ino]-l,3,4-thiadiazol-2-yl}-3- mtrobenzamide 424 20.5
463 N-(5-{[2-(a∞tylammo)ethyl]amino}- l,3,4-thiadiazol-2- yl)-2-ethoxy- 1-naphthamide 400 20.3
464 4-cyancHN-{5-[(2-morpholinoethyl)amino]- l,3,4-thiadiazol-2- yl}benzamide 359 20.3
465 (E)-N-[5-(cyclopropylamino)- l,3,4-thiadiazol-2-yl]-3- phenyl-2-propenamide 287 20.2
466 N-(5-{[2-(eώylsulfanyl)ethyl]amino}- l,3,4-thiadiazol-2- yl)-l-benzothiophene-2-carboxamide 365 20.1 467 4-ic lcHN-(5-{[3-(4-methylpiperazmo)propyl]aπιino}- l)3>4-thiadiazol-2-yl)benzamide 487 20.1
468 3,5-difluoro-N-[5-( 1,2,3,4-tetrahydro- 1-naphthalenylamino)- l,3,4-thiadiazol-2-yl]benzamide 387 20.1
469 N-{5-[(2-morpholinoethyl)amino]-l,3,4-thiadiazol-2- yl}-3-mtrobenzamide 379 20.1
470 N-{5-[(cyclopropyhnethyl)amino]-l,3,4-thiadiazol-2- yl}-4-iodobenzamide 401 20.0
471 N-{5-[(l,3-benzooioxol-5-yJ nethyl)amino]- 1,3,4- thiadiazol-2-yl}-4-cyanobenzamide 380 20.0
472 4-({[5-(phenethylammo)-l,3,4-tMam^ol-2-yl]amino}- carbonyl)benzenesulfonyl fluoride 407 20.0

Claims

WE CLAIM:
1. A compound of formula I
N -N 0
H
I or pharmaceutically acceptable ϊ salts thereof wherein:
Y is
Figure imgf000047_0001
b) /~"λ
— N X
X is a) -O-, b) -S(=O)h-,
Figure imgf000047_0002
d) -NRa-;
a) C1 8 alkyl, b) -(CHΛ-Cβ-T cycloalkyl, c) -(CHaVbicycloalkyl, d) -(CH^-M, e) -CCHaJj-W, f) -(CH2)k aryl, wherein aryl may be substituted with one to three Ra, g)
Figure imgf000047_0003
wherein het may be substituted with one to three Rg, h) -(CH^-Q, wherein Q may be substituted with one to three Rg, or i) H; R^ is a) H, b) CM alkyl, c) -C(=O)Cw alkyl, d) -S(=O)Cw alkyl, e) -COj .4 alkyl, or f) -COϋCHjphenyl;
a) halo, b) CM alkyl, c) Cl alkoxy, d) benzyl, e) -CN, f) -SO2F, g) -SO-JNHJ, h) -CF3, i) -NO2, j) -OCHJO-, k) -CO2(Cw alkyl),
1) -C(=O)CM alkyl, m) -C(=O)NH2, n) -NHCO2(CM alkyl), or o) -C(=O)-O-C(=O)-;
M is a) -CN, b) halo, c) -CO2Cw alkyl, d) -CH(phenyl)2,
Figure imgf000048_0001
f) ^ ;
W is a) -OR4) b) -SR4)
Figure imgf000048_0002
d) -NR^ ,;
R4 is a) CM alkyl, b) C3.7 cycloalkyl, or c) aryl;
Re is a) CM alkyl, b) C3.7 cycloalkyl, c) aryl, or d) -C(=O)Cw alkyl; Rg and R, are independently a) CM alkyl, or b) Rg and R? together with nitrogen form a 4- to 6-membered saturated heterocyclic moiety having one to two atoms selected from the group consistmg of oxygen, nitrogen, and sulfur; Rt is a) CW8 alkyl, b) C^ alkenyl, c) Cm alkynyl, d) C2.g alkyl substituted with one to three halo, Cw alkoxy, -OH, -SH, or -CO2H, e) C2.g alkenyl substituted with aryl, wherein the aryl may be in turn substituted with one to three ^, f) -(CrL^ aryl, wherein aryl may be substituted with one to three g, g) -(CHa Q, wherein het may be substituted with one to three Rg, or h)
Figure imgf000049_0001
wherein Q may be substituted with one to three g; aryl is phenyl or naphthyl; het is 5- to 10-membered unsaturated heterocyclic moiety having one to three atoms selected from the group consisting of oxygen, nitrogen, and sulfur;
U is 5- to 9-membered unsaturated heterocyclic moiety having one to three atoms selected from the group consisting of oxygen, nitrogen, and sulfur;
Q is 5- or 6-membered saturated heterocyclic moiety having one to two atoms selected from the group consistmg of oxygen, nitrogen, and sulfur, wherein nitrogen atom may be in turn substituted with C1-4 alkyl, phenyl, benzyl, -C(=O)Cw alkyl, or -CO2C14 alkyl; h is 0, 1, or 2; i is 0, 1, 2, 3, or 4; j is 2, 3, or 4; k is 0, 1, 2, 3, 4, 5, or 6; and with the following provisos: a) where Rg is phenyl or 4-methoxyphenyl, Rx is other than phenyl, 4-methoxyphenyl, or 4-chlorophenyl; b) where Rg is -CT^phenyl, R: is other than phenyl or -CIL^phenyl; c) where g is H, substituted or unsubstituted alkyl or phenyl, R± is other than unsubstituted alkyl or phenyl.
2. A compound of claim 1 v a) -O-, or b) - Ra
Rj is a) H, b) -CO. .4 alkyl, or
0 -COijCHa phenyl.
3. A compound of claim 1 wherein R: is a) C u alkyl, b) -{CHβ -Cj.7 cydoalkyl, c) 6,6-dimethylbicyclo[3.1. l]-2-heptyl, d) -(CH^-M, e) -(Cfl^-W, f) -(CIL^ aryl, wherein aryl may be substituted with one to three Rg, g) -(CHa^-het, wherein het may be substituted with one to three Rg, h)
Figure imgf000050_0001
wherein Q may be substituted with one to three Rg, or wherein M, aryl, Rg, i, j, and k are the same as defined in claim 1; W is a) -OR4, b) -SR4, c) -NHRj, or d) -N ^;
R4 and R5 are the same as defined in claim 1; Rg and Rγ are independently a) methyl, or b) Rg and Rγ together with nitrogen form azetidinyl, pyrrohdinyl, piperdinyl, piperazinyl, 4-methyl-l-piperazinyl, hydantoin, 4- morpholinyl, thiomorpholinyl, or 2-oxo-l-pyrrohdinyl; het is a) furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl; b) pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyranyl; c) indazolyl, benzothiazolyl, benzoimidazolyl, beiizofuryl, isobenzofuryl; benzothiazole, benzoisoxazole, benzothienyl, indolyl, isoindolyl; or d) quinolyl, isoquinolyl, qmnazolinyl, quinoxalinyl, phthalazinyl or cinnolinyl; and Q is a) 2-, 3-, or 4-piperidinyl, b) 1-, or 2-pyrrolidinyl, wherein the nitrogen atom in a) and b) may be substituted with C1A alkyl, phenyl, benzyl, or -C(=O)Cw alkyl, c) morpholinyl, d) thiomorpholinyl, e) dioxolanyl, f) imidazolidinyl, g) oxathiolanyl, h) oxazolidinyl, i) tetrahydrofuryl, or j) 2-oxo- 1-pyrrolidinyl.
4. A compound of claim 3 wherein het is furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, isoxazolyl, pyridyl, benzothienyl, or indolyl.
5. A compound of claim 3 wherein Q is l-methyl-2-pyrroUdinyl, l-methyl-4- piperidinyl, l-ethylcarboxylate-4-piperidinyl, l-benzyl-4-piperidinyl, or tetrahydrofuryl.
6. A compound of claim 1 wherein Rj is a) chloro, b) fluoro, c) methyl, d) methoxy, e) ethoxy, f) -CN, g) -SOijNI ., h) -NO2, i) -OCHjO-, or j) -C(=O)-O-C(=O)
7. A compound of claim 1 wherein Rx is a) C2.18 alkenyl, b) C2.g alkyl substituted with halo, or -CO2H, c) C2J3 alkenyl substituted with aryl, wherein the aryl may be in turn substituted with one to three halo, d) -(CΕLzX aryl, wherein aryl may be substituted with one to three Rg, or e)
Figure imgf000052_0001
wherein het may be substituted with one to three Rg; aryl and i are the same as defined in claim 1; Rg is the same as defined in claim 6; and U is a) furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl or isothiazolyl; b) pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl or pyranyl; or c) indazolyl, benzothiazolyl, benzoimidazolyl, benzofuryl, isobenzofuryl, benzothiazole, benzoisoxazole, benzothienyl, indolyl or isoindolyl.
