CN103987697B - 作为因子xia抑制剂的取代的四氢异喹啉化合物 - Google Patents
作为因子xia抑制剂的取代的四氢异喹啉化合物 Download PDFInfo
- Publication number
- CN103987697B CN103987697B CN201280061670.3A CN201280061670A CN103987697B CN 103987697 B CN103987697 B CN 103987697B CN 201280061670 A CN201280061670 A CN 201280061670A CN 103987697 B CN103987697 B CN 103987697B
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- Prior art keywords
- phenyl
- bases
- alkyl
- chloro
- tetrazolium
- Prior art date
- 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.)
- Expired - Fee Related
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- 0 CC1=CC2=CN(*)N=CC2C=C1 Chemical compound CC1=CC2=CN(*)N=CC2C=C1 0.000 description 6
- AYPLNGXIRFCAJC-DBXZZFOPSA-N CC(C)(Cc(c(/C=C/C(N(CC1)C(C(Nc(cc2)ccc2C(O)=O)=O)c2c1[n](Cc1ccccc1)nc2C)=O)c1F)ccc1Cl)/C=N\N=N Chemical compound CC(C)(Cc(c(/C=C/C(N(CC1)C(C(Nc(cc2)ccc2C(O)=O)=O)c2c1[n](Cc1ccccc1)nc2C)=O)c1F)ccc1Cl)/C=N\N=N AYPLNGXIRFCAJC-DBXZZFOPSA-N 0.000 description 1
- DHOZGVQOZATZGP-UHFFFAOYSA-N CC(CCN)C=C Chemical compound CC(CCN)C=C DHOZGVQOZATZGP-UHFFFAOYSA-N 0.000 description 1
- VUZKKQLAKICMKV-UHFFFAOYSA-N C[N]1(C2)(C2C1)#C Chemical compound C[N]1(C2)(C2C1)#C VUZKKQLAKICMKV-UHFFFAOYSA-N 0.000 description 1
- KQLSFTLKDUMXDM-RUDMXATFSA-N C[n]1nc(CCN(C2C(Nc(cc3)ccc3C(O)=O)=O)C(/C=C/c3cc(Cl)ccc3-[n]3nnnc3)=O)c2c1 Chemical compound C[n]1nc(CCN(C2C(Nc(cc3)ccc3C(O)=O)=O)C(/C=C/c3cc(Cl)ccc3-[n]3nnnc3)=O)c2c1 KQLSFTLKDUMXDM-RUDMXATFSA-N 0.000 description 1
- BIRRBRQQDQJKMQ-UHFFFAOYSA-N N#Cc1cc([n](C(OCc2ccccc2)=O)nc2)c2cc1 Chemical compound N#Cc1cc([n](C(OCc2ccccc2)=O)nc2)c2cc1 BIRRBRQQDQJKMQ-UHFFFAOYSA-N 0.000 description 1
- XCTSAVLSNJIQFA-MDWZMJQESA-N OC(c(cc1)ccc1NC(C(c1c[n](Cc2ccccc2)nc1CC1)[N-]1C(/C=C/c1cc(Cl)ccc1-[n]1nnnc1)=O)=O)=O Chemical compound OC(c(cc1)ccc1NC(C(c1c[n](Cc2ccccc2)nc1CC1)[N-]1C(/C=C/c1cc(Cl)ccc1-[n]1nnnc1)=O)=O)=O XCTSAVLSNJIQFA-MDWZMJQESA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 to carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161547305P | 2011-10-14 | 2011-10-14 | |
| US61/547305 | 2011-10-14 | ||
| PCT/US2012/059859 WO2013055984A1 (en) | 2011-10-14 | 2012-10-12 | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103987697A CN103987697A (zh) | 2014-08-13 |
| CN103987697B true CN103987697B (zh) | 2017-04-26 |
Family
ID=47080862
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201280061670.3A Expired - Fee Related CN103987697B (zh) | 2011-10-14 | 2012-10-12 | 作为因子xia抑制剂的取代的四氢异喹啉化合物 |
Country Status (7)
| Country | Link |
|---|---|
| US (5) | US9108951B2 (enExample) |
| EP (2) | EP2766345B1 (enExample) |
| JP (1) | JP6033317B2 (enExample) |
| CN (1) | CN103987697B (enExample) |
| ES (2) | ES2572908T3 (enExample) |
| IN (1) | IN2014CN02806A (enExample) |
| WO (1) | WO2013055984A1 (enExample) |
Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101843542B1 (ko) | 2010-02-11 | 2018-03-30 | 브리스톨-마이어스 스큅 컴퍼니 | 인자 ＸＩａ 억제제로서의 마크로사이클 |
| TW201319068A (zh) | 2011-08-05 | 2013-05-16 | 必治妥美雅史谷比公司 | 作為ｘｉａ因子抑制劑之環狀ｐ１接合劑 |
| TW201311689A (zh) | 2011-08-05 | 2013-03-16 | 必治妥美雅史谷比公司 | 作為因子ｘｉａ抑制劑之新穎巨環化合物 |
| JP6033317B2 (ja) | 2011-10-14 | 2016-11-30 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 第ｘｉａ因子阻害剤としての置換テトラヒドロイソキノリン化合物 |
