JP6479763B2 - 第xia因子阻害剤としての置換アゾール含有のテトラヒドロイソキノリン - Google Patents
第xia因子阻害剤としての置換アゾール含有のテトラヒドロイソキノリン Download PDFInfo
- Publication number
- JP6479763B2 JP6479763B2 JP2016505527A JP2016505527A JP6479763B2 JP 6479763 B2 JP6479763 B2 JP 6479763B2 JP 2016505527 A JP2016505527 A JP 2016505527A JP 2016505527 A JP2016505527 A JP 2016505527A JP 6479763 B2 JP6479763 B2 JP 6479763B2
- Authority
- JP
- Japan
- Prior art keywords
- carbonyl
- tetrahydroisoquinoline
- chloro
- fluorophenyl
- benzoic acid
- 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
Links
- 0 CN(CC1)C(C(N*(I)=C)=O)c2c1c(*I)ccc2 Chemical compound CN(CC1)C(C(N*(I)=C)=O)c2c1c(*I)ccc2 0.000 description 11
- VOFBKPLGCKRATB-UHFFFAOYSA-N CC(C1)(C(O)=O)ON=C1c(cccc1Cl)c1F Chemical compound CC(C1)(C(O)=O)ON=C1c(cccc1Cl)c1F VOFBKPLGCKRATB-UHFFFAOYSA-N 0.000 description 1
- LEGCVLXVQJXNEL-UHFFFAOYSA-N CC1(COc2cccc(C3C(Nc(cc4)ccc4C(O)=O)=O)c2CCN3C(c2c[n](-c(cccc3Cl)c3F)nn2)=O)COC1 Chemical compound CC1(COc2cccc(C3C(Nc(cc4)ccc4C(O)=O)=O)c2CCN3C(c2c[n](-c(cccc3Cl)c3F)nn2)=O)COC1 LEGCVLXVQJXNEL-UHFFFAOYSA-N 0.000 description 1
- DJUCOOVKTPLJLE-UHFFFAOYSA-N CN(C)C(CC1)CCN1c1cccc(C2C(Nc(cc3)ccc3-c3ncc[o]3)=O)c1CCN2C(c1c[n](-c2cccc(Cl)c2F)nc1)=O Chemical compound CN(C)C(CC1)CCN1c1cccc(C2C(Nc(cc3)ccc3-c3ncc[o]3)=O)c1CCN2C(c1c[n](-c2cccc(Cl)c2F)nc1)=O DJUCOOVKTPLJLE-UHFFFAOYSA-N 0.000 description 1
- RZCBNXHMENKKFK-PQHLKRTFSA-N CNC(c(nc1)ccc1-c1c(CCN([C@H]2C(Nc(cc3)ccc3C(O)=O)=O)C([C@@H](C3)ON=C3c(cccc3Cl)c3F)=O)c2ccc1)=O Chemical compound CNC(c(nc1)ccc1-c1c(CCN([C@H]2C(Nc(cc3)ccc3C(O)=O)=O)C([C@@H](C3)ON=C3c(cccc3Cl)c3F)=O)c2ccc1)=O RZCBNXHMENKKFK-PQHLKRTFSA-N 0.000 description 1
- PTJPEVRPDJCNBG-MRIBFJTASA-N Cc(c(N/C=C(/C(O)[O]=C)\C=N)ccc1)c1Cl Chemical compound Cc(c(N/C=C(/C(O)[O]=C)\C=N)ccc1)c1Cl PTJPEVRPDJCNBG-MRIBFJTASA-N 0.000 description 1
- LNKXXEMOPNVZGM-UHFFFAOYSA-N Cc1n[n](C)c(CC2)c1C(C(Nc(cc1)ccc1C(O)=O)=O)N2C(c1c[n](-c(cccc2Cl)c2F)nn1)=O Chemical compound Cc1n[n](C)c(CC2)c1C(C(Nc(cc1)ccc1C(O)=O)=O)N2C(c1c[n](-c(cccc2Cl)c2F)nn1)=O LNKXXEMOPNVZGM-UHFFFAOYSA-N 0.000 description 1
- NGVXSPZNILPQBM-UHFFFAOYSA-N NC(c(cc1)ccc1NC(C(c1c(CC2)c(N(CC3)CCC3N(CCC3)C3=O)ccc1)N2C(c1c[n](-c(cccc2Cl)c2F)nn1)=O)=O)=O Chemical compound NC(c(cc1)ccc1NC(C(c1c(CC2)c(N(CC3)CCC3N(CCC3)C3=O)ccc1)N2C(c1c[n](-c(cccc2Cl)c2F)nn1)=O)=O)=O NGVXSPZNILPQBM-UHFFFAOYSA-N 0.000 description 1