8. A compound of claim 1 which is 1. tert-butyl 4-(5-aminc-l,3,4-thiadiazol-2-yl)tetrahydro-l(2H)- pyrazinecarboxylate,
2. N-(5-amino- l,3,4-tm^diazol-2-yl)-N-phenethylamine, N-(5-ammo-l,3,4-tm^(h^ol-2-yl)-N-butylamine,
3. 5-morpholmo-l,3,4-thiam^ol-2-ylamine, 4. tert-Butyl N-{2-[(5-ammo-l,3,4-tMam^ol-2-yl)amino]ethyl}carbamate,
5. 2-methoxy-N-[5-(phenethylammo)-l,3,4-thiadiazol-2-yl]benzamide,
6. 4-methyl-N-[5-(phenethylamino)- l,3,4-thiadiazol-2-yl]benzamide,
7. 5-chloro-N-[5-(phenethylamino)- l,3,4-thiadiazol-2-yl]pentanamide,
8. 4-cyano-N-[5-(phenethylamino)- l,3,4-thiadiazol-2-yl]benzamide, 9. 3-m^ro-N-[5-(phenethylammo)-l,3,4-thiadiazol-2-yl]benzamide,
10. 3,5-difluoro-N-[5-(phenethylamino)- l,3,4-thiadiazol-2-yl]benzamide,
11. (E)-3-(2-cWorophenyl)-N-[5-(phenethylamino)-l,3,4-thiadiazol-2-yl]-2- propenamide,
12. 2-ethoxy-N-[5-(phenethylamino)- l,3,4-thiadiazol-2-yl]- 1-naphthamide, 13. (E)-N-[5-(phenethylaιnino)-l,3,4-thiadiazol-2-yl]-9-octadecenamide,
14. 2,6-dicMorc>-N-[5-(phenethylammo)-l,3,4-thiadiazol-2-yl]benzamide,
15. 3,4-dicUorc-N-[5-(phenethylammo)-l,3,4-tMam^ol-2-yl]benzamide,
16. (E)-N-[5-(phenethylammo)-l,3,4-thiadiazol-2-yl]-3-phenyl-2-propenamide,
17. 4-iodo-N-[5-(phenethylamino)- l,3,4-thiadiazol-2-yl]benzamide, 18. l,3-dioxc-N-[5-(phenethylammo)-l,3,4-tm^ ^ol-2-yl]-l,3-dihydro-2- ber-zofuran-5-carboxamide,
19. 4-({[5-(phenethylam o)-l,3,4-tWam^ol-2-yl]ammo}carbonyl)benzenesιιlfonyl fluoride,
20. 5-nitro-N-[5-(phenethylammo)-l,3,4-tMaά^azol-2-yl]-2-furamide,
21. (E)-3-(2-dύorophenyl)-N-{5-[(2-furylmethyl)ammo]-l,3,4-thiadiazol-2-yl}-2- propenamide,
22. 2-ethoxy-N-{5-[(2-furylmethyl)amino]- l,3,4-thiadiazol-2-yl}- 1-naphthamide,
23. (E)-N-{5-[(2-fuiylmethyl)arnino]- l,3,4-thiadiazol-2-yl}-9-octadecenamide,
24. 2,6-didιloro-N-{5-[(2-furylmethyl)amino]- l,3,4-thiadiazol-2-yl}benzamide,
25. 3,4-(h'd oro-N-{5-t(2-furylmethyl)amino]- l,3,4-thiadiazol-2-yl}benzamide, 26. N-{5-[(2-furyjjnethyl)ammo]-l,3,4-tWa ^ol-2-yl}-4-iodobenzamide,
27. N-{5-[(2-:ftαrylmethyl)am o]-l,3,4-thia
28. N-{5-[(2-furylmethyl)amino]- l,3,4-thiadiazol-2-yl}- l-benzothiophene-2- carboxamide,
29. 2,4-difluoro-N-(5-{[3-(2-oxo-l-pyrroU(lmyl)propyl]ammo}-l,3,4-thiadiazol-2- yDbenzamide,
30. 4-bromo-N-(5-{[3-(2-oxcHl-pyrroUdmyl)propyl]ammo}-l,3,4-thiadiazol-2- yDbenzamide,
31. 4-methyl-N-(5-{[3-(2-oxo-l-pyrroUd yl)propyl]ammo}-l,3,4-thiadiazol-2- yDbenzamide, 32. 5-(Moro-N-(5-{[3-(2-oxo-l-pyrrohά nyl)propyl]amino}-l,3,4-thiadiazol-2- yDpentanamide,
33. 4-cyancπN-(5-{[3-(2-oxchl-pyrroUdmyl)propyl]amino}-l,3,4-thiadiazol-2- yl)benzamide,
34. 3-m^o-N-(5-{[3-(2-oxo-l-pyrrohdmyl)propyl]amino}-l,3,4-thiadiazol-2- yl)benzamide,
35. 3,5-difluoro-N-(5-{[3-(2-oxc-l-pyrτoHdmyl)propyl]aπιmo}-l,3,4-thiadiazol-2- yl)benzamide,
36. (E)-3-(2-cWorophenyl)-N-(5-{[3-(2-oxo-l-pyπroh(lmyl)propyl]amino}-l,3,4- thiadiazol-2-yl)-2-propenamide, 37. 3,4-m'chloro-N-(5-{[3-(2-oxo-l-pyrrohdmyl)propyl]ammo}-l,3,4-tihiadiazol-2- yl)benzamide,
38. (E)-N-(5-{[3-(2-oxo-l-pyrroHdmyl)propyl]ammo}-l,3,4-thiadiazol-2-yl)-3-phenyl- 2-propenamide,
39. 4-iodo-N-(5-{[3-(2-oxo- l-pyrrohdinyl)propyl]amino}- l,3,4-thiadiazol-2- yDbenzamide,
40. l,3-(hoxo-N-(5-{[3-(2-oxo-l-pyιτoUαinyl)propyl]amino}-l,3,4-thiadiazol-2-yl)-l,3- d ydro-2-benzofuran-5-carboxamide,
41. 4-{[(5-{[3-(2-oxo-l-pyrrohdmyl)propyl]amino}-l,3,4-thiadiazol-2- yl)amino]carbonyl}benzenesvιlfonyl fluoride,
42. 2,4,6-triisopropyl-N-(5-{[3-(2-oxo- l-pyrτoUdinyl)propyl]amino}- 1,3,4-thiadiazol- 2-yl)benzamide ,
43. 5-m^ro-N-(5-{[3-(2-oxo-l-pyrroUdmyl)propyl]ammo}-l,3,4-thiadiazol-2-yl)-2- furamide,
44. N-(5-{[3-(2-oxo-l-pyrroHdmyl)propyl]amino}-l,3,4-thiadiazol-2-yl)-l- benzothiophene-2-carboxamide, 45. (E)-3-(2-duorophenyl)-N-{5-t(2-pyridmylmethyl)aπm o]-l,3,4-thiadiazol-2-yl}-2- propenamide,
46. 2-ethoxy-N-{5-[(2-pyri(lmylmethyl)ammo]-l,3,4-thiadiazol-2-yl}- 1-naphthamide,
47. (E)-N-{5-[(2-pyridmylmethyl)ammo]-l,3,4-tm^diazol-2-yl}-9-octadecenamide,
48. 2,6-m'cMoro-N-{5-[(2-pyridmylmethyl)ammo]-l,3,4-thia ^ol-2-yl}benzamide, 49. (E)-3-phenyl-N-{5-[(2-pyridmylmethyl)amino]- l,3,4-thiadiazol-2-yl}-2- propenamide ,
50. N-{5-[(2-anilmoethyl)amino]- l,3,4-thiadiazol-2-yl}-2-methoxybenzamide,
51. N-{5-[(2-anilmoethyl)ammo]-l,3,4-tWa ^ol-2-yl}-4-bromobenzamide,
52. N-{5-[(2-anilinc»ethyl)ammo]-l,3,4-tMadiazol-2-yl}-4-methylbeιιzamide , 53. N-{5-[(2-anilmoethyl)ammo]-l)3,4-tm^m^ol-2-yl}-3-m^obenzamide,
54. (E)-N-{5-[(2-arιiimoethyl)ammo]-l,3,4-thiadiazol-2-yl}-3-(2-chlorophenyl)-2- propenamide,
55. N-{5-[(2-anilmoethyl)amino]-l,3,4-thiadiazol-2-yl}-2-ethoxy- 1-naphthamide,
56. (E)-N-{5-[(2-anilmoethyl)amino]- l,3,4-thiadiazol-2-yl}-9-octadecenamide, 57. N-{5-[(2-ani]inoethyl)ammo]-l,3,4-tMa ^ol-2-yl}-2,6-(u'( orobenzamide,
58. N-{5-[(2-aniJmc«thyl)amino]- l,3,4-thiadiazol-2-yl}-3,4-dichlorobenzamide,
59. (E)-N-{5-[(2-anilmoethyl)ammo]-l,3,4-tMadiazol-2-yl}-3-phenyl-2-propenamide,
60. N-{5-[(2-aniJ oethyl)amino]- l,3,4-thiadiazol-2-yl}-4-iodobenzamide,
61. N-{5-[(2-aniJmoethyl)amino]- l,3,4-thiadiazol-2-yl}- 1,3-dioxo- l,3-dihydro-2- beιιzofuran-5-carboxamide,
62. 4-[({5-[(2-anilmoethyl)amino]- l,3,4-tMadiazol-2-yl}amino)carbonyl] benzenesulfonyl fluoride,
63. N-{5-[(2-aniJinoethyl)anuno]-l,3,4-tMam^ol-2-yl}-2,4,6-trhsopropylbenzaιm
64. N-{5-[(2-anilinoethyl)amino]- l,3,4-tMadiazol-2-yl}-5-m^o-2-furamide, 65. N-{5-[(2-anil oethyl)ammo]-l,3,4-lMadi^ol-2-yl}-l-benzothiophene-2- carboxamide,
66. N-(5-{[2-(m-mdol-3-yl)etiιyl]ammo}-l,3,4-thia(iiazol-2-yl)-2- methoxybenzamide,
67. 4-bromo-N-(5-{[2-(lH-mdol-3-yl)ethyl]amino}-l,3,4-thiadiazol-2-yl)benzamide,
68. 5-dιloro-N-(5-{[2-(lH-mdol-3-yl)ethyl]ammo}-l,3,4-tMam^ol-2-yl)pentanamide, 69. 4-(yano-N-(5-{[2-(m-mdol-3-yl)ethyl]ammo}-l,3,4-lMadiazol-2-yl)benzamide,
70. N-(5-{[2-( -mdol-3-yl)ethyl]aιnino}- l,3,4-thiadiazol-2-yl)-3-nitrobenzamide,
71. 3,5-difluorc N-(5-{[2-( -mdol-3-yl)ethyl]amino}-l,3,4-thiadiazol-2- yl)benzamide,
72. (E)-3-(2-( orophenyl)-N-(5-{[2-( -mdol-3-yl)ethyl]amino}-l,3,4-thiadiazol-2- yl)-2-propenamide,
73. 2-ethoxy-N-(5-{t2-( -mdol-3-yl)ethyl]amino}-l,3,4-thiadiazol-2-yl)-l- naphthamide,
74. (E)-N-(5-{[2-( -mdol-3-yl)ethyl]amino}-l,3,4-thiadiazol-2-yl)-9- octadecenamide, 75. 2,6-m"( oro-N-(5-{[2-( -indol-3-yl)ethyl]amino}-l,3,4-thiadiazol-2- yl)benzamide,
76. 3,4-dicmoro-N-(5-{[2-(m-mdol-3-yl)ethyl]amino}-l,3,4-thiadiazol-2- yl)benzamide,
77. N-(5-{[2-(m-mdol-3-yl)ethyl]amino}-l,3,4-thiadiazol-2-yl)-4- (trifluoromethyl)benzamide,
78. (E)-N-(5-{[2-( -mdol-3-yl)ethyl]amino}-l,3,4-thiadiazol-2-yl)-3-phenyl-2- propenamide,
79. N-(5-{[2-( -indol-3-yl)ethyl]amino}- l,3,4-thiadiazol-2-yl)-4-iodobenzamide,
80. N-(5-{[2-(m-mdol-3-yl)ethyl]ammo}-l,3,4-thiadiazol-2-yl)-l,3-dioxo-l,3-dihydro-2- benzofuran-5-carboxamide,
81. 4-{[(5-{[2-(m-mdol-3-yl)etiιyl]ammo}-l,3,4-tMam^ol-2-yl)amino]carbonyl} benzenesiufonyl fluoride,
82. N-(5-{[2-(m-mdol-3-yl)etiiyl]amino}-l,3,4-thiadiazol-2-yl)-2,4,6- triisopropylbenzamide, 83. N-(5-{[2-( lH-indol-3-yl)ethyl]amino}- l,3,4-thiao azol-2-yl)-5-nitro-2-furamide,
