ES2213775T3 - Metodos de lucha contra las enfermedades infecciosas utilizando bis-benzimidazol dicationicos. - Google Patents

Metodos de lucha contra las enfermedades infecciosas utilizando bis-benzimidazol dicationicos.

Info

Publication number: ES2213775T3
Authority: ES; Spain
Prior art keywords: bis; compound; alkyl; pyridine; compounds
Prior art date: 1995-06-07
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

ES96916817T

Other languages

English (en)

Spanish (es)

Inventor

Christine C. Dykstra

John R. Perfect

David W. Boykin

W. David Wilson

Richard R. Tidwell

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

University of North Carolina at Chapel Hill

Georgia State University Research Foundation Inc

Duke University

Original Assignee

University of North Carolina at Chapel Hill

Georgia State University Research Foundation Inc

Duke University

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1995-06-07

Filing date

1996-06-03

Publication date

2004-09-01

1996-06-03 Application filed by University of North Carolina at Chapel Hill, Georgia State University Research Foundation Inc, Duke University filed Critical University of North Carolina at Chapel Hill

2004-09-01 Application granted granted Critical

2004-09-01 Publication of ES2213775T3 publication Critical patent/ES2213775T3/es

2016-06-03 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

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ADBIDLGZBNZQMZ-UHFFFAOYSA-N 6-(1,4,5,6-tetrahydropyrimidin-2-yl)-2-[6-[6-(1,4,5,6-tetrahydropyrimidin-2-yl)-1h-benzimidazol-2-yl]pyridin-2-yl]-1h-benzimidazole Chemical compound C1CCNC(C=2C=C3NC(=NC3=CC=2)C=2N=C(C=CC=2)C=2NC3=CC(=CC=C3N=2)C=2NCCCN=2)=N1 ADBIDLGZBNZQMZ-UHFFFAOYSA-N 0.000 claims description 6
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125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
235000011083 sodium citrates Nutrition 0.000 description 1
239000000176 sodium gluconate Substances 0.000 description 1
235000012207 sodium gluconate Nutrition 0.000 description 1
229940005574 sodium gluconate Drugs 0.000 description 1
239000001540 sodium lactate Substances 0.000 description 1
229940005581 sodium lactate Drugs 0.000 description 1
235000011088 sodium lactate Nutrition 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
235000011008 sodium phosphates Nutrition 0.000 description 1
235000010339 sodium tetraborate Nutrition 0.000 description 1
238000000527 sonication Methods 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000012360 testing method Methods 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000001149 thermolysis Methods 0.000 description 1
210000001541 thymus gland Anatomy 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
230000036642 wellbeing Effects 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- 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
- A61P31/04—Antibacterial agents
- 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
- A61P31/10—Antimycotics

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Chemical & Material Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

ES96916817T 1995-06-07 1996-06-03 Metodos de lucha contra las enfermedades infecciosas utilizando bis-benzimidazol dicationicos. Expired - Lifetime ES2213775T3 (es)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US08/472,996 US5643935A (en)	1995-06-07	1995-06-07	Method of combatting infectious diseases using dicationic bis-benzimidazoles
US472996		1995-06-07

Publications (1)

Publication Number	Publication Date
ES2213775T3 true ES2213775T3 (es)	2004-09-01

Family

ID=23877744

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ES96916817T Expired - Lifetime ES2213775T3 (es)	1995-06-07	1996-06-03	Metodos de lucha contra las enfermedades infecciosas utilizando bis-benzimidazol dicationicos.

Country Status (9)

Country	Link
US (11)	US5643935A (2)
EP (1)	EP0831832B1 (2)
JP (1)	JPH11507036A (2)
AT (1)	ATE256464T1 (2)
AU (1)	AU705261B2 (2)
CA (1)	CA2223912A1 (2)
DE (1)	DE69631134T2 (2)
ES (1)	ES2213775T3 (2)
WO (1)	WO1996040145A1 (2)

