RU2583900C2 - Соединения 2-арилбензофуран-7-формамида, способ их получения и применение - Google Patents
Соединения 2-арилбензофуран-7-формамида, способ их получения и применение Download PDFInfo
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- RU2583900C2 RU2583900C2 RU2014132159/04A RU2014132159A RU2583900C2 RU 2583900 C2 RU2583900 C2 RU 2583900C2 RU 2014132159/04 A RU2014132159/04 A RU 2014132159/04A RU 2014132159 A RU2014132159 A RU 2014132159A RU 2583900 C2 RU2583900 C2 RU 2583900C2
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- compound
- methyl
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- 238000000034 method Methods 0.000 title claims abstract description 34
- 150000001875 compounds Chemical class 0.000 claims abstract description 80
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 40
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- 229940079593 drug Drugs 0.000 claims abstract description 11
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 11
- 229910052731 fluorine Chemical group 0.000 claims abstract description 8
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- XPFJYKARVSSRHE-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O XPFJYKARVSSRHE-UHFFFAOYSA-K 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/81—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/307—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Furan Compounds (AREA)
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| CN201210028895.0A CN103242273B (zh) | 2012-02-09 | 2012-02-09 | 2-芳基苯并呋喃-7-甲酰胺类化合物、其制备方法及用途 |
| CN201210028895.0 | 2012-02-09 | ||
| PCT/CN2013/070410 WO2013117120A1 (zh) | 2012-02-09 | 2013-01-14 | 2-芳基苯并呋喃-7-甲酰胺类化合物、其制备方法及用途 |
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| RU2014132159A RU2014132159A (ru) | 2016-03-27 |
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| EP (1) | EP2813495B1 (https=) |
| JP (1) | JP5926821B2 (https=) |
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| BR (1) | BR112014019402B1 (https=) |
| CA (1) | CA2863988C (https=) |
| RU (1) | RU2583900C2 (https=) |
| WO (1) | WO2013117120A1 (https=) |
Cited By (1)
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| RU2783418C1 (ru) * | 2018-05-31 | 2022-11-14 | Шангхаи Институте Оф Материа Медика, Чайнесе Академи Оф Сайнсес | Способ получения полиморфа гидрохлорида 2-[4-(метиламинометил)фенил]-5-фтор-бензофуран-7-карбоксамида |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102627620B (zh) * | 2012-04-10 | 2015-12-16 | 江苏先声药物研究有限公司 | 一类苯并呋喃衍生物及其医药应用 |
| PL2938598T3 (pl) | 2012-12-31 | 2017-05-31 | Cadila Healthcare Limited | Podstawione pochodne ftalazyn-1 (2H)-onu jako selektywne inhibitory polimerazy-1 poli(ADP-rybozy) |
| CN105272936B (zh) * | 2014-05-27 | 2019-05-17 | 中国科学院上海药物研究所 | 一类氮芳基苯并噻唑类parp抑制剂及其制备方法和用途 |
| CN109134409B (zh) * | 2017-06-14 | 2023-09-29 | 中国科学院上海药物研究所 | 盐酸美呋哌瑞多晶型物及其制备方法与应用 |
| CN111320596B (zh) * | 2018-12-14 | 2024-07-05 | 甫康（上海）健康科技有限责任公司 | 盐酸美呋哌瑞多晶型物及其制备方法 |
| US20230094843A1 (en) * | 2019-12-31 | 2023-03-30 | Fukang (Shanghai) Health Technology Co., Ltd | Pharmaceutical combination for treating tumors and application thereof |
| JP2023514794A (ja) * | 2020-02-24 | 2023-04-10 | フーカン（シャンハイ） ヘルス テクノロジー カンパニー、 リミテッド | ポリａｄｐリボースポリメラーゼ阻害剤の抗コロナウイルス応用 |
| WO2024187321A1 (zh) * | 2023-03-10 | 2024-09-19 | 甫康（上海）健康科技有限责任公司 | 含有egfr抑制剂的药物组合物及其制备方法和应用 |
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| WO2007059230A2 (en) * | 2005-11-15 | 2007-05-24 | Abbott Laboratories | Substituted 1h-benzimidazole-4-carboxamides are potent parp inhibitors |
| WO2007131016A2 (en) * | 2006-05-02 | 2007-11-15 | Abbott Laboratories | Substituted 1h-benzimidazole-4-carboxamides are potent parp inhibitors |
| RU2006117789A (ru) * | 2003-10-24 | 2007-11-27 | Уайт (Us) | Производные дигидробензофуранилалканамина в качестве агонистов 5нт2с |
Family Cites Families (16)
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|---|---|---|---|---|
| IL87451A0 (en) | 1987-09-04 | 1989-01-31 | Tanabe Seiyaku Co | Benzofuran derivatives,their preparation and pharmaceutical compositions containing them |
| JP2002515488A (ja) * | 1998-05-15 | 2002-05-28 | ギルフォード ファーマシューティカルズ インコーポレイテッド | カルボキサミド化合物、組成物、及びｐａｒｐ活性の抑制方法 |