84. N-(5-{[2-( -mdol-3-yl)ethyl]ammo}-l,3,4-tMadiazol-2-yl)-l-benzothiophene-2- carboxamide,
85. N-[5-(cycloheptylamino)- l,3,4-thiadiazol-2-yl]-2-methoxybenzamide,
86. N-[5-(cycloheptylamino)- l,3,4-thiadiazol-2-yl]-4-methylbenzamide, 87. 5-dτloro-N-[5-((ycloheptylammo)-l,3,4-thiadiazol-2-yl]pentanamide,
88. 4-cyano-N-[5-((^cloheptylammo)-l,3,4-thiadiazol-2-yl]benzamide,
89. N-[5-((ycloheptylamino)- l,3,4-thiadiazol-2-yl]-3-nitrobenzamide,
90. N-[5-(cycloheptylamino)- l,3,4-thiadiazol-2-yl]-3,5-difluorobenzamide,
91. (E)-3-(2-cUorophenyl)-N-[5-(cycloheptylamino)- l,3,4-thiadiazol-2-yl]-2- propenamide, 92. N-[5-(cycloheptylanm o)-l,3,4-tWam^ol-2-yl]-2-ethoxy-l-naphthamide,
93. (E)-N-[5-((ycloheptylamino)- l,3,4-thiadiazol-2-yl]-9-octadecenamide,
94. 2,6-m'cWorc-N-[5-(cycloheptylamino)- l,3,4-thiadiazol-2-yl]benzamide,
95. 3,4-m'cMorc-N-[5-(cycloheptylammo)-l,3,4-thiadiazol-2-yl]benzamide,
96. (E)-N-[5-((ycloheptylan_αno)-l,3,4-tMadiazol-2-yl]-3-phenyl-2-propenamide, 97. N-[5-(<ycloheptylamino)-l,3,4-thiadiazol-2-yl]-4-iodobenzamide,
98. N-[5-(cycloheptylamino)- l,3,4-thiadiazol-2-yl]- 1,3-dioxo- l,3-dihydro-2- berιzofuran-5-carboxamide,
99. 4-({[5-(cycloheptylammo)-l,3,4-tMam^ol-2-yl]ammo}carbonyl)benzenesιιlfonyl fluoride, 100. N-[5-(cycloheptylamino)- l,3,4-thiadiazol-2-yl]-2,4,6-triisopropylbenzamide,
101. N-[5-((^cloheptylamino)- l,3,4-tMa ^ol-2-yl]-5-nitrc-2-furamide,
102. N-[5-(cyclohept lamino)- l,3,4-thiadiazol-2-yl]- l-benzothiophene-2- carboxamide,
103. N-{5-[(cyclohexylmethyl)ammo]-l,3,4-tm^m^ol-2-yl}-2,4-difluorobenzamide, 104. N-{5-[(cyclohexyj nethyl)ammo]-l,3,4-tMa ^ol-2-yl}-2-methoxybenzamide,
105. N-{5-[(cyclohexyhnethyl)ammo]-l,3,4-tm^diazol-2-yl}-4-methylberιzamide,
106. 5-cMoro-N-{5-[(cyclohexylmethyl)amino]- l,3,4-thiadiazol-2-yl}pentanamide,
107. 4-(^ano-N-{5-[(cyclohexylmethyl)amino]- l,3,4-thiadiazol-2-yl}benzamide,
108. (E)-3-(2-(^orophenyl)-N-{5-[(cyclohexylmethyl)ammo]-l,3,4-thiadiazol-2-yl}-2- propenamide,
109. N-{5-[(cyclohexyjjnethyl)ammo]-l,3,4-thiadiazol-2-yl}-2-ethoxy- 1-naphthamide,
110. (E)-N-{5-[(cyclohexylmethyl)ammo]-l,3,4-tm^m^ol-2-yl}-9-octødecenamide,
111. 3,4-dicUorc)-N-{5-[(cyclohexylmethyl)ammo]-l,3,4-tm^m^ol-2-yl}benzamide,
112. (E)-N-{5-[(cyclohexylmethyl)amino]-l,3,4-thiadiazol-2-yl}-3-phenyl-2- propenamide,
113. N-{5-[(cyclohexylmethyl)aιι ιo]-l,3,4-tm^diazol-2-yl}-l,3-dioxo-l,3-d ydro-2- berizofuran-5-carboxamide,
114. N-{5-[(cyclohexylmethyl)ammo]-l,3,4-thiadiazol-2-yl}-2,4,6-triisopropyl benzamide, 115. N-{5-[(cyclohexylmethyl)arnmo]-l,3,4-t a ^ol-2-yl}-5-m^ro-2-furamide,
116. N-[5-({[(2R)-6,6-dimethylbicyclo[3.1.1]hept-2-yl]methyl}aπιmo)-l,3,4-tluadiazol- 2-yl]-2-methoxybenzamide,
117. 5-c^oro-N-[5-({[(2R)-6,6-dimethylbicyclo[3.1.1]hept-2-yl]methyl}amino)- 1,3,4- thiadiazol-2-yl]pentanamide,
118. 4-cyano-N-[5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept-2-yl]methyl}amino)- 1,3,4- thiadiazol-2-yl]benzamide,
119. N-[5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept-2-yl]methyl}amino)- 1,3,4-thiadiazol- 2-yl]-3,5-difluorobenzamide,
120. (E)-3-(2-chlorophenyl)-N-[5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept-2- yl]methyl}amino)-l,3,4-thiadiazol-2-yl]-2-propenamide, 121. N-[5-({[(2R)-6,6-dimethylbicyclo[3.1.1]hept-2-yl]methyl}ammo)-l,3)4-tMadiazol- 2-yl]-2-ethoxy- 1-naphthamide,
122. (E)-N-[5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept-2-yl]methyl}amino)- 1,3,4- thiadiazol-2-yl]-9-octadecenamide,
123. N-[5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept-2-yl]methyl}amino)- 1,3,4-thiadiazol- 2-yl]- 1,3-dioxo- l,3-d ydro-2-benzofuran-5-carboxamide,
124. N-[5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept-2-yl]metJιyl}amino)- 1,3,4-thiadiazol- 2-yl]-2,4,6-triisopropylbenzamide,
125. N-[5-({[(2R)-6,6-dimethylbicyclot3.1. l]hept-2-yl]methyl}amino)- 1,3,4-thiadiazol- 2-yl]-5-mtrc-2-furamide, 126. N-[5-({[(2R)-6,6-(limethylbicydo[3.1. l]hept-2-yl]methyl}amino)- 1,3,4-thiadiazol- 2-yl]- l-benzothiophene-2-carboxamide,
127. (E)-3-(2-cmorophenyl)-N-(5-{[2-(l-pyrroUdmyl)ethyl]aιruno}-l,3,4-thiadiazol-2- yl)-2-propenamide,
128. (E)-N-(5-{[2-(l-pyrrohdmyl)ethyl]amino}-l,3,4-thiadiazol-2-yl)-9- octadecenamide,
129. 2,6-m'(Moro-N-(5-{[2-(l-pyrroholmyl)ethyl]anm o}-l,3,4-thiadiazol-2- yl)benzamide,
130. (E)-3-phenyl-N-(5-{[2-( l-pyrrohdmyl)ethyl]amino}- l,3,4-thiadiazol-2-yl)-2- propenamide, 131. 2,4,6-trusopropyl-N-(5-{[2-(l-pyιτoU<lmyl)ethyl]aιnmo}-l,3,4-tMadiazol-2 yl)benzamide,
132. 2-ethoxy-N-{5-[(tetrahydro-2-furanyjjnethyl)aιnmo]-l,3,4-thiadiazol-2-yl}-l- naphthamide,
133. (E)-N-{5-[(tetrahydro-2-furanylmethyl)ammo]-l,3,4-ti adiazol-2-yl}-9- octadecenamide,
134. N-{5-[(tetrahydro-2-furanyJ nethyl)amino]- l,3,4-thiadiazol-2-yl}- 1- benzothiophene-2-carboxamide,
135. (E)-3-(2-cWorophenyl)-N-{5-[(4-pyridmytaethyl)amino]-l,3,4-thiadiazol-2-yl}-2- propenamide,
136. 2,6-didιloro-N-{5-[(4-pyridmyJjnethyl)amino]- l,3,4-thiadiazol-2-yl}benzamide, 137. 3,4-m'duoro-N-{5-[(4-pyridmylmethyl)ammo]-l,3,4-tm^diazol-2-yl}benzamide,
138. (E)-3-phenyl-N-{5-[(4-pyridmylmethyl)amino]- l,3,4-thiadiazol-2-yl}-2- propenamide,
139. 4-ic<lo-N-{5-[(4-pyri(mιyjjnethyl)amino]- l,3,4-thiadiazol-2-yl}benzamide,
140. l,3-dioxo-N-{5-[(4-pyridmyj nethyl)aιnmo]-l,3,4-tm^m^ol-2-yl}-l,3-dmydro-2- benzofuran-5-carboxamide,
141. 2,4,6-triisopropyl-N-{5-[(4-pyri(lmylmethyl)ammo]-l,3,4-thiam^ol-2- yljbenzamide,
142. N-{5-[(4-pyridmylmethyl)amino]- l,3,4-thiadiazol-2-yl}- l-benzothiophene-2- carboxamide, 143. N-{5-[( l,3-benzc ioxol-5-ylmethyl)amino]- l,3,4-thiadiazol-2-yl}-2,4- difluorobenzamide,
144. N-{5-[(l,3-benzom^xol-5-ylmethyl)amino]-l,3,4-thiadiazol-2-yl}-2- methoxybenzamide,
145. N-{5-[( l,3-benzom^xol-5-ylmethyl)amino]-l,3,4-thiadiazol-2-yl}-4- bromobenzamide,
146. N-{5-[(l,3-benzoo oxol-5-ylmethyl)aπιmo]-l,3,4-thiadiazol-2-yl}-4- methylbenzamide,
147. N-{5-[(l,3-benzo ^xol-5-ylmethyl)amino]-l,3,4-thiadiazol-2-yl}-5- chloropentanamide, 148. N-{5-[(l,3-benz(>m^xol-5-ylmethyl)amino]-l,3,4-thiadiazol-2-yl}-4- cyanobenz amide,
149. N-{5-[( l,3-benzo<tt\)xol-5-yJjnethyl)amino]- l,3,4-thiadiazol-2-yl}-3,5- difluorobenz amide,
150. (E)-N-{5-[( l,3-benzodioxol-5-ylmethyl)amino]- l,3,4-thiadiazol-2-yl}-3-(2- chlorophenyl)-2-propenamide,
151. N-{5-[(l,3-benzom^xol-5-ylmethyl)ammo]-l,3,4-thiadiazol-2-yl}-2-ethoxy-l- naphthamide,
152. (E)-N-{5-[(l,3-berιzomoxol-5-ylmethyl)amino]-l,3,4-thiadiazol-2-yl}-9- octadecenamide, 153. N-{5-[( l,3-benzodioxol-5-ylmethyl)amino]- l,3,4-thiadiazol-2-yl}-2,6- dichlorobenzamide,
154. (E)-N-{5-[( l,3-beιιzc)ώoxol-5-ylmethyl)aιnino]- l,3,4-thiadiazol-2-yl}-3-phenyl-2- propenamide,
155. N-{5-[(l,3-berLzom^xol-5-ylmethyl)ammo]-l,3,4-tWam^ol-2-yl}-4-iodoben_zamide,
156. N-{5-[( l,3-benzc<u^xol-5-ylmethyl)amino]- l,3,4-thiadiazol-2-yl}- 1,3-dioxo- 1,3- <i ydrc 2-benzofuran-5-carboxamide,
157. N-{5-[( l,3-benzodioxol-5-ylmethyl)amino]- l,3,4-thiadiazol-2-yl}-2,4,6- triisopropylbenzamide,