Families Citing this family (47)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5770617A (en) *	1996-03-20	1998-06-23	Rutgers, The State University Of New Jersey	Terbenzimidazoles useful as antifungal agents
US5935982A (en) *	1997-02-28	1999-08-10	The University Of North Carolina At Chapel Hill	Methods of treating retroviral infection and compounds useful therefor
US6635668B1 (en) *	1998-07-22	2003-10-21	The University Of North Carolina At Chapel Hill	Imidazoline receptor binding compounds
JP2002524503A (ja)	1998-09-17	2002-08-06	ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル	二陽イオン分子の抗真菌活性
EP1685836A3 (en) *	1998-09-17	2007-05-09	University Of North Carolina At Chapel Hill	Antifungal activity of dicationic molecules
DE60042921D1 (de) *	1999-03-29	2009-10-22	Shire Canada Inc	Verwendung von cytidinderivaten zur behandlung von leukämie
DK1231910T3 (da) *	1999-11-16	2009-08-31	Oncozyme Pharma Inc	Pentamidin til behandling af cancer
US7115665B1 (en)	2000-11-16	2006-10-03	Onocozyme Pharma, Inc.	Inhibitors of endo-exonuclease activity for treating cancer
US7156809B2 (en)	1999-12-17	2007-01-02	Q-Tec Systems Llc	Method and apparatus for health and disease management combining patient data monitoring with wireless internet connectivity
US6677377B2 (en) *	2000-06-21	2004-01-13	Georgetown University School Of Medicine	Structure based discovery of inhibitors of matriptase for the treatment of cancer and other conditions
US6569853B1 (en) *	2000-11-06	2003-05-27	Combinatorx, Incorporated	Combinations of chlorpromazine and pentamidine for the treatment of neoplastic disorders
US6706754B2 (en) *	2000-11-06	2004-03-16	The United States Of America As Represented By The Secretary Of The Army	Reversed amidines and methods of using for treating, preventing, or inhibiting leishmaniasis
US20040006092A1 (en) *	2001-08-31	2004-01-08	Neurochem, Inc.	Amidine derivatives for treating amyloidosis
US6951880B2 (en)	2002-05-16	2005-10-04	Genelabs Technologies, Inc.	Aryl and heteroaryl compounds as antibacterial and antifungal agents
AU2003245442B2 (en) *	2002-06-13	2009-02-05	Vertex Pharmaceuticals Incorporated	2-ureido-6-heteroaryl-3h-benzoimidazole-4-carboxylic acid derivatives and related compounds as gyrase and/or topoisomerase IV inhibitors for the treatment of bacterial infections
US7569591B2 (en) *	2003-01-31	2009-08-04	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
US7618974B2 (en) *	2003-01-31	2009-11-17	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
US8193352B2 (en) *	2003-01-31	2012-06-05	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
US7582641B2 (en) *	2003-01-31	2009-09-01	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
AR042956A1 (es) *	2003-01-31	2005-07-13	Vertex Pharma	Inhibidores de girasa y usos de los mismos
US8404852B2 (en)	2003-01-31	2013-03-26	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
US20050054708A1 (en) *	2003-07-28	2005-03-10	Nichols Matthew James	Combinations of drugs for the treatment of neoplasms
US20050080075A1 (en) *	2003-08-25	2005-04-14	Nichols M. James	Formulations, conjugates, and combinations of drugs for the treatment of neoplasms
US20050158320A1 (en) *	2003-11-12	2005-07-21	Nichols M. J.	Combinations for the treatment of proliferative diseases
US20050100508A1 (en) *	2003-11-12	2005-05-12	Nichols M. J.	Methods for identifying drug combinations for the treatment of proliferative diseases
US7262223B2 (en) *	2004-01-23	2007-08-28	Neurochem (International) Limited	Amidine derivatives for treating amyloidosis
US7967605B2 (en)	2004-03-16	2011-06-28	Guidance Endodontics, Llc	Endodontic files and obturator devices and methods of manufacturing same
AU2005233632A1 (en)	2004-04-13	2005-10-27	Icagen, Inc.	Polycyclic pyridines as potassium ion channel modulators
DE102004031656A1 (de) *	2004-06-30	2006-01-19	Merck Patent Gmbh	Tetrahydrochinoline
US7817792B2 (en) *	2006-05-04	2010-10-19	Microsoft Corporation	Hyperlink-based softphone call and management
DE102007013854A1 (de)	2007-03-20	2008-09-25	Merck Patent Gmbh	Tetrahydrochinoline
DE102007013856A1 (de)	2007-03-20	2008-09-25	Merck Patent Gmbh	Substituierte Tetrahydropyrrolochinoline
DE102007013855A1 (de)	2007-03-20	2008-09-25	Merck Patent Gmbh	Substituierte Tetrahydrochinoline
EP2194981B1 (en) *	2007-10-05	2011-11-23	Université de Mons-Hainaut	Bisbenzimidazoles as antimalarial agents
WO2010132684A2 (en) *	2009-05-13	2010-11-18	University Of Virginia Patent Foundation	Inhibitors of inv(16) leukemia
JP6085829B2 (ja)	2011-01-14	2017-03-01	スペロトリネム，インコーポレイテッド	ピリミジンジャイレースおよびトポイソメラーゼｉｖ阻害剤
MX341342B (es)	2011-01-14	2016-08-17	Vertex Pharma	Formas solidas del inhibidor de girasa (r)-1-etil-3-[6-fluoro-5-[2 -(1-hidroxi-1-metil-etil) pirimidin-5-il]-7-(tetrahidrofuran-2-il) -1h-benzimidazol-2-il]urea.
US8481552B2 (en)	2011-01-14	2013-07-09	Vertex Pharmaceuticals Incorporated	Solid forms of gyrase inhibitor (R)-1-ethyl-3-[5-[2-(1-hydroxy-1-methyl-ethyl)pyrimidin-5-YL]-7-(tetrahydrofuran-2-yl)-1H-benzimidazol-2-YL]urea
KR101882172B1 (ko)	2011-01-14	2018-07-26	스페로 트리넴, 인코포레이티드	자이라제 및 토포이소머라제 ⅳ 억제제의 제조방법
ES2576298T3 (es)	2011-06-20	2016-07-06	Vertex Pharmaceuticals Incorporated	Ésteres de fosfato de inhibidores de girasa y topoisomerasa
US9018216B2 (en)	2012-07-18	2015-04-28	Vertex Pharmaceuticals Incorporated	Solid forms of (R)-2-(5-(2-(3-ethylureido)-6-fluoro-7-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazol-5-yl)pyrimidin-2-yl)propan-2-yl dihydrogen phosphate and salts thereof
US9572809B2 (en)	2012-07-18	2017-02-21	Spero Trinem, Inc.	Combination therapy to treat Mycobacterium diseases
GB201506658D0 (en)	2015-04-20	2015-06-03	Cellcentric Ltd	Pharmaceutical compounds
GB201506660D0 (en)	2015-04-20	2015-06-03	Cellcentric Ltd	Pharmaceutical compounds
MX2017014613A (es) *	2015-05-15	2018-03-01	Gilead Sciences Inc	Compuestos de bencimidazol e imadazopiridin-carboximidamida que tienen actividad como inhibidores de indolamina 2,3-dioxigenasa.
MX2019000179A (es) *	2016-07-27	2019-06-20	Univ Virginia Patent Foundation	Combinacion de terapias para tratar el cancer.
US20200030295A1 (en) *	2016-08-02	2020-01-30	Friedrich-Alexander-Universität Erlangen-Nürnberg	Heterocyclic diamidines

