AP736A - Benzimidazole derivatives and their use in medical therapy particularly for the treatment of virus infections. - Google Patents

Benzimidazole derivatives and their use in medical therapy particularly for the treatment of virus infections. Download PDF

Info

Publication number: AP736A
Authority: AP; ARIPO
Prior art keywords: compound; formula; mmol; dichloro; alkyl
Prior art date: 1994-07-07

Application number

APAP/P/1996/000895A

Other languages

English (en)

Other versions

AP9600895A0 (en

Inventor

Stanley Dawes Chamberlain

George Walter Koszalka

Original Assignee

The Wellcome Foundation Ltd

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.)

1994-07-07

Filing date

1995-07-06

Publication date

1999-03-09

1995-07-06 Application filed by The Wellcome Foundation Ltd filed Critical The Wellcome Foundation Ltd

1997-01-31 Publication of AP9600895A0 publication Critical patent/AP9600895A0/xx

1999-03-09 Application granted granted Critical

1999-03-09 Publication of AP736A publication Critical patent/AP736A/en

Links

238000011282 treatment Methods 0.000 title claims abstract description 21
230000009385 viral infection Effects 0.000 title claims abstract description 14
229940058303 antinematodal benzimidazole derivative Drugs 0.000 title abstract description 5
238000013160 medical therapy Methods 0.000 title abstract description 4
125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title abstract 3
125000000217 alkyl group Chemical group 0.000 claims abstract description 27
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 22
239000001257 hydrogen Substances 0.000 claims abstract description 20
125000005843 halogen group Chemical group 0.000 claims abstract description 15
125000003118 aryl group Chemical group 0.000 claims abstract description 11
238000011321 prophylaxis Methods 0.000 claims abstract description 9
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 6
238000002360 preparation method Methods 0.000 claims abstract description 6
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 5
150000001875 compounds Chemical class 0.000 claims description 126
239000000203 mixture Substances 0.000 claims description 53
238000009472 formulation Methods 0.000 claims description 32
238000000034 method Methods 0.000 claims description 31
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
239000003795 chemical substances by application Substances 0.000 claims description 19
208000015181 infectious disease Diseases 0.000 claims description 18
-1 isopropyl amino Chemical group 0.000 claims description 16
150000003839 salts Chemical class 0.000 claims description 16
150000002148 esters Chemical class 0.000 claims description 15
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
239000003814 drug Substances 0.000 claims description 11
208000036142 Viral infection Diseases 0.000 claims description 9
241000701085 Human alphaherpesvirus 3 Species 0.000 claims description 8
241000701044 Human gammaherpesvirus 4 Species 0.000 claims description 8
241000701022 Cytomegalovirus Species 0.000 claims description 7
241000700605 Viruses Species 0.000 claims description 7
239000002253 acid Substances 0.000 claims description 7
229940124597 therapeutic agent Drugs 0.000 claims description 7
208000029433 Herpesviridae infectious disease Diseases 0.000 claims description 6
241000701027 Human herpesvirus 6 Species 0.000 claims description 6
241001465754 Metazoa Species 0.000 claims description 6
125000006239 protecting group Chemical group 0.000 claims description 6
125000001627 3 membered heterocyclic group Chemical group 0.000 claims description 5
125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 5
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 5
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 5
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
241000700588 Human alphaherpesvirus 1 Species 0.000 claims description 5
241000701041 Human betaherpesvirus 7 Species 0.000 claims description 5