158. N-{5-[( l,3-benzom^xol-5-ylmethyl)amino]- l,3,4-thiadiazol-2-yl}- 1- benzothiophene-2-carboxamide, 159. 4-cyano-N-{5-[(2-morpholinc»ethyl)ammo]-l,3,4-tMa{u^ol-2-yl}berizamide,
160. N-{5-[(2-morpholinoethyl)amino]- l,3,4-thiadiazol-2-yl}-3-mtrobenzamide,
161. (E)-N-{5-[(2-morphol oethyl)am o]-l,3,4-thiadiazol-2-yl}-3-phenyl-2- propenamide,
162. N-{5-[(2-morpholmcιethyl)an^o]-l,3,4-tm^ ^ol-2-yl}-l-benzothiophene-2- carboxamide,
163. 2,4-difluoro-N-{5-[( l-naphthylmethyl)amino]- l,3,4-thiadiazol-2-yl}benzamide,
164. 2-methoxy-N-{5-[( l-naphthylmethyl)amino]- l,3,4-thiadiazol-2-yl}benzamide,
165. 4-methyl-N-{5-[( l-naphthylmethyl)amino]- l,3,4-thiadiazol-2-yl}benzamide,
166. 5-chloro-N-{5-[( l-naphthylmethyl)amino]- l,3,4-thiadiazol-2-yl}pentanamide, 167. 4-cyano-N-{5-[( l-naphthyJjnethyl)arnino]- l,3,4-thiadiazol-2-yl}benzamide,
168. N-{5-[( l-naphthyj nethyl)amino]- l,3,4-thiadiazol-2-yl}-3-nitrobenzamide,
169. 3,5-difluoro-N-{5-[( l-naphthylmethyl)amino]- l,3,4-thiadiazol-2-yl}benzamide,
170. (E)-3-(2-c orophenyl)-N-{5-[(l-naphthylmethyl)ammo]-l,3,4-thiadiazol-2-yl}-2- propenamide, 171. 2-ethoxy-N-{5-[(l-naphthylmethyl)ammo]-l,3,4-tMam^ol-2-yl}-l-naphthamide,
172. (E)-N-{5-[( l-naphthyj nethyl)amino]- l,3,4-thiadiazol-2-yl}-9-octadecenamide,
173. 2,6-dichloro-N-{5-[( l-naphthyj nethyl)amino]- l,3,4-thiadiazol-2-yl}benzamide,
Figure imgf000059_0001
propenamide, 175. 4-iodo-N-{5-[(l-naphthyjjnethyl)aιnmo]-l,3,4-thiam^ol-2-yl}benzamide,
176. N-{5-[( l-naphthylmetiιyl)amino]- l,3,4-thiadiazol-2-yl}- 1,3-dioxo- l,3-dihydro-2- benzofuran-5-carboxamide ,
177. 4-[({5-[( l-naphthylmethyl)ammo]-l,3,4-thiam^ol-2-yl}amino)carbonyl] benzenesulfonyl fluoride, 178. 2,4,6-triisopropyl-N-{5-[( l-naphthylmethyl)amino]- l,3,4-thiadiazol-2- yljbenzamide,
179. N-{5-[( l-naphthylmethyl)amino]- l,3,4-tm^m^ol-2-yl}-5-m^o-2-furamide,
180. N-{5-[( l-naphthylmethyl)amino]- l,3,4-thiadiazol-2-yl}- l-benzothiophene-2- carboxamide,
181. N\(u)2\(d)-(l-naphthyj nethyl)-l,3,4-thiadiazole-2,5-diamine, 182. 2,4-(Muoro-N-{5-[(4-fluorobenzyl)anιmo]-l,3,4-tWadiazol-2-yl}berjzamide,
183. N-{5-[(4-fluorobenzyl)aπιmo]-l,3,4-tMam^ol-2-yl}-2-methoxybenzamide,
184. 5-chlorc-N-{5-[(4-fluorobenzyl)amino]- l,3,4-thiadiazol-2-yl}pentanamide,
185. 4-(yanc-N-{5-[(4-fluorobenzyl)amino]- l,3,4-thiadiazol-2-yl}benzamide,
186. N-{5-[(4-fluorobenzyl)aιnmo]-l,3,4-tMadiazol-2-yl}-3-mtrobenzamide, 187. 3,5-difluoro-N-{5-[(4-fluorobenzyl)arnmo]-l,3,4-tm^m^ol-2-yl}benzamide,
188. (E)-3-(2-cMorophenyl)-N-{5-[(4-fluorobenzyl)amino]-l,3,4-thiadiazol-2-yl}-2- propenamide,
189. 2-ethoxy-N-{5-[(4-fluorobeιιzyl)amino]-l,3,4-thiadiazol-2-yl}- 1-naphthamide,
190. (E)-N-{5-[(4-fluorobenzyl)amino]- l,3,4-thiadiazol-2-yl}-9-octadecenamide, 191. 2,6-di<Moro-N-{5-[(4-fluorobenzyl)ammo]-l,3,4-tm^ ^ol-2-yl}benzamide,
192. (E)-N-{5-[(4-fluorobenzyl)aπuno]-l,3,4-thiam^ol-2-yl}-3-phenyl-2-propenamide,
193. N-{5-[(4-fluorobenzyl)ammo]-l,3,4-tMa ^ol-2-yl}-l,3-dioxo-l,3-dihydro-2- berιzofuran-5-carboxamide,
194. N-{5-[(4-fluorobenzyl)ammo]-l,3,4-tWam^ol-2-yl}-2,4,6-trusopropylbenzamide, 195. N-{5-[(4-fluorobeιιzyl)amino]- l,3,4-thiadiazol-2-yl}- l-benzothiophene-2- carboxamide,
196. 2-ethoxy-N-{5-[(3-pyridmyj nethyl)amino]- l,3,4-thiadiazol-2-yl}- 1-naphthamide,
197. (E)-N-{5-[(3-pyri(imyjjnethyl)ammo]-l,3,4-tMa ^ol-2-yl}-9-octadecenamide,
198. 2,6- 'cUoro-N-{5-[(3-pyridmylmethyl)amino]- l,3,4-thiadiazol-2-yl}benzamide, 199. 3,4-(U'( oiO-N-{5-[(3-pyridmylmethyl)ammo]-l,3,4-thiam^ol-2-yl}benzamide,
200. (E)-3-phenyl-N-{5-[(3-pyridinylmethyl)aπ.mo]-l,3,4-thiadiazol-2-yl}-2- propenamide,
201. 2,4,6-triisopropyl-N-{5-[(3-pyridmyj nethyl)ammo]-l,3,4-thiadiazol-2- yl}benzamide, 202. N-{5-[(3-pyric ιylmethyl)amino]- l,3,4-thiadiazol-2-yl}- l-benzothiophene-2- carboxamide,
203. 2,4,6-tri opropyl-N-{5-[(2-piperiά noethyl)amino]- l,3,4-thiadiazol-2- yl}benzamide,
204. (E)-N-{5-[(2-ethymexyl)amino]- l,3,4-thiadiazol-2-yl}-9-octadecenamide, 205. 2,6- 'cUoro-N-{5-[(2-ethy exyl)ammo]-l,3,4-tm^diazol-2-yl}benzamide,
206. 3,4-m^Uoro-N-{5-[(2-ethymexyl)ammo]-l,3,4-thiadiazol-2-yl}benzamide,
207. N-{5-t(2-ethy exyl)aπι o]-l,3,4-tma( ^ol-2-yl}-l,3-dioxo-l,3-d ydro-2- benzofuran-5-carboxamide,
208. N-(5-{[4-(ammosulfonyl)phenethyl]aπmιo}-l,3,4-thiadiazol-2-yl)-2- methoxybenzamide, 209. N-(5-{[4-(ammosulfonyl)phenethyl]ammo}-l,3,4-thiadiazol-2-yl)-4- bromobenzamide,
210. N-(5-{[4-(ammosulfonyl)phenethyl]ammo}-l,3,4-thiadiazol-2-yl)-4- methylbenzamide,
211. N-(5-{[4-(ammosuJfonyl)phenethyl]anιmo}-l,3,4-thiadiazol-2-yl)-5- chloropentanamide,
212. N-(5-{[4-(an_dnosulfonyl)phenethyl]ammo}-l,3,4-thiadiazol-2-yl)-4- cyanobenz amide,
213. (E)-N-(5-{[4-(ammosulfonyl)phenethyl]amino}- l,3,4-thiadiazol-2-yl)-3-(2- chlorophenyl)-2-propenamide, 214. N-(5-{[4-(ammosιιlfonyl)phenethyl]amino}- l,3,4-thiadiazol-2-yl)-2-ethoxy- 1- naphthamide,
215. (E)-N-(5-{[4-(ammosulfonyl)phenethyl]aιιmιo}- l,3,4-thiadiazol-2-yl)-9- octadecenamide,
216. N-(5-{[4-(ammosulfonyl)phenethyl]an o}-l,3,4-thiadiazol-2-yl)-2,6- dichlorobenzamide,
217. N-(5-{[4-(ammosulfonyl)phenethyl]amino}-l,3,4-thiadiazol-2-yl)-3,4- dichlorobenzamide,
218. N-(5-{[4-(ammosulfonyl)phenethyl]amino}- l,3,4-thiadiazol-2-yl)-4- (trifluoromethyl)benzamide, 219. (E)-N-(5-{[4-(ammosulfonyl)phenethyl]arnmo}-l,3,4-thiadiazol-2-yl)-3-phenyl-2- propenamide,
220. N-(5-{[4-(aιnmosulfonyl)phenethyl]an_αno}-l,3,4-thiam^ol-2-yl)-4-iodobenzamide,
221. N-(5-{[4-(ammosulfonyl)phenethyl]amino}-l,3,4-thiadiazol-2-yl)- 1,3-dioxo- 1,3- d ydro-2-benzofuran-5-carboxamide, 222. N-(5-{[4-(ammosulfonyl)phenethyl]amino}- l,3,4-thiadiazol-2-yl)-2,4,6- triisopropylbenzamide,
223. N-(5-{[4-(ammosιijfonyl)phenethyl]ammo}-l,3,4-thiadiazol-2-yl)-l- benzotbiophene-2-carboxamide,
224. N-(5-{[3-((ydohexylammo)propyl]amino}-l,3,4-thiadiazol-2-yl)-2,4- difluorobenzamide,
225. N-(5-{t3-(cyclohexylaιmno)propyl]amino}-l,3,4-thiadiazol-2-yl)-2- methoxybenzamide,
226. 4-bromo-N-(5-{[3-(cydohexylammo)propyl]aιnino}- l,3,4-thiadiazol-2- yDbenzamide,
227. N-(5-{[3-((ydohexylammo)propyl]aιnino}-l,3,4-thiadiazol-2-yl)-4- methylbenzamide,
228. 4-(yano-N-(5-{[3-(cyclohexylammo)propyl]amino}-l,3,4-thiadiazol-2- yl)benzamide,
229. N-(5-{[3-(cydohexylammo)propyl]ammo}-l,3,4-tWa ^ol-2-yl)-3-m'trobenzamide,
230. N-(5-{[3-(cyclohexylanm o)propyl]aπjino}-l,3,4-thiadiazol-2-yl)-3,5- difluorobenzamide,
231. (E)-3-(2-dιlorophenyl)-N-(5-{[3-((yclohexylaιmιιo)propyl]aιnino}-l,3,4- thiadiazol-2-yl)-2-propenamide,
232. N-(5-{[3-(cydohexylammo)propyl]ammo}-l,3,4-thiadiazol-2-yl)-2-ethoxy-l- naphthamide, 233. (E)-N-(5-{[3-(<yclohexylaιmno)propyl]amino}-l,3,4-thiadiazol-2-yl)-9- octadecenamide,
234. 2,6- 'cWorcHN-(5-{[3-((yclohexylammo)propyl]amino}- l,3,4-thiadiazol-2- yDbenzamide,
235. 3,4-dicMoro-N-(5-{[3-(cydohexylam o)propyl]amino}- l,3,4-thiadiazol-2- yDbenzamide,
236. N-(5-{[3-((yclohexylammo)propyl]aroino}-l,3,4-thiadiazol-2-yl)-4- (trifluoromethyl)benzamide,