| EP2766347B1 (en) | 2011-10-14 | 2016-05-04 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| UY34393A (es) | 2011-10-14 | 2013-04-30 | Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware | Compuestos de tetrahidroisoquinolina sustituidos como inhibidores del factor xia |
| BR112015002081A2 (pt) | 2012-08-03 | 2017-07-04 | Bristol Myers Squibb Co | di-hidropiridona p1 como inibidores de fator xia |
| EA025392B1 (ru) | 2012-08-03 | 2016-12-30 | Бристол-Маерс Сквибб Компани | Дигидропиридон р1 в качестве ингибиторов фактора xia |
| US9403774B2 (en) | 2012-10-12 | 2016-08-02 | Bristol-Myers Squibb Company | Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| EA032092B1 (ru) | 2012-10-12 | 2019-04-30 | Бристол-Майерс Сквибб Компани | Кристаллические формы ингибитора фактора xia |
| WO2014059202A1 (en) | 2012-10-12 | 2014-04-17 | Bristol-Myers Squibb Company | Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| US9834520B2 (en) | 2013-03-14 | 2017-12-05 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
| EP2978751B1 (en) | 2013-03-25 | 2018-12-05 | Bristol-Myers Squibb Company | Tetrahydroisoquinolines containing substituted azoles as factor xia inhibitors |
| ES2950424T3 (es) | 2013-07-03 | 2023-10-09 | Takeda Pharmaceuticals Co | Compuesto de amida |
| JP6427491B2 (ja) | 2013-07-03 | 2018-11-21 | 武田薬品工業株式会社 | 複素環化合物 |
| EP3049435A4 (en) * | 2013-09-27 | 2017-03-29 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
| US20160257668A1 (en) * | 2013-10-07 | 2016-09-08 | Merck Sharp & Dohme Corp. | Factor XIa Inhibitors |
| NO2760821T3 (enExample) | 2014-01-31 | 2018-03-10 | ||
| UY35971A (es) | 2014-01-31 | 2015-07-31 | Bristol Myers Squibb Company Una Corporación Del Estado De Delaware | Macrociclos con grupos p2? aromáticos como inhibidores del factor xia |
| EP3104702B1 (en) | 2014-02-11 | 2022-08-10 | Merck Sharp & Dohme LLC | Factor xia inhibitors |
| EP3104703B1 (en) | 2014-02-11 | 2020-11-18 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
| EP3134408B1 (en) * | 2014-04-22 | 2020-08-12 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
| US9693998B2 (en) * | 2014-05-16 | 2017-07-04 | Cumberland Pharmaceuticals, Inc. | Compositions and methods of treating cardiac fibrosis with ifetroban |
| US10093629B2 (en) | 2014-07-01 | 2018-10-09 | Takeda Pharmaceutical Company Limited | Heterocyclic compounds and their use as retinoid-related orphan receptor (ROR) gamma-T inhibitors |
| EP3180317B1 (en) | 2014-07-28 | 2021-04-14 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
| KR102633122B1 (ko) | 2014-08-01 | 2024-02-05 | 누에볼루션 에이/에스 | 브로모도메인에 대하여 활성을 갖는 화합물 |
| CN105461688B (zh) * | 2014-08-26 | 2017-12-29 | 上海医药工业研究院 | 苯并咪唑化合物k的合成方法 |
| CN107074821B (zh) | 2014-09-04 | 2020-05-22 | 百时美施贵宝公司 | 为fxia抑制剂的二酰胺大环化合物 |
| US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
| JP6799530B2 (ja) * | 2014-10-01 | 2020-12-16 | メディミューン リミテッド | チカグレロルに対する抗体および使用方法 |
| CN108026083B (zh) | 2015-06-19 | 2021-08-27 | 百时美施贵宝公司 | 作为因子xia抑制剂的二酰胺大环 |
| KR20220137141A (ko) | 2015-06-30 | 2022-10-11 | 큠버랜드 파마슈티컬즈 인코포레이티드 | Ａｅｒｄ/천식에서 트롬복산 수용체 길항제 |
| RS62639B1 (sr) | 2015-07-06 | 2021-12-31 | Alkermes Inc | Hetero-halo inhibitori histonskih deacetilaza |
| EP3319968A1 (en) | 2015-07-06 | 2018-05-16 | Rodin Therapeutics, Inc. | Heterobicyclic n-aminophenyl-amides as inhibitors of histone deacetylase |