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
241000701074 Human alphaherpesvirus 2 Species 0.000 claims description 4
150000007513 acids Chemical class 0.000 claims description 4
150000002431 hydrogen Chemical group 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
150000001412 amines Chemical class 0.000 claims description 3
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
125000004429 atom Chemical group 0.000 claims description 3
150000001735 carboxylic acids Chemical class 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 3
230000000694 effects Effects 0.000 claims description 3
230000002140 halogenating effect Effects 0.000 claims description 3
230000002265 prevention Effects 0.000 claims description 3
208000024891 symptom Diseases 0.000 claims description 3
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238000002560 therapeutic procedure Methods 0.000 claims description 2
UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical class OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims description 2
150000001413 amino acids Chemical class 0.000 claims 1
JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
KJFBVJALEQWJBS-XUXIUFHCSA-N maribavir Chemical compound CC(C)NC1=NC2=CC(Cl)=C(Cl)C=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O KJFBVJALEQWJBS-XUXIUFHCSA-N 0.000 claims 1
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims 1
125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 5
241001529453 unidentified herpesvirus Species 0.000 abstract description 4
125000003342 alkenyl group Chemical group 0.000 abstract description 2
125000000623 heterocyclic group Chemical group 0.000 abstract description 2
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 101
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 88
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
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239000007787 solid Substances 0.000 description 53
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 48
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239000012043 crude product Substances 0.000 description 11
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238000006243 chemical reaction Methods 0.000 description 9
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125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
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ILJSQTXMGCGYMG-UHFFFAOYSA-N triacetic acid Chemical compound CC(=O)CC(=O)CC(O)=O ILJSQTXMGCGYMG-UHFFFAOYSA-N 0.000 description 7
FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 7
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
241000282414 Homo sapiens Species 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
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238000000746 purification Methods 0.000 description 5
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239000002904 solvent Substances 0.000 description 5
239000000829 suppository Substances 0.000 description 5
VHBFEIBMZHEWSX-UHFFFAOYSA-N 2-isothiocyanatopropane Chemical compound CC(C)N=C=S VHBFEIBMZHEWSX-UHFFFAOYSA-N 0.000 description 4
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PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
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HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical
- 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
- 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
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/052—Imidazole radicals
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Virology (AREA)
General Health & Medical Sciences (AREA)
Molecular Biology (AREA)
Engineering & Computer Science (AREA)
Biotechnology (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Oncology (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Medicinal Chemistry (AREA)
Communicable Diseases (AREA)
Biochemistry (AREA)
Genetics & Genomics (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)