237. (E)-N-(5-{[3-(cyclohexylarnmo)propyl]amino}-l,3,4-thiadiazol-2-yl)-3-phenyl-2- propenamide, 238. N-(5-{[3-(cyclohexylammo)propyl]aιnmo}-l,3,4-lMadiazol-2-yl)-4-iodobenzamide,
239. N-(5-{[3-(cyclohexylanαmo)propyl]ammo}-l,3,4-thiadiazol-2-yl)- 1,3-dioxo- 1,3- <lmy(lro-2-benzofuran-5-carboxamide,
240. 4-{[(5-{[3-((yclohexylan mo)propyl]amino}- l,3,4-tm^m^ol-2-yl)amino]- carbonyUbenzenesulfonyl fluoride, 241. N-(5-{[3-((yclohexylammo)propyl]anτmo}-l,3,4-thiadiazol-2-yl)-2,4,6- triisopropylbenzamide,
242. N-(5-{[3-(cyclohexylammo)propyl]amino}-l,3,4-thiadiazol-2-yl)-5-mtro-2- furamide,
243. N-(5-{[3-(cyclohexylarmno)propyl]amino}-l,3,4-thiadiazol-2-yl)-l- benzotbiophene-2-carboxamide,
244. N-{5-t(3,4-(hcMorobenzyl)aπ- o]-l,3,4-tMam^ol-2-yl}-2,4-difluorober-zanιide,
245. N-{5-[(3,4-άιcUorobeιιzyl)ammo]-l,3,4-tMa ^ol-2-yl}-2-methoxybenzamide,
246. 4-cyano-N-{5-[(3,4-o dιlorobenzyl)ammo]-l,3,4-tbia ^ol-2-yl}berιzamide,
247. N-{5-[(3,4-( (Morobeiizyl)ar no]-l,3,4-tWadiazol-2-yl}-3-nitrobenzamide)
248. N-{5-[(3,4-chclιlorobenzyl)aιmno]-l,3,4-t^ 249. (EVN-lδ-KS.^th'c^oroberizyϋaπimol-ljS^tm^ ^ol^-ylJ-θ-octadecenanaide,
250. 2,6-didύoro-N-{5-[(3,4-(Hdιloroberιzyl)ammo]-l,3,4-tm^m^ol-2-yl}benzamide,
251. (E)-N-{5-[(3,4-di(Moroberιzyl)ammo]-l,3,4-thiadiazol-2-yl}-3-phenyl-2- propenamide,
252. N-{5-[(3,4-dicl lorobenzyl)ammo]-l,3,4-tm^m^ol-2-yl}-l,3-(hoxo-l,3-dihydro-2- benzofuran-5-carboxamide,
253. N-{5-[(3,4-m"cMorobenzyl)an mo]-l,3,4-tWam^ol-2-yl}-5-nitro-2-furamide,
254. 4-cyano-N-{5-[(3,4-c methoxybenzyl)amino]- l,3,4-thiadiazol-2-yl}benzamide,
255. N-{5-[(3,4-climethoxybenzyl)amino]- l,3,4-thiadiazol-2-yl}-3-nitrobenzamide,
256. N-{5-[(3,4-dimethoxyberizyl)ammo]-l,3,4-thiadiazol-2-yl}-2-ethoxy-l- naphthamide,
257. (E)-N-{5-[(3,4-(iimethoxybenzyl)ammo]-l,3,4-tm^m^ol-2-yl}-9-octadecenamide,
258. 2,6- ^Uoro-N-{5-[(3,4-ά methoxybenzyl)ammo]-l,3,4-thiadiazol-2- yljbenzamide,
259. N-{5-[(3,4-(limethoxyber-zyl)amino]- l,3,4-thiadiazol-2-yl}-4-iodobenzamide, 260. N-{5-[(3,4-(iimethoxyberιzyl)aιιuno]
2-benzofuran-5-carboxamide,
261. 2,4-ά^uorc>-N-{5-[(4-phenylbutyl)ammo]-l,3,4-tm^m^ol-2-yl}benzamide,
262. 2-methoxy-N-{5-[(4-phenylbutyl)amino]- l,3,4-thiadiazol-2-yl}benzamide,
263. 4-bromo-N-{5-[(4-phenylbutyl)amino]- l,3,4-thiadiazol-2-yl}benzamide, 264. 4-methyl-N-{5-[(4-phenylbutyl)ammo]-l,3,4-thiadiazol-2-yl}benzamide,
265. 5-cMoro-N-{5-[(4-phenylbutyl)ammo]-l,3,4-thiadiazol-2-yl}pentanamide,
266. 4-(yano-N-{5-[(4-phenylbutyl)amino]- l,3,4-thiadiazol-2-yl}benzamide,
267. 3-m'tro-N-{5-[(4-phenylbu1yl)ammo]-l,3,4-t adiazol-2-yl}benzamide,
268. 3,5-ά^uorc)-N-{5-[(4-phenylbutyl)ammo]-l,3,4-t- ^m^ol-2-yl}benzamide, 269. (E)-3-(2-cWorophenyl)-N-{5-[(4-phenylbutyl)amino]-l,3,4-thiadiazol-2-yl}-2- propenamide,
270. 2-ethoxy-N-{5-[(4-phenylbutyl)amino]-l,3,4-thiadiazol-2-yl}- 1-naphthamide,
271. (E)-N-{5-[(4-phenylbutyl)ammo]-l,3,4-thiadiazol-2-yl}-9-octadecenamide,
272. 2,6-m'cMoro-N-{5-[(4-phenylbutyl)ammo]-l,3,4-tWadiazol-2-yl}berj_zamide, 273. 3,4-dicMoro-N-{5-[(4-phenylbutyl)ammo]-l,3,4-tMadiazol-2-yl}benzamide,
274. N-{5-[(4-phenylbutyl)ammo]-l,3,4-thia ^ol-2-yl}-4-(trifluoromethyl) benz amide,
275. (E)-3-phenyl-N-{5-[(4-phenylbutyl)an3mo]-l,3,4-t adiazol-2-yl}-2-propenamide,
276. 4-iod()-N-{5-[(4-phenylbutyl)aπuno]-l,3,4-thiadiazol-2-yl}benzamide,
277. l,3-(hoxo-N-{5-[(4-phenylbutyl)aιnmo]-l,3,4-tHam^ol-2-yl}-l,3-dihydro-2- benzofuran-5-carboxamide,
278. 4-[({5-[(4-phenylbutyl)amino]- l,3,4-thia ^ol-2-yl}amino)carbonyl] benzenesulfonyl fluoride,
279. 2,4,6-triisopropyl-N-{5-[(4-phenylbutyl)ammo]-l,3,4-thiadiazol-2-yl}benzamide,
280. 5-mtro-N-{5-[(4-phenylbutyl)amino]- l,3,4-ttøa ^ol-2-yl}-2-furamide, 281. N-{5-[(4-phenylbutyl)amino]- l,3,4-thiadiazol-2-yl}- l-benzothiophene-2- carboxamide,
282. N-{5-[(2,2-mphenylethyl)ammo]-l,3,4-tm^m^ol-2-yl}-2,4-(lifluorobenzamide,
283. N-{5-[(2,2-diphenylethyl)ammo]-l,3,4-tm^diazol-2-yl}-2-methoxybenzamide,
284. 4-bromo-N-{5-[(2,2- phenylethyl)ammo]-l,3,4-tWadiazol-2-yl}benzamide, 285. 5-(Moro-N-{5-[(2,2- phenylethyl)aπuno]-l,3,4-tm^di^ol-2-yl}pentanamide,
286. 4-cyanc-N-{5-[(2,2- phenylethyl)aπmιo]-l,3,4-thiadiazol-2-yl}benzamide,
287. N-{5-[(2,2-όiphenylethyl)anώ o]-l,3,4-tm^m^ol-2-yl}-3,5-difluorobenzamide,
288. (E)-3-(2-cmorophenyl)-N-{5-[(2,2- phenylethyl)amino]-l,3,4-thiadiazol-2-yl}-2- propenamide, 289. N-{5-[(2,2-diphenylethyl)amino]-l,3,4-thiadiazol-2-yl}-2-ethoxy- 1-naphthamide,
290. (E)-N-{5-[(2,2-cuphenylethyl)anmio]-l,3,4-tWao!iazol-2-yl}-9-octadecenamide,
291. 2,6-dicMoro-N-{5-[(2,2-diphenylethyl)ammo]-l,3,4-tWam^ol-2-yl}benzamide,
292. N-{5-[(2,2-mphenylethyl)ammo]-l,3,4-tmam^ol-2-yl}-l,3-dioxo-l,3-dmy(iro-2- beιιzofuran-5-carboxamide, 293. 4-[({5-[(2,2-mphenylethyl)amino]- l,3,4-tWam^ol-2-yl}amino)carbonyl] benzenesulfonyl fluoride,
294. N-{5-[(2,2-diphenylethyl)amino]-l,3,4-thiadiazol-2-yl}-2,4,6-triisopropyl benzamide,
295. N-{5-[(2,2-mphenylethyl)ammo]-l,3,4-tWam^ol-2-yl}-5-m^o-2-furamide, 296. N-{5-[(2,2-mphenylethyl)amino]- l,3,4-thiadiazol-2-yl}- l-benzothiophene-2- carboxamide,
297. 2,4-difluorc-N-[5-(undecylamino)- l,3,4-thiadiazol-2-yl]benzamide,
298. 4-bromo-N-[5-(undecylamino)- l,3,4-thiadiazol-2-yl]benzamide,
299. 4-methyl-N-[5-(undecylamino)- l,3,4-thiadiazol-2-yl]benzamide, 300. 5-c oro-N-[5-(unde(^lammo)-l,3,4-thiadiazol-2-yl]pentanamide,
301. 4-cyanc~N-[5-(undecylamino)- l,3,4-thiadiazol-2-yl]benzamide,
302. 3-ni1τo-N-[5-(unde(ylaπm o)-l,3,4-tMam^ol-2-yl]benzamide,
303. 3,5-(Muoro-N-[5-(undecylaπιmo)-l,3,4-tMadiazol-2-yl]benzamide,
304. (E)-3-(2-chlorophenyl)-N-t5-(undecylamino)- l,3,4-thiadiazol-2-yl]-2- propenamide, 305. 2-etiioxy-N-[5-(undecylamino)-l,3,4-thiadiazol-2-yl]- 1-naphthamide,
306. (E)-N-[5-(undecylamino)- l,3,4-thiadiazol-2-yl]-9-octadecenamide,
307. 2,6-m"diloro-N-[5-(undecylamino)- l,3,4-thiadiazol-2-yl]benzamide,
308. 3,4-m'dιloro-N-[5-(unde(ylamino)- l,3,4-thiadiazol-2-yl]benzamide,
309. 4-(trifluoromethyl)-N-[5-(unde(ylammo)-l,3,4-tMam^ol-2-yl]beiizamide, 310. (E)-3-phenyl-N-[5-(undecylamino)- l,3,4-thiadiazol-2-yl]-2-propenamide,
311. 4-iαlo-N-[5-(unde(ylaιnmo)-l,3,4-thiadiazol-2-yl]benzamide,
312. l,3-dioxo-N-[5-(undecylamino)- l,3,4-thiadiazol-2-yl]- l,3-(lmydro-2-benzofuran- 5-carboxamide,
313. 4-({[5-(undecylammo)-l,3,4-tWam^ol-2-yl]anιmo}carbonyl)benzenesulfonyl fluoride,
314. 2,4,6-triisopropyl-N-[5-(unde(ylammo)-l,3,4-tm^m^ol-2-yl]benzamide,
315. 5-mtro-N-[5-(unde<ylamino)- l,3,4-thiam^ol-2-yl]-2-furamide,
316. N-[5-(undecylammo)-l,3,4-thiadiazol-2-yl]-l-benzothiophene-2-carboxamide,
317. N-{5-[(3,3-chphenylpropyl)amino]- l,3,4-thiadiazol-2-yl}-2,4-difluorobenzamide, 318. N-{5-[(3,3-(U henylpropyl)aπιino ]- l,3,4-thiadiazol-2-yl}-2-methoxybenzamide,
319. 4-bromo-N-{5-[(3,3- ^henylpropyl)ammo]-l,3,4-thiadiazol-2-yl}benzamide,
320. 5-cWorc)-N-{5-[(3,3- ^henylpropyl)aπm o]-l,3,4-tm^m^ol-2-yl}pentanamide,
321. 4-<^ancHN-{5-[(3,3-m^henylpropyl)ammo]-l,3,4-tm^m^ol-2-yl}benzamide,
