JPH11507036A - ジカチオン性ビス−ベンズイミダゾール類を用いた感染病治療方法 - Google Patents

ジカチオン性ビス−ベンズイミダゾール類を用いた感染病治療方法

Info

Publication number: JPH11507036A
Authority: JP; Japan
Prior art keywords: bis; benzimidazolyl; structural formula; following structural; lower alkyl
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.): Ceased

Application number

JP9500868A

Other languages

English (en)

Japanese (ja)

Other versions

JPH11507036A5 (2

Inventor

ダイクストラ，クリスティン・シー

パーフェクト，ジョン・アール

ボイキン，デイヴィッド・ダブリュー

ウィルソン，ダブリュー・デイヴィッド

ティドウェル，リチャード・アール

Original Assignee

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

デューク・ユニヴァーシティ

ジョージア・ステイト・ユニヴァーシティ・リサーチ・ファンデイション，インコーポレイテッド

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

1999-06-22

1996-06-03 Application filed by 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, デューク・ユニヴァーシティ, ジョージア・ステイト・ユニヴァーシティ・リサーチ・ファンデイション，インコーポレイテッド filed Critical 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

1999-06-22 Publication of JPH11507036A publication Critical patent/JPH11507036A/ja

2004-07-22 Publication of JPH11507036A5 publication Critical patent/JPH11507036A5/ja

Status Ceased legal-status Critical Current

Links

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Classifications

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

JP9500868A 1995-06-07 1996-06-03 ジカチオン性ビス−ベンズイミダゾール類を用いた感染病治療方法 Ceased JPH11507036A (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US08/472,996		1995-06-07
US08/472,996 US5643935A (en)	1995-06-07	1995-06-07	Method of combatting infectious diseases using dicationic bis-benzimidazoles
PCT/US1996/008084 WO1996040145A1 (en)	1995-06-07	1996-06-03	Methods of combatting infectious diseases using dicationic bis-benzimidazoles

Publications (2)

Publication Number	Publication Date
JPH11507036A true JPH11507036A (ja)	1999-06-22
JPH11507036A5 JPH11507036A5 (2)	2004-07-22

Family

ID=23877744

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP9500868A Ceased JPH11507036A (ja)	1995-06-07	1996-06-03	ジカチオン性ビス−ベンズイミダゾール類を用いた感染病治療方法