APAP/P/1996/000895A 1994-07-07 1995-07-06 Benzimidazole derivatives and their use in medical therapy particularly for the treatment of virus infections. AP736A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB9413724A GB9413724D0 (en)	1994-07-07	1994-07-07	Therapeutic nucleosides
PCT/GB1995/001597 WO1996001833A1 (en)	1994-07-07	1995-07-06	Therapeutic compounds

Publications (2)

Publication Number	Publication Date
AP9600895A0 AP9600895A0 (en)	1997-01-31
AP736A true AP736A (en)	1999-03-09

Family

ID=10757983

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
APAP/P/1996/000895A AP736A (en)	1994-07-07	1995-07-06	Benzimidazole derivatives and their use in medical therapy particularly for the treatment of virus infections.

Country Status (43)

Country	Link
US (4)	US6077832A (es)
EP (1)	EP0769017B1 (es)
JP (1)	JP3225045B2 (es)
KR (1)	KR100376075B1 (es)
CN (2)	CN1052010C (es)
AP (1)	AP736A (es)
AT (1)	ATE193298T1 (es)
AU (1)	AU702248B2 (es)
BG (1)	BG63435B1 (es)
BR (1)	BR9508237A (es)
CY (1)	CY2249B1 (es)
CZ (1)	CZ290800B6 (es)
DE (1)	DE69517172T2 (es)
DK (1)	DK0769017T3 (es)
EE (1)	EE03568B1 (es)
ES (1)	ES2147294T3 (es)
FI (1)	FI117629B (es)
GB (1)	GB9413724D0 (es)
GE (1)	GEP20002298B (es)
GR (1)	GR3033744T3 (es)
HR (1)	HRP950382B1 (es)
HU (1)	HU227679B1 (es)
IL (1)	IL114492A (es)
IS (1)	IS1812B (es)
MD (1)	MD1838G2 (es)
MX (1)	MX9606732A (es)
MY (1)	MY117892A (es)
NO (1)	NO308854B1 (es)
NZ (1)	NZ288722A (es)
OA (1)	OA10339A (es)
PL (1)	PL181136B1 (es)
PT (1)	PT769017E (es)
RO (1)	RO117699B1 (es)
RU (1)	RU2145963C1 (es)
SA (1)	SA95160202B1 (es)
SK (1)	SK282046B6 (es)
TJ (1)	TJ270B (es)
TR (1)	TR199500832A2 (es)
TW (1)	TW418196B (es)
UA (1)	UA66744C2 (es)
WO (1)	WO1996001833A1 (es)
YU (1)	YU49443B (es)
ZA (1)	ZA955644B (es)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9413724D0 (en) *	1994-07-07	1994-08-24	Wellcome Found	Therapeutic nucleosides
WO1997007125A1 (en) *	1995-08-18	1997-02-27	The Regents Of The University Of Michigan	5'-substituted-ribofuranosyl benzimidazoles as antiviral agents
GB9518465D0 (en) *	1995-09-09	1995-11-08	Smithkline Beecham Seiyaku Kk	Pharmaceuticals
GB9600142D0 (en) *	1996-01-05	1996-03-06	Wellcome Found	Chemical compounds
GB9600143D0 (en) *	1996-01-05	1996-03-06	Wellcome Found	Therapeutic compounds
US5840743A (en) *	1996-01-23	1998-11-24	The Regents Of The University Of Michigan	Modified benzimidazole nucleosides as antiviral agents
US6475388B1 (en)	1996-11-13	2002-11-05	Transgenomic, Inc.	Method and system for RNA analysis by matched ion polynucleotide chromatography
US6576133B2 (en)	1996-11-13	2003-06-10	Transgenomic, Inc	Method and system for RNA analysis by matched ion polynucleotide chromatography
GB2319961A (en) *	1996-12-07	1998-06-10	Glaxo Group Ltd	Pharmaceutical composition for treatment of restenosis
US6413938B1 (en)	1997-02-13	2002-07-02	The Regents Of The University Of Michigan	Benzimidazole derivatives for the treatment of viral infections
ID24054A (id) *	1997-06-10	2000-07-06	Glaxo Group Ltd Glaxo	Turunan turunan benzimidazol
AU744176B2 (en)	1997-07-30	2002-02-14	Glaxo Group Limited	Lyxofuranosyl benzimidazoles as antiviral agents
US6258264B1 (en)	1998-04-10	2001-07-10	Transgenomic, Inc.	Non-polar media for polynucleotide separations
GB9807355D0 (en) *	1998-04-07	1998-06-03	Glaxo Group Ltd	Antiviral compound