322. N-{5-[(3,3-(U^henylpropyl)ammo]-l,3,4-tMam^ol-2-yl}-3-mtrober-zamide, 323. N-{5-[(3,3-cMphenylpiOpyl)ammo]-l,3,4-tm^diazol-2-yl}-3,5-difluorobenzamide,
324. (E)-3-(2-c orophenyl)-N-{5-[(3,3-(uphenylpropyl)ammo]-l,3,4-thiadiazol-2-yl}- 2-propenamide,
325. N-{5-[(3,3-(Hphenylpropyl)arnmo]-l,3,4-thiadiazol-2-yl}-2-ethoxy-l- naphthamide, 326. (E)-N-{5-[(3,3-diphenylpropyl)ammo]-l,3,4-tm^ ^ol-2-yl}-9-octadecenamide,
327. 2,6-m^hloπ N-{5-[(3,3-diphenylpropyl)ammo]-l,3,4-tMam^ol-2-yl}benzamide,
328. N-{5-[(3,3-ώphenylpropyl)aιrιmo]-l,3,4-t a(tt^ benz amide,
329. (E)-N-{5-[(3,3-mphenylpropyl)amino]-l,3,4-thiadiazol-2-yl}-3-phenyl-2- propenamide,
330. N-{5-[(3,3-diphenylpropyl)amino]-l,3,4-thiadiazol-2-yl}-4-iodobeιιzamide,
331. N-{5-[(3,3-diphenylpropyl)arnmo]-l,3,4-thiadiazol-2-yl}-l,3-dioxo-l,3-dihydro-2- ber-Zofuran-5-carboxamide,
332. 4-[({5-[(3,3-diphenylpropyl)ammo]-l,3,4-tMam^ol-2-yl}amino)carbonyl] benzenesulfonyl fluoride, 333. N-{5-[(3,3-(Uphenylpropyl)amino]-l,3,4-thiadiazol-2-yl}-2,4,6- triisopropylbenzamide,
334. N-{5-[(3,3-(h^henylpropyl)ammo]-l,3,4-tm^m^ol-2-yl}-5-mtro-2-furamide,
335. N-{5-[(3,3-diphenylpropyl)aιmno]-l,3,4-thiadiazol-2-yl}-l-benzothiophene-2- carboxamide, 336. 2,4-(imuoro-N-(5-{[2-(2-tMenyl)ethyl]an-αno}-l,3,4-thiam^ol-2-yl)benzamide,
337. 4-(yano-N-(5-{[2-(2-tBenyl)ethyl]amino}- l,3,4-thiadiazol-2-yl)benzamide,
338. 3-nitro-N-(5-{[2-(2-thienyl)ethyl]amiιιo}- l,3,4-thiadiazol-2-yl)benzamide,
339. (E)-3-(2-cWorophenyl)-N-(5-{[2-(2-tMenyl)ethyl]ainmo}-l,3,4-thiadiazol-2-yl)-2- propenamide, 340. 2-ethoxy-N-(5-{[2-(2-thienyl)ethyl]amino}- l,3,4-thiadiazol-2-yl)- 1-naphthamide,
341. (E)-N-(5-{[2-(2-tMenyl)ethyl]ammo}-l,3,4-tmam^ol-2-yl)-9-octadecenamide,
342. 2,6-di(^oro-N-(5-{[2-(2-tMenyl)ethyl]ammo}-l,3,4-tMa ^ol-2-yl)beιιzamide,
343. (E)-3-phenyl-N-(5-{[2-(2-thienyl)ethyl]amino}-l,3,4-thiadiazol-2-yl)-2- propenamide, 344. 4-iod(>-N-(5-{[2-(2-tlύenyl)ethyl]aπmιo}-l,3,4-tHa(uazol-2-yl)beιιzamide,
345. l,3-moxo-N-(5-{[2-(2-1ι enyl)eώyl]amino}- l,3,4-thiadiazol-2-yl)- l,3-dihydro-2- beιιzofuran-5-carboxamide,
346. 2,4,6-trusopiOpyl-N-(5-{[2-(2-tMenyl)ethyl]ammo}-l,3,4-thiadiazol-2- yl)benzamide, 347. N-(5-{[2-(2-tmenyl)ethyl]ammo}-l,3,4-tmam^ol-2-yl)-l-bei)Jzothiophene-2- carboxamide,
348. (E)-N-(5-{[4-(ammosulfonyl)benzyl]amino}- l,3,4-thiadiazol-2-yl)-3-(2- chlorophenyl)-2-propenamide,
349. N-(5-{[4-(ammosulfonyl)benzyl]ammo}-l,3,4-thiadiazol-2-yl)-2-ethoxy-l- naphthamide,
350. (E)-N-(5-{[4-(an mosulfonyl)benzyl]amino}- l,3,4-thiadiazol-2-yl)-9- octadecenamide,
351. N-(5-{[4-(aπι osulfonyl)benzyl]amino}- l,3,4-thiadiazol-2-yl)-2,6- dichlorobenzamide, 352. N-(5-{[4-(anώ osulfonyl)be yl]amino}-l,3,4-thiadiazol-2-yl)-3,4- dichlorobenz amide,
353. N-(5-{[4-(aminosulf bnyl)beιιzyl]amino}- l,3,4-thiadiazol-2-yl)-4- (trifluoromethyl)benzamide,
354. (E)-N-(5-{[4-(ain osujTonyl)benzyl]ammo}-l,3,4-thiadiazol-2-yl)-3-phenyl-2- propenamide, 355. N-(5-{[4-(aπmιosu]fonyl)benzyl]amino}- l,3,4-thiadiazol-2-yl)-4-iodobenzamide,
356. N-(5-{[4-(ammosulfonyl)ber-zyl]aιnino}- l,3,4-thiadiazol-2-yl)-2,4,6- triisopropylbenzamide,
357. N-(5-{[4-(am osulfonyl)benzyl]amino}- l,3,4-thiadiazol-2-yl)- 1-benzothiophene- 2-carboxamide, 358. (E)-3-(2-duorophenyl)-N-(5-{[3-(4-methylpiperazmo)propyl]amino}- 1,3,4- thiadiazol-2-yl)-2-propenamide,
359. (E)-N-(5-{[3-(4-methylpiperazmo)propyl]aιmιιo}-l,3,4-thiadiazol-2-yl)-9- octadecenamide,
360. 4-iodo-N-(5-{[3-(4-methylpiperazmo)propyl]amino}-l,3,4-thiadiazol-2- yl)benzamide,
361. (E)-N-{5-[(2-cyanoethyl)amino]- l,3,4-thiadiazol-2-yl}-9-octadecenamide,
362. 2,6- ^Uorc N-{5-[(2-(yanoethyl)ammo]-l,3,4-tMam^ol-2-yl}beιιzamide,
363. N-{5-[(2-cyanc«ώyl)aιmno]-l,3,4-tbiam^ol-2-yl}-2,4,6-triisopropylbeιιzamide,
364. 2,4-(Muoro-N-(5-{[2-(phenykulfanyl)ethyl]ammo}-l,3,4-thiadiazol-2- yl)benzamide,
365. 4-biOmo-N-(5-{[2-(phenylsulfanyl)ethyl]ammo}-l,3,4-tWa(h^ol-2-yl)benzamide,
366. 5-cMoro-N-(5-{[2-(phenylsulfanyl)ethyl]armno}-l,3,4-tMam^ol-2-yl)pentanamide,
367. (E)-3-(2-< orophenyl)-N-(5-{[2-(phenylsulfanyl)ethyl]aπιino}-l,3,4-thiadiazol-2- yl)-2-propenamide, 368. 2-etJιoxy-N-(5-{[2-(phenylsuJ anyl)ethyl]an mo}-l,3,4-thiadiazol-2-yl)-l- naphthamide,
369. (E)-N-(5-{[2-(phenybulfanyl)ethyl]aιnino}- l,3,4-thiadiazol-2-yl)-9- octadecenamide,
370. (E)-3-phenyl-N-(5-{[2-(phenylsulfanyl)ethyl]aιnmo}-l,3,4-thiadiazol-2-yl)-2- propenamide,
371. 4-iodo-N-(5-{[2-(phenylsulfanyl)ethyl]am o}-l,3,4-tm^m^ol-2-yl)benzamide,
372. l,3-dioxo-N-(5-{[2-(phenylsulfanyl)ethyl]an^ 2-benzofuran-5-carboxamide,
373. 4-(yano-N-{5-[(2-t enylmethyl)ammo]-l,3,4-tMam^ol-2-yl}berizamide, 374. (E)-3-(2-cMorophenyl)-N-{5-[(2-thienylmethyl)amino]- l,3,4-thiadiazol-2-yl}-2- propenamide,
375. 2-ethoxy-N-{5-[(2-thienylmethyl)amino]- l,3,4-thiadiazol-2-yl}- 1-naphthamide,
376. (E)-N-{5-[(2-1_Menyj nethyl)aιnino]- l,3,4-thiadiazol-2-yl}-9-octadecenamide,
377. 2,6-όiduoπ>-N-{5-[(2-tm^nylmethyl)aπώ^
378. 4-iodo-N-{5-[(2-t enylmethyl)an mo]-l,3)4-trdadiazol-2-yl}benzaιnide, 379. l,3-dioxo-N-{5-[(2-tMenylmethyl)ammo]-l,3,4-tWam^ol-2-yl}-l,3-d ydrc-2- beιιzofuran-5-carboxamide,
380. 2,4,6-triisopropyl-N-{5-[(2-tMeny]methyl)ammo]-l,3,4-thiadiazol-2- yljbenzamide,
381. N-{5-[(2-tWenylmethιyl)ammo]-l,3,4-tHam^ol-2-yl}-l-ber-zothiophene-2- carboxamide,
382. N-(5-{[2-(acetylammo)ethyl]ammo}-l,3,4-thiadiazol-2-yl)-2-ethoxy-l- naphthamide,
383. (E)-N-(5-{[2-(a∞tylammo)ethyl]ammo}-l,3,4-tWadiazol-2-yl)-9-octade(«namide,
384. (E)-N-(5-{[2-(a∞tylammo)ethyl]amino}-l,3,4-thiadiazol-2-yl)-3-phenyl-2- propenamide,
385. N-(5-{[2-(a∞tylammo)ethyl]ammo}-l,3,4-i a ^ol-2-yl)-l,3-dioxo-l,3-dihydro- 2-berizofuran-5-carboxamide,
386. N-(5-{[2-(a∞tylaπι o)ethyl]aπuιιo}- l,3,4-thiadiazol-2-yl)-2,4,6- triisopropylbenzamide, 387. N-(5-{[2-(a∞tylammo)ethyl]aιmno}-l,3,4-tMam^ol-2-yl)-l-berizothiophene-2- carboxamide,
388. 4-bπ)mo-N-(5-{[3-( -imidazol-l-yl)propyl]an3ino}-l,3,4-thiadiazol-2- yl)benzamide,
389. (E)-3-(2-cmorophenyl)-N-(5-{[3-(m-imidazol-l-yl)propyl]amino}-l,3,4- thiadiazol-2-yl)-2-propenamide,
390. 2-ethoxy-N-(5-{[3-( -imidazol-l-yl)propyl]aπ.mo}-l,3,4-tlύadiazol-2-yl)-l- naphthamide,
391. (E)-N-(5-{[3-( -inιidazol-l-yl)propyl]amino}-l)3,4-thiadiazol-2-yl)-9- octadecenamide, 392. 2,6-didιloro-N-(5-{[3-( -imidazol-l-yl)propyl]ammo}-l,3,4-thiadiazol-2- yl)benzamide,
393. 3,4-m'duoι^N-(5-{[3-(lH-imidazol-l-yl)propyl]aπnno}-l,3,4-thiadiazol-2- yl)benzamide,
394. (E)-N-(5-{[3-( -imidazol-l-yl)propyl]ammo}-l,3,4-thiadiazol-2-yl)-3-phenyl-2- propenamide,
395. N-(5-{[3-( IH-imidazol- l-yl)propyl]aιnino}- l,3,4-thiadiazol-2-yl)-4-iodobenzamide,
396. N-(5-{[3-( -imidazol-l-yl)propyl]anιino}-l,3,4-thiadiazol-2-yl)-2,4,6- triisopropylbenzamide,
397. tert-butyl 3-[(5-{[(E)-3-(2-dιlorophenyl)-2-propenoyl]amino}- l,3,4-thiadiazol-2- yl)amino]propanoate, 398. tert-butyl 3-[(5-{[(2-ethoxy-l-naphΛyl)carbonyl]anιino}-l,3,4-tbiadiazol-2- yl)amino]propanoate,
399. tert-butyl 3-({5-[(E)-9-o(^de∞noylamino]-l,3,4-thiadiazol-2- yl}amino)propanoate,