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
EP1685836A3 (en) *	1998-09-17	2007-05-09	University Of North Carolina At Chapel Hill	Antifungal activity of dicationic molecules
DE69933890T2 (de) *	1998-09-17	2007-03-15	University Of North Carolina At Chapel Hill	Antimykotische wirkung von dikationischen molekülen
KR20050005569A (ko) *	1999-03-29	2005-01-13	샤이어 바이오켐 인코포레이티드	백혈병 치료방법
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
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
US6569853B1 (en) *	2000-11-06	2003-05-27	Combinatorx, Incorporated	Combinations of chlorpromazine and pentamidine for the treatment of neoplastic disorders
IL160208A0 (en) *	2001-08-31	2004-07-25	Neurochem Int Ltd	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
DE60309701T2 (de) *	2002-06-13	2007-09-06	Vertex Pharmaceuticals Inc., Cambridge	2-ureido-6-heteroaryl-3h-benzoimidazol-4-carbonsäurederivate und verwandte verbindungen als gyrase und/oder topoisomerase iv inhibitoren zur behandlung von bakteriellen infektionen
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
US8193352B2 (en) *	2003-01-31	2012-06-05	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
US7618974B2 (en) *	2003-01-31	2009-11-17	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
US7569591B2 (en) *	2003-01-31	2009-08-04	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
US7582641B2 (en) *	2003-01-31	2009-09-01	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
AR047938A1 (es) *	2003-08-25	2006-03-15	Combinatorx Inc	Formulaciones, conjugados y combinaciones de farmacos para el tratamiento de neoplasmas
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
EP1742936A2 (en) *	2004-04-13	2007-01-17	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
DE102007013855A1 (de)	2007-03-20	2008-09-25	Merck Patent Gmbh	Substituierte Tetrahydrochinoline
DE102007013856A1 (de)	2007-03-20	2008-09-25	Merck Patent Gmbh	Substituierte Tetrahydropyrrolochinoline
DE102007013854A1 (de)	2007-03-20	2008-09-25	Merck Patent Gmbh	Tetrahydrochinoline
EP2194981B1 (en) *	2007-10-05	2011-11-23	Université de Mons-Hainaut	Bisbenzimidazoles as antimalarial agents
EP3670509B1 (en) *	2009-05-13	2023-04-19	University of Virginia Patent Foundation	Inhibitors of inv(16) leukemia
CN103384665B (zh)	2011-01-14	2018-01-09	斯派罗吹耐姆公司	制备促旋酶和拓扑异构酶抑制剂的方法
US8476281B2 (en)	2011-01-14	2013-07-02	Vertex Pharmaceuticals Incorporated	Solid forms of gyrase inhibitor (R)-1-ethyl-3-[6-fluoro-5-[2-(1-hydroxy-1-methyl-ethyl)pyrimidin-5-yl]-7-(tetrahydrofuran-2-yl)-1H-benzimidazol-2-yl]urea
AU2012205415B2 (en)	2011-01-14	2017-02-02	Spero Therapeutics, Inc.	Pyrimidine gyrase and topoisomerase IV inhibitors
WO2012097270A1 (en)	2011-01-14	2012-07-19	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
CN103702994B (zh)	2011-06-20	2016-03-23	沃泰克斯药物股份有限公司	旋转酶和拓扑异构酶抑制剂的磷酸酯
US9572809B2 (en)	2012-07-18	2017-02-21	Spero Trinem, Inc.	Combination therapy to treat Mycobacterium diseases
WO2014015105A1 (en)	2012-07-18	2014-01-23	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
GB201506658D0 (en)	2015-04-20	2015-06-03	Cellcentric Ltd	Pharmaceutical compounds
GB201506660D0 (en)	2015-04-20	2015-06-03	Cellcentric Ltd	Pharmaceutical compounds
BR112017024331A2 (pt) *	2015-05-15	2018-07-24	Gilead Sciences, Inc.	composto, composição farmacêutica, método de tratamento de um humano, métodos para inibir a atividade de uma proteína ido1, o crescimento ou a proliferação de células cancerosas, e a imunossupressão em um paciente, e de tratamento de uma doença, e, uso de um composto
CA3028461A1 (en)	2016-07-27	2018-02-01	University Of Virginia Patent Foundation	Combination therapies for treating cancer
WO2018024654A1 (en) *	2016-08-02	2018-02-08	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 AU AU59566/96A patent/AU705261B2/en not_active Ceased
- 1996-06-03 ES ES96916817T patent/ES2213775T3/es not_active Expired - Lifetime
- 1996-06-03 EP EP96916817A patent/EP0831832B1/en not_active Expired - Lifetime
- 1996-06-03 AT AT96916817T patent/ATE256464T1/de not_active IP Right Cessation
- 1996-06-03 CA CA002223912A patent/CA2223912A1/en not_active Abandoned
- 1996-06-03 JP JP9500868A patent/JPH11507036A/ja not_active Ceased
- 1996-06-03 WO PCT/US1996/008084 patent/WO1996040145A1/en not_active Ceased
- 1996-06-03 DE DE69631134T patent/DE69631134T2/de not_active Expired - Fee Related
1997
- 1997-05-29 US US08/865,425 patent/US5817687A/en not_active Expired - Fee Related
- 1997-05-29 US US08/865,424 patent/US5792782A/en not_active Expired - Lifetime
- 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
US5792782A (en)	1998-08-11
US5939440A (en)	1999-08-17
DE69631134D1 (de)	2004-01-29
US5643935A (en)	1997-07-01
EP0831832B1 (en)	2003-12-17
US5817687A (en)	1998-10-06
DE69631134T2 (de)	2004-09-02
US5817686A (en)	1998-10-06
AU705261B2 (en)	1999-05-20
AU5956696A (en)	1996-12-30
ES2213775T3 (es)	2004-09-01
CA2223912A1 (en)	1996-12-19
US6017941A (en)	2000-01-25
EP0831832A4 (en)	1999-07-07
EP0831832A1 (en)	1998-04-01
WO1996040145A1 (en)	1996-12-19
ATE256464T1 (de)	2004-01-15
US5972969A (en)	1999-10-26
US5639755A (en)	1997-06-17
US6294565B1 (en)	2001-09-25
US6156779A (en)	2000-12-05
US6046226A (en)	2000-04-04

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