- YTULCQGNUIGFGU-UHFFFAOYSA-N NCc1cccc(C2C(Nc(cc3)ccc3C(O)=O)=O)c1CCN2C(c1c[n](-c(cccc2Cl)c2F)nn1)=O Chemical compound NCc1cccc(C2C(Nc(cc3)ccc3C(O)=O)=O)c1CCN2C(c1c[n](-c(cccc2Cl)c2F)nn1)=O YTULCQGNUIGFGU-UHFFFAOYSA-N 0.000 description 1
- AKPYALCPZPVVAN-UHFFFAOYSA-N OC(C(C1)ON=C1c(c(F)c(cc1)Cl)c1F)=O Chemical compound OC(C(C1)ON=C1c(c(F)c(cc1)Cl)c1F)=O AKPYALCPZPVVAN-UHFFFAOYSA-N 0.000 description 1
- DTPSCOKGXYBDJF-UHFFFAOYSA-N OC(C(CC1=O)CN1c1cccc(Cl)c1F)=O Chemical compound OC(C(CC1=O)CN1c1cccc(Cl)c1F)=O DTPSCOKGXYBDJF-UHFFFAOYSA-N 0.000 description 1
- OHZPVCRHBZYZJT-UHFFFAOYSA-N OC(c(cc1)ccc1NC(C(c1c(CC2)c(N(CC3)CCC3N(CCC3)C3=O)ccc1)N2C(c(nc1)c[n]1-c(cccc1Cl)c1F)=O)=O)=O Chemical compound OC(c(cc1)ccc1NC(C(c1c(CC2)c(N(CC3)CCC3N(CCC3)C3=O)ccc1)N2C(c(nc1)c[n]1-c(cccc1Cl)c1F)=O)=O)=O OHZPVCRHBZYZJT-UHFFFAOYSA-N 0.000 description 1
- AMHCONOGPXXSHI-UHFFFAOYSA-N OC(c(cc1)ccc1NC(C(c1c(CC2)c(OC3COC3)ccc1)N2C(c1c[n](-c2cccc(Cl)c2F)nn1)=O)=O)=O Chemical compound OC(c(cc1)ccc1NC(C(c1c(CC2)c(OC3COC3)ccc1)N2C(c1c[n](-c2cccc(Cl)c2F)nn1)=O)=O)=O AMHCONOGPXXSHI-UHFFFAOYSA-N 0.000 description 1
- OFIYZOXNLSDWIA-XRKRLSELSA-N OC(c(cc1)ccc1NC([C@@H](c1c(CC2)c(N3CCN(CC(F)(F)F)CC3)ccc1)N2C([C@@H](C1)ON=C1c(cccc1Cl)c1F)=O)=O)=O Chemical compound OC(c(cc1)ccc1NC([C@@H](c1c(CC2)c(N3CCN(CC(F)(F)F)CC3)ccc1)N2C([C@@H](C1)ON=C1c(cccc1Cl)c1F)=O)=O)=O OFIYZOXNLSDWIA-XRKRLSELSA-N 0.000 description 1
- HRLKIYSEPAYSAH-HSZRJFAPSA-N OC(c(cc1)ccc1NC([C@@H](c1ccccc1CC1)N1C(c1c[n](-c(cccc2Cl)c2F)nn1)=O)=O)=O Chemical compound OC(c(cc1)ccc1NC([C@@H](c1ccccc1CC1)N1C(c1c[n](-c(cccc2Cl)c2F)nn1)=O)=O)=O HRLKIYSEPAYSAH-HSZRJFAPSA-N 0.000 description 1
- QWULNBLKJBJATC-BHYZAODMSA-N OC(c(cc1)ccc1NC([C@H](c1c(CC2)c(N(CC3)CCC3C3COC3)ccc1)N2C([C@@H](C1)ON=C1c(cccc1Cl)c1F)=O)=O)=O Chemical compound OC(c(cc1)ccc1NC([C@H](c1c(CC2)c(N(CC3)CCC3C3COC3)ccc1)N2C([C@@H](C1)ON=C1c(cccc1Cl)c1F)=O)=O)=O QWULNBLKJBJATC-BHYZAODMSA-N 0.000 description 1
- UCSKYPRDSCVAMS-MHZLTWQESA-N OC(c(cc1)ccc1NC([C@H](c1c(CC2)c(N3CCOCC3)ccc1)N2C(c1c[n](-c(cccc2Cl)c2F)nn1)=O)=O)=O Chemical compound OC(c(cc1)ccc1NC([C@H](c1c(CC2)c(N3CCOCC3)ccc1)N2C(c1c[n](-c(cccc2Cl)c2F)nn1)=O)=O)=O UCSKYPRDSCVAMS-MHZLTWQESA-N 0.000 description 1
- JQEHHXASFNDRCX-UHFFFAOYSA-N OC(c1c[o]c(-c(cccc2Cl)c2F)n1)=O Chemical compound OC(c1c[o]c(-c(cccc2Cl)c2F)n1)=O JQEHHXASFNDRCX-UHFFFAOYSA-N 0.000 description 1
- NYQZRXFSTDWBHC-UHFFFAOYSA-N OCCNc1cccc(C2C(Nc(cc3)ccc3C(O)=O)=O)c1CCN2C(c1c[n](-c(cccc2Cl)c2F)nn1)=O Chemical compound OCCNc1cccc(C2C(Nc(cc3)ccc3C(O)=O)=O)c1CCN2C(c1c[n](-c(cccc2Cl)c2F)nn1)=O NYQZRXFSTDWBHC-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
