BR112014019402B1 - Composto 2-aril-benzofuran-7-carboxamida, ou sal farmacologicamente aceitável do mesmo e método para a preparação do composto - Google Patents
Composto 2-aril-benzofuran-7-carboxamida, ou sal farmacologicamente aceitável do mesmo e método para a preparação do composto Download PDFInfo
- Publication number
- BR112014019402B1 BR112014019402B1 BR112014019402-5A BR112014019402A BR112014019402B1 BR 112014019402 B1 BR112014019402 B1 BR 112014019402B1 BR 112014019402 A BR112014019402 A BR 112014019402A BR 112014019402 B1 BR112014019402 B1 BR 112014019402B1
- Authority
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- Brazil
- Prior art keywords
- compound
- methyl
- mmol
- preparation
- benzofuran
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 83
- 238000000034 method Methods 0.000 title claims abstract description 24
- 150000003839 salts Chemical class 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 129
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 48
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 10
- 229910052731 fluorine Chemical group 0.000 claims abstract description 8
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 7
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 7
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 5
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract description 5
- 229910052801 chlorine Chemical group 0.000 claims abstract description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 3
- -1 piperidine-4-yl Chemical group 0.000 claims description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 238000003786 synthesis reaction Methods 0.000 claims description 6
- 229940125782 compound 2 Drugs 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims description 4
- 229940126214 compound 3 Drugs 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 claims description 3
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 2
- 238000005915 ammonolysis reaction Methods 0.000 claims description 2
- 229940125898 compound 5 Drugs 0.000 claims description 2
- 238000005886 esterification reaction Methods 0.000 claims description 2
- 238000005658 halogenation reaction Methods 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 238000006192 iodination reaction Methods 0.000 claims description 2
- 238000007363 ring formation reaction Methods 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 abstract description 6
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 5
- 125000001424 substituent group Chemical group 0.000 abstract description 4
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 90
- 238000005160 1H NMR spectroscopy Methods 0.000 description 57
- 239000003153 chemical reaction reagent Substances 0.000 description 53
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 22
- 239000007788 liquid Substances 0.000 description 21
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 18
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
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- SPCXJKWATXURQS-UHFFFAOYSA-N methyl 5-fluoro-2-hydroxy-3-iodobenzoate Chemical compound COC(=O)c1cc(F)cc(I)c1O SPCXJKWATXURQS-UHFFFAOYSA-N 0.000 description 10
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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
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- Chemical & Material Sciences (AREA)
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- 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)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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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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| BR112014019402A2 BR112014019402A2 (https=) | 2017-06-20 |
| BR112014019402A8 BR112014019402A8 (pt) | 2017-07-11 |
| BR112014019402B1 true BR112014019402B1 (pt) | 2020-12-15 |
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| RU (1) | RU2583900C2 (https=) |
| WO (1) | WO2013117120A1 (https=) |
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| 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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| 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 |
| US7435837B2 (en) * | 2003-10-24 | 2008-10-14 | Wyeth | Dihydrobenzofuranyl alkanamine derivatives and methods for using same |
| 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 |
| WO2007059230A2 (en) * | 2005-11-15 | 2007-05-24 | Abbott Laboratories | Substituted 1h-benzimidazole-4-carboxamides are potent parp inhibitors |
| CA2647373C (en) * | 2006-05-02 | 2014-03-18 | Abbott Laboratories | Substituted 1h-benzimidazole-4-carboxamides are potent parp inhibitors |
| 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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| JP5926821B2 (ja) | 2016-05-25 |
| EP2813495B1 (en) | 2016-09-28 |
| CN103242273A (zh) | 2013-08-14 |
| 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 |
| RU2583900C2 (ru) | 2016-05-10 |
| 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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