GB9807354D0 (en)	1998-04-07	1998-06-03	Glaxo Group Ltd	Antiviral compound
US6277830B1 (en) *	1998-10-16	2001-08-21	Schering Corporation	5′-amino acid esters of ribavirin and the use of same to treat hepatitis C with interferon
US6576265B1 (en)	1999-12-22	2003-06-10	Acell, Inc.	Tissue regenerative composition, method of making, and method of use thereof
GB0008939D0 (en) *	2000-04-11	2000-05-31	Glaxo Group Ltd	Process for preparing substituted benzimidazole compounds
RU2262344C2 (ru) *	2001-07-25	2005-10-20	Дж.Б.Кемикалс Энд Фармасьютикалс Лтд.	Фармацевтическая композиция для лечения кожных инфекций и способ ее получения
RU2366661C2 (ru) *	2002-06-28	2009-09-10	Айденикс (Кайман) Лимитед	Пролекарства модифицированных 2'- и 3'-нуклеозидов для лечения инфекций flaviviridae
CA2530490A1 (en)	2003-06-25	2005-01-13	Stephen F. Badylak	Conditioned matrix compositions for tissue restoration
WO2005063788A1 (ja) *	2003-12-26	2005-07-14	Kissei Pharmaceutical Co., Ltd.	ベンズイミダゾール誘導体及びその医薬用途
RU2268741C1 (ru) *	2004-08-04	2006-01-27	Государственное образовательное учреждение высшего профессионального образования "Южно-Уральский государственный университет"	Способ лечения герпетического поражения вестибулярного, спирального, тригеминального и коленчатого ганглиев
JPWO2006115137A1 (ja) *	2005-04-22	2008-12-18	キッセイ薬品工業株式会社	２−アミノベンズイミダゾール誘導体及びその医薬用途
EA008737B1 (ru) *	2005-12-07	2007-08-31	Леонид Андреевич Кожемякин	Средство для профилактики и лечения конъюнктивитов и кератитов различной этиологии (варианты), способ его применения
US8541391B2 (en)	2010-10-28	2013-09-24	Viropharma Incorporated	Crystalline phases of 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole
US8940707B2 (en)	2010-10-28	2015-01-27	Viropharma Incorporated	Maribavir isomers, compositions, methods of making and methods of using
US8546344B2 (en)	2010-10-28	2013-10-01	Viropharma Incorporated	Crystalline phases of 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl)-1H-benzimidazole
US9447050B2 (en)	2011-04-05	2016-09-20	The Translational Genomics Research Institute	Solid forms of curcumin
US20140004307A1 (en)	2012-06-29	2014-01-02	The Procter & Gamble Company	Textured Fibrous Webs, Apparatus And Methods For Forming Textured Fibrous Webs
WO2014145852A2 (en)	2013-03-15	2014-09-18	Knopp Biosciences Llc	Imidazo(4,5-b) pyridin-2-yl amides as kv7 channel activators
ES2749103T3 (es)	2014-09-12	2020-03-19	Knopp Biosciences Llc	Benzoimidazol-1,2-ilamidas como activadores del canal Kv7
EP3223816B1 (en) *	2014-11-26	2020-04-22	The J. David Gladstone Institutes	Methods for treating a cytomegalovirus infection
RU2629670C2 (ru) *	2016-08-04	2017-08-31	Федеральное государственное бюджетное учреждение науки институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова Российской академии наук (ИБХ РАН)	2-Амино-5,6-дифтор-1-(бета-D-рибофуранозил)-бензимидазол, способ получения и противовирусная активность его в отношении вируса герпеса простого 1-го типа
CN119118926A (zh)	2018-03-19	2024-12-13	诺普生物科学有限责任公司	Kv7通道激活剂组合物和使用方法
KR102449266B1 (ko) *	2020-06-23	2022-09-30	(주)바이오메트릭스 테크놀로지	항암 활성 그리고 항바이러스 활성을 갖는 신규한 벤지미다졸-탄수화물 결합체 화합물(Benzimidazole carbohydrate conjugate compound) 및 이의 제조 방법
IL319923A (en)	2022-10-12	2025-05-01	Takeda Pharmaceuticals Co	Maribavir preparation method
WO2024103979A1 (zh) *	2022-11-17	2024-05-23	北京凯因科技股份有限公司	一种抑制疱疹病毒的化合物