-
- 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
- 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
- C07D401/06—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 only aliphatic carbon atoms
-
- 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
- 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
- C07D405/14—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 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 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
- C07D471/10—Spiro-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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
Landscapes
- 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)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361804883P | 2013-03-25 | 2013-03-25 | |
| US61/804,883 | 2013-03-25 | ||
| US201361840736P | 2013-06-28 | 2013-06-28 | |
| US61/840,736 | 2013-06-28 | ||
| US201361894607P | 2013-10-23 | 2013-10-23 | |
| US61/894,607 | 2013-10-23 | ||
| PCT/US2014/031651 WO2014160668A1 (en) | 2013-03-25 | 2014-03-25 | Tetrahydroisoquinolines containing substituted azoles as factor xia inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016519096A JP2016519096A (ja) | 2016-06-30 |
| JP2016519096A5 JP2016519096A5 (https=) | 2017-04-13 |
| JP6479763B2 true JP6479763B2 (ja) | 2019-03-06 |
Family
ID=50487219
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016505527A Expired - Fee Related JP6479763B2 (ja) | 2013-03-25 | 2014-03-25 | 第xia因子阻害剤としての置換アゾール含有のテトラヒドロイソキノリン |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US9738655B2 (https=) |
| EP (1) | EP2978751B1 (https=) |
| JP (1) | JP6479763B2 (https=) |
| CN (1) | CN105228996B (https=) |
| ES (1) | ES2712699T3 (https=) |
| WO (1) | WO2014160668A1 (https=) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101937514B1 (ko) | 2011-10-14 | 2019-01-10 | 브리스톨-마이어스 스큅 컴퍼니 | 인자 xia 억제제로서의 치환된 테트라히드로이소퀴놀린 화합물 |
| EP2906552B1 (en) | 2012-10-12 | 2017-11-22 | Bristol-Myers Squibb Company | Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| WO2014059214A1 (en) | 2012-10-12 | 2014-04-17 | Bristol-Myers Squibb Company | Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| TR201807316T4 (tr) | 2012-10-12 | 2018-06-21 | Bristol Myers Squibb Co | Bir faktör XIa inhibitörünün kristalli formları. |