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1542284A (en) *	1976-01-09	1979-03-14	Barcrest Ltd	Recording electrical information
ES467739A1 (es) *	1977-03-16	1979-07-01	Hoechst Ag	Procedimiento para la preparacion de compuestos de bisbenci-midazolil sustituidos
DE2839989A1 (de) *	1978-09-14	1980-04-03	Hoechst Ag	Substituierte bisbenzimidazolylverbindungen, ihre herstellung und ihre verwendung
US4933347A (en) *	1988-10-25	1990-06-12	University Of North Carolina At Chapel Hill	Diamidines and bis(imidazolines) for the treatment of and prophylaxis against pneumocystis carinii pneumonia
US4963589A (en) *	1988-10-25	1990-10-16	The University Of North Carolina At Chapel Hill	Methods for treating Giardia lamblia
US5134152A (en) *	1989-12-07	1992-07-28	Sankyo Company, Limited	Oxetane derivatives and their use as anti-fungal or fungicidal agents
FR2674246B1 (fr) *	1991-03-21	1993-07-09	Roussel Uclaf	Nouveaux derives de l'acide alpha-methylene 5-thiazolacetique, leur procede de preparation et les intermediaires de ce procede, leur application a titre de fongicides et les compositions les renfermant.
EP0508527A1 (en) *	1991-04-11	1992-10-14	UNIROYAL CHEMICAL COMPANY, Inc.	New fungicidally active pyrazole compounds
US5362910A (en) *	1991-10-08	1994-11-08	Nicca Chemical Co., Ltd.	Germicidal and fungicidal agent and a germicidal and fungicidal method
JPH05140114A (ja) *	1991-11-22	1993-06-08	Otsuka Chem Co Ltd	アゾール−１−カルボン酸エステル誘導体及び殺菌剤
US5428051A (en) *	1992-10-13	1995-06-27	University Of North Carolina	Methods of combating pneumocystis carinii pneumonia and compounds useful therefor
US5667975A (en) *	1994-05-06	1997-09-16	The University Of North Carolina	Method of fluorescent detection of nucleic acids and cytoskeleton elements using bis-dicationic aryl furans