Citations (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2130030A1 (de) *	1971-06-18	1972-12-21	Bayer Ag	Fungizide und bakterizide Mittel
WO1992007867A1 (en) *	1990-11-01	1992-05-14	The Regents Of The University Of Michigan	Polysubstituted benzimidazoles as antiviral agents
WO1994008456A1 (en) *	1992-10-21	1994-04-28	The Regents Of The University Of Michigan	Polysubstituted benzimidazoles as antiviral agents

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3399987A (en) *	1965-08-02	1968-09-03	United States Borax Chem	2-alkylaminobenzimidazoles as herbicides
CH443777A (de) *	1965-08-06	1968-02-15	Agripat Sa	Verfahren zum Schützen textiler Keratinfasern vor Insektenfrass und Mittel zur Durchführung dieses Verfahrens
NL6716664A (es) *	1966-12-19	1968-06-20
US3655901A (en) *	1970-07-30	1972-04-11	Merck & Co Inc	Method of inhibiting the formation of phenylethanalamine-n-methyl transferase with 2-aminobenzimidazoles
US4002623A (en) *	1974-08-07	1977-01-11	Pfizer Inc.	Anti-inflammatory 1-[3-(dialkylamino)propyl]-2-acylaminobenzimidazoles and 2-acylamino-3-[3-(dialkylamino)-propyl]imidazo[4,5-b]pyridines
FR2549938B1 (fr) *	1983-07-25	1987-08-07	Fonderie Soc Gen De	Bruleur a premelange gazeux et chaudiere equipee d'un tel bruleur
FR2551442B1 (fr) *	1983-09-05	1987-04-30	Centre Nat Rech Scient	Nouveaux derives furaniques, leur preparation et leur application
CH667649A5 (en) *	1986-09-10	1988-10-31	Lonza Ag	2-Substd. amino-benzoxazole and -benzimidazole derivs. prodn. - by reacting prim. amino cpd. with amine in presence of acid catalyst, useful as intermediates e.g. for pharmaceuticals
DK405988A (da) *	1987-07-29	1989-01-30	Hoffmann La Roche	Benzimidazolderivater
IT1226100B (it) *	1988-07-07	1990-12-10	Dompe Farmaceutici Spa	Derivati benzimidazolici farmacologicamente attivi.
DE3924424A1 (de) *	1989-07-24	1991-01-31	Boehringer Mannheim Gmbh	Nucleosid-derivate, verfahren zu deren herstellung, deren verwendung als arzneimittel sowie deren verwendung bei der nucleinsaeure-sequenzierung
SE9003151D0 (sv) *	1990-10-02	1990-10-02	Medivir Ab	Nucleoside derivatives
WO1992018517A1 (en) *	1991-04-17	1992-10-29	Yale University	Method of treating or preventing hepatitis b virus
ZA923641B (en) *	1991-05-21	1993-02-24	Iaf Biochem Int	Processes for the diastereoselective synthesis of nucleosides
ATE138928T1 (de) *	1991-09-04	1996-06-15	Stichting Rega V Z W	Substituierte nukleosidderivate, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische zusammensetzungen
US5314903A (en) *	1991-12-03	1994-05-24	Neurosearch A/S	Benzimidazole compounds useful as calcium channel blockers
GB9205071D0 (en) *	1992-03-09	1992-04-22	Wellcome Found	Therapeutic nucleosides
US5399580A (en) *	1993-03-08	1995-03-21	Burroughs Wellcome Co.	Therapeutic nucleosides-uses
GB9413724D0 (en) *	1994-07-07	1994-08-24	Wellcome Found	Therapeutic nucleosides
JP6217655B2 (ja) *	2015-01-15	2017-10-25	トヨタ自動車株式会社	電力変換装置