| DE59911249D1 (de) * | 1998-11-03 | 2005-01-13 | Abbott Gmbh & Co Kg | Substituierte 2-phenylbenzimidazole, deren herstellung und anwendung |
| DK1131301T3 (da) * | 1998-11-17 | 2006-01-09 | Abbott Gmbh & Co Kg | 2-phenylbenzimidazoler og 2-phenylindoler, fremstilling af anvendelse heraf |
| DE10022925A1 (de) * | 2000-05-11 | 2001-11-15 | Basf Ag | Substituierte Indole als PARP-Inhibitoren |
| DE10351315A1 (de) | 2003-10-31 | 2005-06-16 | Aventis Pharma Deutschland Gmbh | 2-Phenyl-benzofuran-Derivate, Verfahren zur ihrer Herstellung und ihre Verwendung |
| DK1794163T3 (da) * | 2004-09-22 | 2010-04-12 | Pfizer | Fremgangsmåde til fremstilling af poly(ADP-ribose)polymeraseinhibitorer |
| DK2120579T3 (da) * | 2006-12-28 | 2014-02-03 | Abbvie Inc | Inhibitorer af poly(ADP-ripose)polymerase |
| WO2008098978A2 (en) | 2007-02-16 | 2008-08-21 | Glaxo Group Limited | Benzofuran compounds useful in the treatment of conditions mediated by the action of pge2 at the ep1 receptor |
| WO2009009417A2 (en) | 2007-07-06 | 2009-01-15 | Wyeth | Pharmaceutical compositions and methods of preventing, treating, or inhibiting inflammatory diseases, disorders, or conditions of the skin, and diseases, disorders, or conditions associated with collagen depletion |
| WO2009099736A2 (en) * | 2008-02-06 | 2009-08-13 | Lead Therapeutics, Inc. | Benzoxazole carboxamide inhibitors of poly(adp-ribose)polymerase (parp) |
| GB0806656D0 (en) | 2008-04-11 | 2008-05-14 | Karobio Ab | Novel estrogen receptor ligands |
| US8569336B2 (en) * | 2008-11-10 | 2013-10-29 | Ling Tong | Compounds for the treatment of inflammatory disorders |
| WO2011022679A2 (en) | 2009-08-20 | 2011-02-24 | University Of Tennessee Research Foundation, The | Benzofuran cannabinoid compounds and related methods of use |
| GB0919380D0 (en) * | 2009-11-04 | 2009-12-23 | Almac Discovery Ltd | Pharmaceutical compouds |
| CN102627620B (zh) * | 2012-04-10 | 2015-12-16 | 江苏先声药物研究有限公司 | 一类苯并呋喃衍生物及其医药应用 |
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2012
- 2012-02-09 CN CN201210028895.0A patent/CN103242273B/zh active Active
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2013
- 2013-01-14 US US14/375,742 patent/US9533965B2/en active Active
- 2013-01-14 JP JP2014555927A patent/JP5926821B2/ja active Active
- 2013-01-14 CA CA2863988A patent/CA2863988C/en active Active
- 2013-01-14 WO PCT/CN2013/070410 patent/WO2013117120A1/zh not_active Ceased
- 2013-01-14 RU RU2014132159/04A patent/RU2583900C2/ru active
- 2013-01-14 BR BR112014019402-5A patent/BR112014019402B1/pt active IP Right Grant
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2006117789A (ru) * | 2003-10-24 | 2007-11-27 | Уайт (Us) | Производные дигидробензофуранилалканамина в качестве агонистов 5нт2с |
| WO2007059230A2 (en) * | 2005-11-15 | 2007-05-24 | Abbott Laboratories | Substituted 1h-benzimidazole-4-carboxamides are potent parp inhibitors |
| WO2007131016A2 (en) * | 2006-05-02 | 2007-11-15 | Abbott Laboratories | Substituted 1h-benzimidazole-4-carboxamides are potent parp inhibitors |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2783418C9 (ru) * | 2017-06-14 | 2023-02-20 | Шангхаи Институте Оф Материа Медика, Чайнесе Академи Оф Сайнсес | Способ получения полиморфа гидрохлорида 2-[4-(метиламинометил)фенил]-5-фтор-бензофуран-7-карбоксамида |
| RU2783418C1 (ru) * | 2018-05-31 | 2022-11-14 | Шангхаи Институте Оф Материа Медика, Чайнесе Академи Оф Сайнсес | Способ получения полиморфа гидрохлорида 2-[4-(метиламинометил)фенил]-5-фтор-бензофуран-7-карбоксамида |
Also Published As
| Publication number | Publication date |
|---|---|
| JP5926821B2 (ja) | 2016-05-25 |
| EP2813495B1 (en) | 2016-09-28 |
| CN103242273A (zh) | 2013-08-14 |
| BR112014019402B1 (pt) | 2020-12-15 |
| BR112014019402A8 (pt) | 2017-07-11 |
| JP2015511942A (ja) | 2015-04-23 |
| CA2863988C (en) | 2016-03-22 |
| US20150018542A1 (en) | 2015-01-15 |
| BR112014019402A2 (https=) | 2017-06-20 |
| US9533965B2 (en) | 2017-01-03 |
| CN103242273B (zh) | 2015-06-03 |
| EP2813495A4 (en) | 2015-06-17 |
| RU2014132159A (ru) | 2016-03-27 |
| EP2813495A1 (en) | 2014-12-17 |
| WO2013117120A1 (zh) | 2013-08-15 |
| CA2863988A1 (en) | 2013-08-15 |
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