| EP3868753B1 (en) | 2015-07-29 | 2022-12-21 | Bristol-Myers Squibb Company | Factor xia macrocyclic inhibitors bearing a non-aromatic p2' group |
| JP6629958B2 (ja) | 2015-07-29 | 2020-01-15 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | アルキルまたはシクロアルキルＰ２’基を担持する大員環の第ＸＩａ因子阻害剤 |
| EP3371162B1 (en) | 2015-10-29 | 2022-01-26 | Merck Sharp & Dohme Corp. | Macrocyclic spirocarbamate derivatives as factor xia inhibitors, pharmaceutically acceptable compositions and their use |
| MA43128A (fr) | 2015-10-29 | 2018-09-05 | Merck Sharp & Dohme | Inhibiteurs du facteur xia |
| KR102708936B1 (ko) | 2015-11-20 | 2024-09-25 | 포르마 세라퓨틱스 인크. | 유비퀴틴-특이적 프로테아제 1 억제제로서의 퓨리논 |
| JP6844890B2 (ja) * | 2016-01-07 | 2021-03-17 | 藤森工業株式会社 | 採血管、試薬及びそれらを利用した血液性状分析方法 |
| CN107540659A (zh) * | 2016-06-29 | 2018-01-05 | 四川科伦博泰生物医药股份有限公司 | 四氢异喹啉类化合物、其制备方法、药物组合物及其用途 |
| US10143681B2 (en) | 2016-08-22 | 2018-12-04 | Merck Sharp & Dohme Corp. | Factor XIa inhibitors |
| JP6756925B2 (ja) | 2017-01-11 | 2020-09-16 | ロダン・セラピューティクス，インコーポレーテッド | ヒストンデアセチラーゼの二環式阻害剤 |
| ES2914355T3 (es) | 2017-08-07 | 2022-06-09 | Alkermes Inc | Inhibidores bicíclicos de la histona desacetilasa |
| CN109721539B (zh) * | 2017-10-27 | 2021-07-09 | 天津药物研究院有限公司 | 吡唑酰胺类衍生物及其制备方法和用途 |
| CN109867660A (zh) * | 2017-12-01 | 2019-06-11 | 四川科伦博泰生物医药股份有限公司 | 含季铵离子的四氢异喹啉酰胺化合物及其药物用途 |
| US11541049B2 (en) | 2018-03-28 | 2023-01-03 | Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. | Tetrahydroisoquinoline derivatives, preparation process and use thereof |
| WO2020065613A1 (en) * | 2018-09-28 | 2020-04-02 | Janssen Pharmaceutica Nv | Monoacylglycerol lipase modulators |
| MA53722A (fr) * | 2018-09-28 | 2022-03-30 | Janssen Pharmaceutica Nv | Modulateurs de la monoacylglycérol lipase |
| LT3870578T (lt) * | 2018-10-22 | 2023-12-11 | C4X Discovery Limited | Terapiniai junginiai |
| WO2020094156A1 (zh) * | 2018-11-11 | 2020-05-14 | 上海海雁医药科技有限公司 | 双杂环取代的吡啶-2(1h)-酮衍生物、其制法与医药上的用途 |
| EP4038070B1 (en) | 2019-09-30 | 2025-07-09 | Janssen Pharmaceutica NV | Radiolabelled mgl pet ligands |
| WO2021121371A1 (zh) * | 2019-12-19 | 2021-06-24 | 贝达药业股份有限公司 | Kras g12c抑制剂及其在医药上的应用 |
| US20230312560A1 (en) * | 2020-07-22 | 2023-10-05 | Janssen Pharmaceutica Nv | Compounds useful as factor xia inhibitors |
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Also Published As
| Publication number | Publication date |
|---|---|
| US9725435B2 (en) | 2017-08-08 |
| CN103987697A (zh) | 2014-08-13 |
| US20140275061A1 (en) | 2014-09-18 |
| ES2572908T3 (es) | 2016-06-03 |
| ES2699226T3 (es) | 2019-02-08 |
| EP2899183B1 (en) | 2018-09-19 |
| US20170305880A1 (en) | 2017-10-26 |
| US20160289209A1 (en) | 2016-10-06 |
| US20180265494A1 (en) | 2018-09-20 |
| JP2014528479A (ja) | 2014-10-27 |
| WO2013055984A1 (en) | 2013-04-18 |
| EP2766345B1 (en) | 2016-03-16 |
| EP2899183A1 (en) | 2015-07-29 |
| EP2766345A1 (en) | 2014-08-20 |
| JP6033317B2 (ja) | 2016-11-30 |
| US20150315200A1 (en) | 2015-11-05 |
| IN2014CN02806A (enExample) | 2015-07-03 |
| US9108951B2 (en) | 2015-08-18 |
| US10000466B2 (en) | 2018-06-19 |
| US9394276B2 (en) | 2016-07-19 |
| US10906886B2 (en) | 2021-02-02 |
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