1994
- 1994-07-07 GB GB9413724A patent/GB9413724D0/en active Pending
1995
- 1995-07-06 CZ CZ199740A patent/CZ290800B6/cs not_active IP Right Cessation
- 1995-07-06 GE GEAP19953510A patent/GEP20002298B/en unknown
- 1995-07-06 MX MX9606732A patent/MX9606732A/es unknown
- 1995-07-06 BR BR9508237A patent/BR9508237A/pt not_active IP Right Cessation
- 1995-07-06 RU RU97101461A patent/RU2145963C1/ru active
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- 1995-07-06 EP EP95923513A patent/EP0769017B1/en not_active Expired - Lifetime
- 1995-07-06 WO PCT/GB1995/001597 patent/WO1996001833A1/en not_active Ceased
- 1995-07-06 PL PL95318062A patent/PL181136B1/pl unknown
- 1995-07-06 AU AU28051/95A patent/AU702248B2/en not_active Expired
- 1995-07-06 DK DK95923513T patent/DK0769017T3/da active
- 1995-07-06 AP APAP/P/1996/000895A patent/AP736A/en active
- 1995-07-06 AT AT95923513T patent/ATE193298T1/de active
- 1995-07-06 CN CN95194960A patent/CN1052010C/zh not_active Expired - Lifetime
- 1995-07-06 US US08/765,758 patent/US6077832A/en not_active Expired - Lifetime
- 1995-07-06 JP JP50355096A patent/JP3225045B2/ja not_active Expired - Lifetime
- 1995-07-06 UA UA97010040A patent/UA66744C2/xx unknown
- 1995-07-06 IL IL11449295A patent/IL114492A/en not_active IP Right Cessation
- 1995-07-06 HR HR950382A patent/HRP950382B1/xx not_active IP Right Cessation
- 1995-07-06 EE EE9700013A patent/EE03568B1/xx unknown
- 1995-07-06 PT PT95923513T patent/PT769017E/pt unknown
- 1995-07-06 KR KR1019970700037A patent/KR100376075B1/ko not_active Expired - Lifetime
- 1995-07-06 YU YU45095A patent/YU49443B/sh unknown
- 1995-07-06 HU HU9700034A patent/HU227679B1/hu unknown
- 1995-07-06 SK SK1688-96A patent/SK282046B6/sk not_active IP Right Cessation
- 1995-07-06 RO RO97-00014A patent/RO117699B1/ro unknown
- 1995-07-06 NZ NZ288722A patent/NZ288722A/en not_active IP Right Cessation
- 1995-07-06 DE DE69517172T patent/DE69517172T2/de not_active Expired - Lifetime
- 1995-07-06 ES ES95923513T patent/ES2147294T3/es not_active Expired - Lifetime
- 1995-07-06 ZA ZA955644A patent/ZA955644B/xx unknown
- 1995-07-06 TJ TJ97000433A patent/TJ270B/xx unknown
- 1995-07-07 TR TR95/00832A patent/TR199500832A2/xx unknown
- 1995-08-04 TW TW084108119A patent/TW418196B/zh not_active IP Right Cessation
- 1995-08-27 SA SA95160202A patent/SA95160202B1/ar unknown
1996
- 1996-12-09 IS IS4394A patent/IS1812B/is unknown
- 1996-12-24 OA OA60942A patent/OA10339A/en unknown
1997
- 1997-01-03 FI FI970032A patent/FI117629B/fi not_active IP Right Cessation
- 1997-01-06 BG BG101118A patent/BG63435B1/bg unknown
- 1997-01-06 NO NO970040A patent/NO308854B1/no not_active IP Right Cessation
1998
- 1998-12-18 US US09/216,719 patent/US5998605A/en not_active Expired - Lifetime
1999
- 1999-04-19 CN CN99105167A patent/CN1236616A/zh active Pending
2000
- 2000-01-21 US US09/489,098 patent/US6307043B1/en not_active Expired - Lifetime
- 2000-06-22 GR GR20000401439T patent/GR3033744T3/el unknown
- 2000-12-14 US US09/738,802 patent/US20010003744A1/en not_active Abandoned
2001
- 2001-11-26 CY CY0100041A patent/CY2249B1/xx unknown

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2130030A1 (de) *	1971-06-18	1972-12-21	Bayer Ag	Fungizide und bakterizide Mittel
WO1992007867A1 (en) *	1990-11-01	1992-05-14	The Regents Of The University Of Michigan	Polysubstituted benzimidazoles as antiviral agents
WO1994008456A1 (en) *	1992-10-21	1994-04-28	The Regents Of The University Of Michigan	Polysubstituted benzimidazoles as antiviral agents