400. tert-butyl 3-({5-[(2,6-diduorobenzoyl)amino]-l,3,4-thiadiazol-2- yl}amino)propanoate,
401. tert-butyl 3-({5-[(3,4-m'c^orobenzoyl)amino]-l,3,4-thiadiazol-2- yl}amino)propanoate,
402. tert-butyl 3-[(5-{[4-(trifluoromethyl)benzoyl]amino}-l,3,4-thiadiazol-2- yl)amino]propanoate, 403. tert-butyl 3-[(5-{[(E)-3-phenyl-2-propenoyl]amino}-l,3,4-thiadiazol-2- yl)amino]propanoate,
404. tert-butyl 3-[(5-{[( 1,3-dioxo- l,3-(l ydro-2-berιzofιιran-5-yl)carbonyl]amino}- l,3,4-thia azol-2-yl)amino]propanoate,
405. tert-butyl 3-({5-[(2,4,6-trii5opropylberjzoyl)arnino]-l,3,4-thiadiazol-2- yl}amino)propanoate,
406. (E)-3-(2-cWorophenyl)-N-[5-((yclopropylamino)-l,3,4-thiadiazol-2-yl]-2- propenamide,
407. N-[5-(cycloprOpylamino)- l,3,4-thiadiazol-2-yl]-2-ethoxy- 1-naphthamide,
408. (E)-N-[5-(cydopropylammo)-l,3,4-thiadiazol-2-yl]-9-octadecenamide, 409. (E)-N-[5-((ydopropylaιmno)-l>3,4-thiadiazol-2-yl]-3-phenyl-2-propenamide,
410. N-[5-(cyclopiOpylammo)-l,3,4-thiadiazol-2-yl]-l-benzothiophene-2- carboxamide,
411. (E)-3-(2-chlorophenyl)-N-{5-[(<:yclopropylmetιhyl)aιmno]-l,3,4-tiήadiazol-2-yl}-2- propenamide, 412. N-{5-[(cyclopropylmeΛyl)ammo]-l,3,4-tWam^ol-2-yl}-2-et-hoxy-l-naphΛamide, 13. (E)-N-{5-[(cyclopropylmethyl)amino]- l,3,4-thiadiazol-2-yl}-9-octadecenamide,
414. N-{5-[((yclopropylmethyl)ammo]-l,3,4-t-hiadiazol-2-yl}-4-iodobenzamide,
415. (E)-3-(2-cMorophenyl)-N-(5-{[2-(m-imidazol-4-yl)etlιyl]amino}-l,3,4-thiadiazol- 2-yl)-2-propenamide, 416. 2-ethoxy-N-(5-{[2-( -inudazol-4-yl)ethyl]aιmno}-l,3,4-thiadiazol-2-yl)-l- naphthamide,
417. (E)-N-(5-{[2-(m-in3idazol-4-yl)ethyl]ammo}-l,3,4-thiadiazol-2-yl)-9- octadecenamide,
418. 2,6-dichloro-N-(5-{[2-( -imidazol-4-yl)ethyl]amino}- l,3,4-thiadiazol-2- yl)benzamide, 419. (E)-N-(5-{[2-( -imidazol-4-yl)ethyl]ammo}-l,3,4-thiadiazol-2-yl)-3-phenyl-2- propenamide,
420. N-(5-{[2-( lH-imidazol-4-yl)ethyl]amino}- l,3,4-thiadiazol-2-yl)-4-iodobenzamide,
421. N-(5-{[2-(m-imidazol-4-yl)ethyl]aπιino}-l,3,4-thiadiazol-2-yl)-2,4,6- triisopropylbenzamide, 422. N-(5-{[2-(m-iπύdazol-4-yl)ethyl]amino}-l,3,4-thiadiazol-2-yl)-l- benzothiophene-2-carboxamide,
423. 4-bromo-N-(5-{[2-(ethykulfanyl)ethyl]ammo}-l,3,4-t^am^ol-2-yl)berιzamide,
424. (E)-3-(2-cWorophenyl)-N-(5-{[2-(ethylsulfany yl)-2-propenamide, 425. 2-eΛoxy-N-(5-{[2-(etιhylsujTanyl)ethyl]ammo}-l,3,4-thiadiazol-2-yl)-l- naphthamide,
426. (E)-N-(5-{[2-(ethylsulfanyl)eΛyl]aιnino}-l,3,4-thiadiazol-2-yl)-9- octadecenamide,
427. 2,6-dicMorc)-N-(5-{[2-(ethylsulfan^^ yDbenzamide,
428. 3,4-diduoro-N-(5-{[2-(eAylsulfanyl)ethyl]amino}-l,3,4-thiadiazol-2- yl)benzamide,
429. N-(5-{[2-(ethylsulfanyl)ethyl]aπ no}-l,3,4-thiadiazol-2-yl)-4- (trifluoromethyl)benzamide, 430. (E)-N-(5-{[2-(ethylsuj anyl)ethyl]ammo}-l,3,4-thiadiazol-2-yl)-3-phenyl-2- propenamide,
431. N-(5-{[2-(etihylsu]fanyl)eΛyl]ammo}-l,3,4-tWadiazol-2-yl)-4-iodobenzaιm
432. N-(5-{[2-(ethylsulfanyl)et l]am^ carboxamide, 433. (E)-3-(2-duorophenyl)-N-[5-(cyclobutylarnino)- l,3,4-thiadiazol-2-yl]-2- propenamide,
434. N-[5-(cyclobutylamino)-l,3,4-thiadiazol-2-yl]-2-ethoxy- 1-naphthamide,
435. (E)-N-[5-(cydobutylamino)- l,3,4-thiadiazol-2-yl]-9-octadecenamide,
436. (E)-N-(5-{[2-(l-me&yl-2-pyrrohclinyl)ethyl]aπ-mo}-l,3,4-thiadiazol-2-yl)-9- octadecenamide,
437. 2,4,6-triisopropyl-N-(5-{[2-( l-methyl-2-pyrrohdmyl)ethyl]amino}- 1,3,4- thiadiazol-2-yl)benzamide,
438. N-[5-(2,3-<i y(lrcHlH-mden-l-ylam o)-l,3,4-t_tø^
439. N-[5-(2,3-(l ydro-lH-mden-l-ylammo)-l,3,4-thiadiazol-2-yl]-2-ethoxy-l- naphthamide, 440. (E)-N-[5-(2,3-d y(iro-m-mden-l-ylamino)-l,3,4-thiadiazol-2-yl]-9- octadecenamide,
441. 2,6-m'cmorcHN-[5-(2,3-dmy<iro- -mden-l-ylammo)-l,3,4-tibiadiazol-2- yl]benzamide,
442. N-[5-(2,3-(l ydro-lH-mden-l-ylaπm o)-l,3,4-tbiam^ol-2-yl]-l,3-dioxc-l,3- di ydro-2-benzofuran-5-carboxamide,
443. N-[5-(2,3-ά^ydro- -mden-l-ylaπι o)-l,3,4-tMam^ol-2-yl]-5-nitro-2- furamide,
444. (E)-3-(2-duorophenyl)-N-[5-(neopentylamino)-l,3,4-thiadiazol-2-yl]-2- propenamide, 445. 2-ethoxy-N-[5-(neopentylammo)-l,3,4-thiadiazol-2-yl]- 1-naphthamide,
446. 2,6-dicUoro-N-[5-(neopentylamino)- l,3,4-thiadiazol-2-yl]benzamide,
447. 2-methoxy-N-t5-(l,2,3,4-tetτahydro-l-naphthalenylaιmno)-l,3,4-ti-iadiazol-2- yl]benzamide,
448. 3-nitro-N-[5-( 1,2,3,4-tetrahydro- 1-naphthalenylamino)- l,3,4-thiadiazol-2- yl]benzamide,
449. 3,5-difluoro-N-[5-( 1,2,3,4-tetrahydro- l-naphΛalenylamino)-l,3,4-thiadiazol-2- yl]benzamide,
450. (E)-3-(2-chlorophenyl)-N-[5-(l,2,3,4-tetrahydro- 1-naphthalenylamino)- 1,3,4- thiadiazol-2-yl]-2-propenamide, 451. 2-ethoxy-N-[5-(l,2,3,4-tetrahydro-l-naphthalenylanuno)-l,3,4-ti-iadiazol-2-yl]- 1-naphthamide,
452. (E)-N-[5-(l,2,3,4-tetxahydro-l-naphthalenylanmιo)-l,3,4-thiadiazol-2-yl]-9- octadecenamide,
453. 2,6-m'(^oro-N-[5-(l,2,3,4-tetrahydro-l-napht±ιalenylammo)-l,3,4-tm^diazol-2- yl]benzamide,
454. l,3-m^xo-N-[5-(l,2,3,4-tetτahydro-l-naphthalenylammo)-l,3,4-thiadiazol-2-yl]- l,3-dmyclro-2-benzofuran-5-carboxamide,
455. 5-m^o-N-[5-(l>2,3,4-tetτahydro-l-naphthalenylammo)-l,3,4-thiadiazol-2-yl]-2- furamide, 456. N-[5-(l,2,3,4-tetxahy(lrc)-l-naphthalenylammo)-l,3,4-thiadiazol-2-yl]-l- benzothiophene-2-carboxamide,
457. ethyl 4-[(5-{[(E)-3-(2-cMorophenyl)-2-propenoyl]amino}- l,3,4-thiadiazol-2- yl)amino]tetrahydro- l(2H)-pyridinecarboxylate,
458. ethyl 4-[(5-{[(2-eΛoxy-l-naphΛyl)carbonyl]arnino}-l,3,4-thiadiazol-2- yl)amino]tetrahydro- l(2H)-pyridinecarboxylate, 459. ethyl 4-({5-[(E)-9-octadecenoylammo]-l,3,4-tm^mazol-2-yl}amino)tetrahydro- l(2H)-pyridinecarboxylate,
460. ethyl 4-({5-t(2,6-di(Worobenzoyl)amino]- l,3,4-thiam^ol-2-yl}amino)tetrahydro- l(2H)-pyridinecarboxylate,
461. ethyl 4-({5-[(l-benzotMophen-2-ylcarbonyl)amino]-l,3,4-thiadiazol-2- yl}aπmιo)tetxahydro-l(2H)-pyridinecarboxylate,
462. N-{5-[(l-benzyl-4-piperidmyl)aπuno]-l,3,4-tihia(U^ol-2-yl}-4-bromobenzamide,
463. (E)-N-{5-[(l-berιzyl-4-piperidmyl)ammo]-l,3,4-thiadiazol-2-yl}-3-(2- chlorophenyl)-2-propenamide,
464. N-{5-[(l-benzyl-4-piperidmyl)amino]-l,3,4-thiadiazol-2-yl}-2-ethoxy-l- naphthamide,
465. (E)-N-{5-[(l-berizyl-4-piperidmyl)amino]-l,3,4-thiadiazol-2-yl}-9- octadecenamide,
466. N-{5-[(l-berιzyl-4-piperidmyl)aιnmo]-l,3,4-thiadiazol-2-yl}-2,6- dichlorobenzamide, 467. (E)-N-{5-[(l-beι zyl-4-piperidmyl)ammo]-l,3,4-thiadiazol-2-yl}-3-phenyl-2- propenamide,
468. N-{5-[( l-benzyl-4-piperidinyl)amino]- l,3,4-thiadiazol-2-yl}-4-iodobenzamide,
469. N-{5-[( l-ber_2yl-4-piperidmyl)amino]- l,3,4-thiadiazol-2-yl}- 1,3-dioxo- l,3-dihydro-2- berιzofuran-5-carboxamide, 470. 4-[({5-[(l-benzyl-4-piperiάmyl)amino]-l,3,4-thiadiazol-2- yl}anuno)carbonyl]benzenesulfonyl fluoride,
471. N-{5-[(l-benzyl-4-piperidmyl)amino]-l,3,4-thiadiazol-2-yl}-2,4,6- triisopropylbenzamide,
472. N-{5-[( l-benzyl-4-piperichnyl)amino]- l,3,4-tMa ^ol-2-yl}-5-m^ro-2-furamide, 473. N-{5-[(l-berιzyl-4-piperi(lmyl)ammo]-l,3,4-tMam^ol-2-yl}-l-benzothiophene-2- carboxamide,
474. (E)-N-(5-{[2-(dimetihylan o)etJιyl]amino}- l,3,4-thiadiazol-2-yl)-9- octadecenamide, or