1995
- 1995-06-07 US US08/472,996 patent/US5643935A/en not_active Expired - Fee Related
1996
- 1996-05-01 US US08/641,510 patent/US5639755A/en not_active Expired - Fee Related
- 1996-06-03 EP EP96916817A patent/EP0831832B1/en not_active Expired - Lifetime
- 1996-06-03 DE DE69631134T patent/DE69631134T2/de not_active Expired - Fee Related
- 1996-06-03 AU AU59566/96A patent/AU705261B2/en not_active Ceased
- 1996-06-03 JP JP9500868A patent/JPH11507036A/ja not_active Ceased
- 1996-06-03 CA CA002223912A patent/CA2223912A1/en not_active Abandoned
- 1996-06-03 WO PCT/US1996/008084 patent/WO1996040145A1/en not_active Ceased
- 1996-06-03 ES ES96916817T patent/ES2213775T3/es not_active Expired - Lifetime
- 1996-06-03 AT AT96916817T patent/ATE256464T1/de not_active IP Right Cessation
1997
- 1997-05-29 US US08/865,424 patent/US5792782A/en not_active Expired - Lifetime
- 1997-05-29 US US08/865,425 patent/US5817687A/en not_active Expired - Fee Related
- 1997-05-29 US US08/865,427 patent/US5817686A/en not_active Expired - Fee Related
1998
- 1998-08-07 US US09/130,496 patent/US5939440A/en not_active Expired - Fee Related
- 1998-09-01 US US09/145,367 patent/US5972969A/en not_active Expired - Lifetime
- 1998-09-01 US US09/145,368 patent/US6017941A/en not_active Expired - Lifetime
1999
- 1999-07-13 US US09/352,391 patent/US6046226A/en not_active Expired - Lifetime
2000
- 2000-01-04 US US09/477,386 patent/US6156779A/en not_active Expired - Lifetime
- 2000-04-06 US US09/544,643 patent/US6294565B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
US5817686A (en)	1998-10-06
WO1996040145A1 (en)	1996-12-19
AU5956696A (en)	1996-12-30
EP0831832A4 (en)	1999-07-07
CA2223912A1 (en)	1996-12-19
US5939440A (en)	1999-08-17
US5643935A (en)	1997-07-01
US5792782A (en)	1998-08-11
AU705261B2 (en)	1999-05-20
US6046226A (en)	2000-04-04
US6017941A (en)	2000-01-25
EP0831832B1 (en)	2003-12-17
DE69631134D1 (de)	2004-01-29
US5639755A (en)	1997-06-17
JPH11507036A (ja)	1999-06-22
US6156779A (en)	2000-12-05
US5817687A (en)	1998-10-06
DE69631134T2 (de)	2004-09-02
US5972969A (en)	1999-10-26
EP0831832A1 (en)	1998-04-01
US6294565B1 (en)	2001-09-25
ATE256464T1 (de)	2004-01-15

Publication	Publication Date	Title
EP0831832B1 (en)	2003-12-17	Methods of combatting infectious diseases using dicationic bis-benzimidazoles
US5627184A (en)	1997-05-06	Methods of treating Giardia lamblia
EP1143959B1 (en)	2006-11-02	Antifungal activity of dicationic molecules
KR102232625B1 (ko)	2021-03-25	폐 병태의 치료를 위한 고침투 전구약물 조성물 및 그의 약제학적 조성물
AU2021201251B2 (en)	2022-07-21	Antimicrobial compounds, compositions, and uses thereof
JP2011500577A (ja)	2011-01-06	バルサルタンの医薬製剤
ES2236734T3 (es)	2005-07-16	Metodos para combatir la neumonia pneumocystis carinii y compuestos utiles para ello.
JP3306830B2 (ja)	2002-07-24	レトロウイルスインテグラーゼの阻害剤
HUP0203121A2 (hu)	2003-01-28	Szubsztituált benzimidazolokat tartalmazó gyógyszerkészítmény és alkalmazása
JP4823894B2 (ja)	2011-11-24	新規水溶性プロドラッグ
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EP0792271B1 (en)	2002-02-27	Furan derivatives for inhibiting pneumocystis carinii pneumonia, giardia lamblia and cryptosporidium parvum
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US20070281947A1 (en)	2007-12-06	Diarylmethylpiperazines As Prophylactic Or Therapeutic Agents For Viral Myocarditis
US20030216324A1 (en)	2003-11-20	Airway mucus secretion inhibitors
KR20000035863A (ko)	2000-06-26	Ｈｉｖ 감염과 관련된 중추 신경계 질환 치료용 약제를 제조하기 위해 ｐｋｃ의 억제제를 사용하는 방법