Also Published As

Publication number	Publication date
HRP950382B1 (en)	2000-12-31
EP0769017A1 (en)	1997-04-23
JPH10502356A (ja)	1998-03-03
RO117699B1 (ro)	2002-06-28
YU45095A (sh)	1999-03-04
CZ4097A3 (en)	1997-08-13
HK1003711A1 (en)	1998-11-06
FI117629B (fi)	2006-12-29
MX9606732A (es)	1997-04-30
HUT77285A (hu)	1998-03-30
CN1052010C (zh)	2000-05-03
OA10339A (en)	1997-10-07
DE69517172D1 (de)	2000-06-29
US20010003744A1 (en)	2001-06-14
AP9600895A0 (en)	1997-01-31
CZ290800B6 (cs)	2002-10-16
BG63435B1 (bg)	2002-01-31
EE9700013A (et)	1997-06-16
IS1812B (is)	2002-05-15
ATE193298T1 (de)	2000-06-15
MD1838G2 (ro)	2002-08-31
PT769017E (pt)	2000-09-29
WO1996001833A1 (en)	1996-01-25
US5998605A (en)	1999-12-07
HRP950382A2 (en)	1997-08-31
MD1838F2 (en)	2002-01-31
KR100376075B1 (ko)	2004-02-18
TR199500832A2 (tr)	1996-06-21
AU702248B2 (en)	1999-02-18
CN1236616A (zh)	1999-12-01
SA95160202B1 (ar)	2005-04-16
GEP20002298B (en)	2000-11-25
TJ270B (en)	2000-08-07
PL181136B1 (pl)	2001-06-29
SK168896A3 (en)	1997-09-10
GR3033744T3 (en)	2000-10-31
FI970032A0 (fi)	1997-01-03
IL114492A (en)	2002-05-23
DK0769017T3 (da)	2000-09-11
UA66744C2 (en)	2004-06-15
CN1159194A (zh)	1997-09-10
ZA955644B (en)	1997-01-06
TW418196B (en)	2001-01-11
DE69517172T2 (de)	2000-10-19
YU49443B (sh)	2006-03-03
JP3225045B2 (ja)	2001-11-05
NO970040L (no)	1997-01-29
CY2249B1 (en)	2003-07-04
PL318062A1 (en)	1997-05-12
NO970040D0 (no)	1997-01-06
MY117892A (en)	2004-08-30
EE03568B1 (et)	2001-12-17
HU227679B1 (en)	2011-11-28
NO308854B1 (no)	2000-11-06
FI970032L (fi)	1997-01-03
ES2147294T3 (es)	2000-09-01
HU9700034D0 (en)	1997-02-28
BG101118A (en)	1998-04-30
NZ288722A (en)	1998-07-28
EP0769017B1 (en)	2000-05-24
SK282046B6 (sk)	2001-10-08
GB9413724D0 (en)	1994-08-24
IL114492A0 (en)	1995-11-27
US6077832A (en)	2000-06-20
RU2145963C1 (ru)	2000-02-27
IS4394A (is)	1996-12-09
BR9508237A (pt)	1999-06-01
AU2805195A (en)	1996-02-09
US6307043B1 (en)	2001-10-23

Publication	Publication Date	Title
US6077832A (en)	2000-06-20	Antiviral benzimidazole nucleoside analogues and a method for their preparation
JP4548866B2 (ja)	2010-09-22	ベンゾイミダゾール誘導体
US6617315B1 (en)	2003-09-09	Therapeutic compounds
EP0970100B1 (en)	2003-11-12	Benzimidazole derivatives
CA2193665C (en)	2005-11-01	Benzimidazole derivatives for the treatment and prophylaxis of virus infections
HK1003711B (en)	2000-11-24	Therapeutic compounds
CZ448299A3 (cs)	2000-07-12	Benzimidazolové deriváty, způsob jejich výroby, farmaceutický prostředek obsahující tyto deriváty a použití těchto derivátů
HK1024921B (en)	2003-11-07	Benzimidazole derivatives