SK282046B6 - Benzimidazolové deriváty, spôsob ich prípravy, farmaceutické prostriedky s ich obsahom a ich použitie - Google Patents
Benzimidazolové deriváty, spôsob ich prípravy, farmaceutické prostriedky s ich obsahom a ich použitie Download PDFInfo
- Publication number
- SK282046B6 SK282046B6 SK1688-96A SK168896A SK282046B6 SK 282046 B6 SK282046 B6 SK 282046B6 SK 168896 A SK168896 A SK 168896A SK 282046 B6 SK282046 B6 SK 282046B6
- Authority
- SK
- Slovakia
- Prior art keywords
- benzimidazole
- formula
- dichloro
- carbon atoms
- mmol
- Prior art date
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- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
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- BHRZNVHARXXAHW-UHFFFAOYSA-N sec-butylamine Chemical compound CCC(C)N BHRZNVHARXXAHW-UHFFFAOYSA-N 0.000 description 1
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
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- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 1
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- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
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- 208000008732 thymoma Diseases 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
- 229940093257 valacyclovir Drugs 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
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- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 1
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)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
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 |
|---|---|
| SK168896A3 SK168896A3 (en) | 1997-09-10 |
| SK282046B6 true SK282046B6 (sk) | 2001-10-08 |
Family
ID=10757983
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1688-96A SK282046B6 (sk) | 1994-07-07 | 1995-07-06 | Benzimidazolové deriváty, spôsob ich prípravy, farmaceutické prostriedky s ich obsahom a ich použitie |
Country Status (43)
| Country | Link |
|---|---|
| US (4) | US6077832A (cs) |
| EP (1) | EP0769017B1 (cs) |
| JP (1) | JP3225045B2 (cs) |
| KR (1) | KR100376075B1 (cs) |
| CN (2) | CN1052010C (cs) |
| AP (1) | AP736A (cs) |
| AT (1) | ATE193298T1 (cs) |
| AU (1) | AU702248B2 (cs) |
| BG (1) | BG63435B1 (cs) |
| BR (1) | BR9508237A (cs) |
| CY (1) | CY2249B1 (cs) |
| CZ (1) | CZ290800B6 (cs) |
| DE (1) | DE69517172T2 (cs) |
| DK (1) | DK0769017T3 (cs) |
| EE (1) | EE03568B1 (cs) |
| ES (1) | ES2147294T3 (cs) |
| FI (1) | FI117629B (cs) |
| GB (1) | GB9413724D0 (cs) |
| GE (1) | GEP20002298B (cs) |
| GR (1) | GR3033744T3 (cs) |
| HR (1) | HRP950382B1 (cs) |
| HU (1) | HU227679B1 (cs) |
| IL (1) | IL114492A (cs) |
| IS (1) | IS1812B (cs) |
| MD (1) | MD1838G2 (cs) |
| MX (1) | MX9606732A (cs) |
| MY (1) | MY117892A (cs) |
| NO (1) | NO308854B1 (cs) |
| NZ (1) | NZ288722A (cs) |
| OA (1) | OA10339A (cs) |
| PL (1) | PL181136B1 (cs) |
| PT (1) | PT769017E (cs) |
| RO (1) | RO117699B1 (cs) |
| RU (1) | RU2145963C1 (cs) |
| SA (1) | SA95160202B1 (cs) |
| SK (1) | SK282046B6 (cs) |
| TJ (1) | TJ270B (cs) |
| TR (1) | TR199500832A2 (cs) |
| TW (1) | TW418196B (cs) |
| UA (1) | UA66744C2 (cs) |
| WO (1) | WO1996001833A1 (cs) |
| YU (1) | YU49443B (cs) |
| ZA (1) | ZA955644B (cs) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9413724D0 (en) * | 1994-07-07 | 1994-08-24 | Wellcome Found | Therapeutic nucleosides |
| CA2223814A1 (en) * | 1995-08-18 | 1997-02-27 | John C. Drach | 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 |
| WO1997027205A1 (en) | 1996-01-23 | 1997-07-31 | The Regents Of The University Of Michigan | Imidazo[1,2-a]pyridine c-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 |
| EP0970100B1 (en) | 1997-02-13 | 2003-11-12 | Glaxo Group Limited | Benzimidazole derivatives |
| KR20010020465A (ko) | 1997-06-10 | 2001-03-15 | 그레이엄 브레레톤, 레슬리 에드워즈 | 벤즈이미다졸 유도체 |
| US6455506B1 (en) | 1997-07-30 | 2002-09-24 | Smithkline Beecham Corporation | 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 |
| RU2437892C2 (ru) * | 2002-06-28 | 2011-12-27 | Айденикс (Кайман) Лимитед | Модифицированные 2- и 3-нуклеозиды и их применение для получения лекарственного средства, обладающего ингибирующей активностью в отношении вируса гепатита с |
| JP2007526017A (ja) | 2003-06-25 | 2007-09-13 | エイセル インコーポレイテッド | 組織修復用に調整されたマトリクス組成物 |
| 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 |
| WO2006115137A1 (ja) * | 2005-04-22 | 2006-11-02 | Kissei Pharmaceutical Co., Ltd. | 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 |
| WO2012138907A2 (en) * | 2011-04-05 | 2012-10-11 | Translational Genomics Research Institute | Solid forms of curcumin |
| WO2014004939A1 (en) | 2012-06-29 | 2014-01-03 | The Procter & Gamble Company | Textured fibrous webs, apparatus and methods for forming textured fibrous webs |
| ES2885424T3 (es) | 2013-03-15 | 2021-12-13 | Knopp Biosciences Llc | Imidazo(4,5-B)piridin-2-il amidas como activadores del canal Kv7 |
| PT3572405T (pt) | 2014-09-12 | 2023-10-26 | Biohaven Therapeutics Ltd | Benzoimidazol-1,2-ilamidas como ativadores de 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 |
| CN112771039A (zh) | 2018-03-19 | 2021-05-07 | 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 |
| JP7376108B2 (ja) * | 2020-06-23 | 2023-11-08 | バイオメトリックス テクノロジーズ インコーポレイテッド | 新規なベンズイミダゾール誘導体、その製造方法及びその抗癌剤または抗ウイルス剤としての用途 |
| WO2024081308A1 (en) | 2022-10-12 | 2024-04-18 | Takeda Pharmaceutical Company Limited | Method of preparing maribavir |
| 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 |
Family Cites Families (23)
| 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 (cs) * | 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 |
| DE2130030A1 (de) * | 1971-06-18 | 1972-12-21 | Bayer Ag | Fungizide und bakterizide Mittel |
| 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 |
| US5248672A (en) * | 1990-11-01 | 1993-09-28 | The Regents Of The University Of Michigan | Polysubstituted benzimidazole nucleosides as antiviral agents |
| 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 |
| WO1994008456A1 (en) * | 1992-10-21 | 1994-04-28 | The Regents Of The University Of Michigan | Polysubstituted benzimidazoles as antiviral agents |
| 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 |
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1994
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