| GB201314286D0 (en) * | 2013-08-08 | 2013-09-25 | Takeda Pharmaceutical | Therapeutic Compounds |
| NO2760821T3 (https=) | 2014-01-31 | 2018-03-10 | ||
| CN116987080A (zh) | 2014-01-31 | 2023-11-03 | 百时美施贵宝公司 | 作为因子xia抑制剂的具有杂环p2′基团的大环化合物 |
| 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 |
| US10117864B2 (en) * | 2015-03-18 | 2018-11-06 | Bayer Pharma Aktiengesellschaft | Substituted N-bicyclo-2-aryl-quinolin-4-carboxamides and use thereof |
| CN105541716B (zh) * | 2015-03-26 | 2024-02-23 | Agc株式会社 | 吡唑衍生物的制造方法 |
| WO2016205482A1 (en) | 2015-06-19 | 2016-12-22 | Bristol-Myers Squibb Company | Diamide macrocycles as factor xia inhibitors |
| US10287288B2 (en) | 2015-07-29 | 2019-05-14 | Bristol-Myers Squibb | Factor XIa macrocyclic inhibitors bearing alkyl or cycloalkyl P2' moieties |
| ES2871111T3 (es) | 2015-07-29 | 2021-10-28 | Bristol Myers Squibb Co | Inhibidores macrocíclicos del factor XIa que contienen un grupo P2' no aromático |
| WO2017074833A1 (en) | 2015-10-29 | 2017-05-04 | Merck Sharp & Dohme Corp. | Macrocyclic spirocarbamate derivatives as factor xia inhibitors, pharmaceutically acceptable compositions and their use |
| 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 |
| EP3500556B1 (en) | 2016-08-22 | 2023-08-02 | Merck Sharp & Dohme LLC | Pyridine-1-oxide derivatives and their use as factor xia inhibitors |
| EP3541381B1 (en) * | 2016-11-18 | 2022-12-28 | Merck Sharp & Dohme LLC | Inhibitors of factor xiia |
| 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 |
| EP3778597B1 (en) * | 2018-03-28 | 2025-05-28 | Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. | Tetrahydroisoquinoline derivative, preparation method therefor and uses thereof |
| WO2019218899A1 (zh) * | 2018-05-17 | 2019-11-21 | 四川科伦博泰生物医药股份有限公司 | 含聚乙二醇醚的四氢异喹啉酰胺化合物及其药物用途 |
| WO2020259668A1 (zh) * | 2019-06-28 | 2020-12-30 | 上海济煜医药科技有限公司 | 三并环类化合物及其制备方法和用途 |
| CN113004286B (zh) * | 2019-12-20 | 2022-08-12 | 成都康弘药业集团股份有限公司 | 作为血浆激肽释放酶抑制剂的三环类化合物及其用途 |
| CN115066417B (zh) * | 2019-12-31 | 2025-05-02 | 上海京新生物医药有限公司 | 凝血因子XIa抑制剂 |
| KR20230110544A (ko) * | 2020-11-19 | 2023-07-24 | 머크 샤프 앤드 돔 엘엘씨 | 혈장 칼리크레인 억제제 |
| US20240000769A1 (en) * | 2020-12-18 | 2024-01-04 | UCB Biopharma SRL | Amorphous solid dispersions |
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| CN105228996B (zh) | 2017-11-28 |
| EP2978751A1 (en) | 2016-02-03 |
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