475. N-(5-{[2-(ά methylanm o)ethyl]amino}- l,3,4-thiadiazol-2-yl)-2,4,6- triisopropylbenzamide.
9. A compound of claim 1 which is
1. N-(5-{[3-(cyclohexylammo)prOpyl]ammo}-l,3,4-tiύadiazol-2-yl)-2-ethoxy-l- naphthamide,
2. N-(5-{[3-(cyclohexylaπιmo)propyl]amino}-l,3,4-thiadiazol-2-yl)-l,3-dioxo-l,3- d ydro-2-benzofuran-5-carboxamide,
3. N-{5-[(3,3-ά phenylpropyl)ammo]-l,3,4-tMam^ol-2-yl}-l,3-dioxc>-l,3-dihydro-2- benzofuran-5-carboxamide,
4. N-{5-[(2,2- phenylethyl)ammo]-l,3,4-tι am^ol-2-yl}-l,3-dioxo-l,3-dihydro-2- beιιzofuran-5-carboxamide, 5. l,3- ^xo-N-[5-(undecylammo)-l,3,4-tMam^ol-2-yl]-l,3-dmy(iro-2-benzofuran- 5-carboxamide,
6. N-[5-({[(2R)-6,6-(limethylbicyclo[3.1. l]hep^2-yl]met_hyl}amino)- 1,3,4-thiadiazol- 2-yl]- 1,3-dioxo- l,3-(lmy(lro-2-berιzofuran-5-carboxamide,
7. l,3-mrøo-N-{5-[(4-phenylbutyl)ammo]-l,3,4-thiam^ol-2-yl}-l,3-dihydro-2- benzofuran-5-carboxamide,
8. N-(5-{[2-( -mdol-3-yl)etiιyl]ammo}-l,3,4-tbiadiazol-2-yl)-l,3-dioxchl,3-dihydro-2- benzofuran-5-carboxamide,
9. (E)-N-(5-{[3-(cyclohexylammo)propyl]anxino}-l,3,4-thiadiazol-2-yl)-9- octadecenamide, 10. 2-etiιoxy-N-(5-{[2-(m-mdol-3-yl)eΛyl]amino}-l,3,4-thiadiazol-2-yl)-l- naphthamide,
11. 2,6-dicMoro-N-(5-{[3-(cyclohexylammo)propyl]amino}-l,3,4-thiadiazol-2- yl)benzamide,
12. N-[5-(cycloheptylamino)- l,3,4-thiadiazol-2-yl]-2-ethoxy- 1-naphthamide, 13. N-[5-({[(2R)-6,6-dimethylbicydo[3.1. l]hept-2-yl]methyl}amino)- 1,3,4-thiadiazol- 2-yl]-2-ethoxy- 1-naphthamide,
14. (E)-N-(5-{[4-(ar nosulfonyl)benzyl]a octadecenamide,
15. N-{5-[(2,2-ά phenylet-hyl)am o]-l,3,4-thiadiazol-2-yl}-2-ethoxy- 1-naphthamide, 16. (E)-N-(5-{[3-(<yclohexylaπι o)propyl]amino}- l,3,4-thiadiazol-2-yl)-3-phenyl-2- propenamide,
17. 2,6-m"cMoro-N-{5-[(3)3-diphenylpropyl)ammo]-l,3,4-thiadiazol-2-yl}benzamide,
18. 2,6-dicMoro-N-{5-[(2,2-diphenylethyl)aπm o]-l,3,4-tMadi^ol-2-yl}benzamide,
19. (E)-N-{5-[(l,3-benzodioxol-5-ylmet-hyl)ammo]-l,3,4-thiadiazol-2-yl}-9- octadecenamide,
20. N-(5-{[4-(aιιunosulfonyl)beιιzyl]ammo}-l,3,4-tMadiazol-2-yl)-2,6- dichlorobenzamide,
21. 2,6-(fi(Moro-N-(5-{[2-( -mdol-3-yl)ethyl]ammo}-l,3,4-tiuadiazol-2- yl)benzamide,
22. 4-cyano-N-{5-[(2,2-m^henylethyl)amiιιo]- l,3,4-thiadiazol-2-yl}benzamide, 23. N-{5-[( l,3-berιzodioxol-5-ylmetiιyl)amino]- l,3,4-thiadiazol-2-yl}- 1,3-dioxo- 1,3- dihydrc-2-benzofuran-5-carboxamide,
24. 4-cyano-N-(5-{[3-(cydohexylaιmno)propyl]amino}-l,3,4-thiadiazol-2- yl)benzamide,
25. N-(5-{[2-( -mdol-3-yl)etlιyl3amino}- l,3,4-tωa ^ol-2-yl)-5-mtτo-2-furamide, 26. 2,6-dichloro-N-[5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept-2-yl]methyl}amino)- l,3,4-thiadiazol-2-yl]benzamide, 27. 4-(yano-N-(5-{[2-(lH-mdol-3-yl)etiιyl]ammo}-l,3,4-t a ^ol-2-yl)benzamide, 28 N-[5-(cycloheptylammo)-l,3,4-t am^ol-2-yl]-l,3-dioxc)-l,3-dihydro-2- benzofuran-5-carboxamide, 29. N-{5-[(l,3-beriZom∞ol-5-ylmethyl)an mo]-l,3,4-thiadiazol-2-yl}-2,6- dichlorobenz amide,
30. N-{5-[(2,2-(fiphenylethyl)ammo]-l,3,4-t^am^ol-2-yl}-2-meώoxybeιιzamide,
31. (E)-N-(5-{[4-(ammosulfonyl)benzyl]amino}- l,3,4-thiadiazol-2-yl)-3-phenyl-2- propenamide, 32. (E)-N-[5-({[(2R)-6,6-dimet_hylbicyclo[3.1.1]hept-2-yl]metiιyl}aπuno)- 1,3,4- thiadiazol-2-yl]-9-octadecenamide,
33. (E)-N-(5-{[2-( -mdol-3-yl)etιhyl]amino}-l,3,4-thiadiazol-2-yl)-9- octadecenamide,
34. (E)-N-[5-(cycloheptylamino)- l,3,4-thiadiazol-2-yl]-9-octadecenamide, 35. (E)-N-{5-[(4-fluorobenzyl)ammo]-l,3,4-tiιiadiazol-2-yl}-9-octadecenamide,
36. 2,6-(ficUoro-N-{5-[(4-phenylbutyl)aπιmo]-l,3,4-tMadiazol-2-yl}beιιzaπu^e, or
37. N-(5-{[4-(ammosuuOnyl)benzyl]ammo}-l,3,4-tMadiazol-2-yl)-2-ethoxy-l- naphthamide.
10. A compound of claim 1 which is
1. N-(5-{[3-((yclohexylammo)propyl]aπ± o}-l,3,4-thiadiazol-2-yl)-2-ethoxy-l- naphthamide,
2. N-(5-{[3-(cydohexylammo)propyl]an ιo}-l,3,4-thiadiazol-2-yl)-l,3-dioxo-l,3- d ydrc-2-benzofuran-5-carboxamide, 3. N-{5-[(3,3-mphenylpropyl)ammo]-l,3,4-t adiazol-2-yl}-l,3-dioxo-l,3-dihydro-2- benzofuran-5-carboxamide,
4. N-{5-[(2,2-mphenylethyl)aπuno]-l,3,4-thiao azol-2-yl}-l,3-dioxo-l,3-dmy(iro-2- berLZofuran-5-carboxamide,
5. l,3-d oxo-N-[5-(undeylammo)-l,3,4-tMa ,azol-2-yl]-l,3-d y(ko-2-benzofuran- 5-carboxamide, 6. N-[5-({[(2R)-6,6-dimethylbicyclo[3.1. l]hept 2-yl]methyl}amino)-l,3,4-thiadiazol- 2-yl]- 1,3-dioxo- l,3-ά ιydro-2-beιιzofuran-5-carboxamide,
7. l,3-(uoxo-N-{5-[(4-phenylbutyl)aπm o]-l,3,4-t_mam^ol-2-yl}-l,3-d ydro-2- benzofuran-5-carboxamide,
8. N-(5-{[2-(m-mdol-3-yl)ethyl]anιino}-l,3,4-thiadiazol-2-yl)- 1,3-dioxo- l,3-dihydro-2- bejazofuran-5-carboxamide, or
9. (E)-N-(5-{[3-((yclohexylan_uno)propyl]amino}- l,3,4-thiadiazol-2-yl)-9- octadecenamide.
11. A pharmaceutical composition which comprises an effective amount of the compound of claim 1 to treat cytomegalovirus infection and a pharmaceutically acceptable carrier.
12. A method for treating viral infections in a mammal comprising administering to said mammal in need thereof an effective amount of a compound of formula I of daim 1.
13. A method of claim 12 wherein said effective amount of a compound of formula is adπiinistered orally, parenterally or topically in a pharmaceutical composition.
14. A method of claim 12 wherein said viral infection is human cytomegalovirus infection.
15. A method of claim 12 wherein said effective amount of a compound of formula is adininistered in an amount of from about 0.1 to 300 mg/kg of mammal body weight.
PCT/US1999/003744 1998-03-19 1999-03-16 1,3,4-thiadiazoles useful for the treatment of cmv infections Ceased WO1999047507A2 (en)

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WO1999047507A3 (en) 1999-12-09
AU743489B2 (en) 2002-01-24
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US6150385A (en) 2000-11-21
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