JP6033317B2 - 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 - Google Patents
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 Download PDFInfo
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- JP6033317B2 JP6033317B2 JP2014535894A JP2014535894A JP6033317B2 JP 6033317 B2 JP6033317 B2 JP 6033317B2 JP 2014535894 A JP2014535894 A JP 2014535894A JP 2014535894 A JP2014535894 A JP 2014535894A JP 6033317 B2 JP6033317 B2 JP 6033317B2
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- Prior art keywords
- alkyl
- phenyl
- group
- chloro
- acryloyl
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- 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 CCN(C(C(N*)=O)C1=S2(*)(CC2)CCCCCC1)C(C)=O Chemical compound CCN(C(C(N*)=O)C1=S2(*)(CC2)CCCCCC1)C(C)=O 0.000 description 5
- LWNZPXFPMLRKGK-UHFFFAOYSA-N CC(C)(C)OC(N(CCN1c2c(CCN=C3)c3ccc2)CC1=O)=O Chemical compound CC(C)(C)OC(N(CCN1c2c(CCN=C3)c3ccc2)CC1=O)=O LWNZPXFPMLRKGK-UHFFFAOYSA-N 0.000 description 1
- UUJNHTZCROBQHX-UHFFFAOYSA-N CC(C)C(NCCc1ccccc1)=O Chemical compound CC(C)C(NCCc1ccccc1)=O UUJNHTZCROBQHX-UHFFFAOYSA-N 0.000 description 1
- QHQKYJAIOSKSFL-UHFFFAOYSA-N CC(C)C(NCc1ccccc1)=O Chemical compound CC(C)C(NCc1ccccc1)=O QHQKYJAIOSKSFL-UHFFFAOYSA-N 0.000 description 1
- UIKJRDSCEYGECG-UHFFFAOYSA-N CC(C)C(OCc1ccccc1)=O Chemical compound CC(C)C(OCc1ccccc1)=O UIKJRDSCEYGECG-UHFFFAOYSA-N 0.000 description 1
- LMTGCJANOQOGPI-UHFFFAOYSA-N CC(N(C)c1ccccc1)=O Chemical compound CC(N(C)c1ccccc1)=O LMTGCJANOQOGPI-UHFFFAOYSA-N 0.000 description 1
- XVAIDCNLVLTVFM-UHFFFAOYSA-N CC(Nc(cc1)ccc1OC)=O Chemical compound CC(Nc(cc1)ccc1OC)=O XVAIDCNLVLTVFM-UHFFFAOYSA-N 0.000 description 1
- XWSRKIHDBLVVQU-UHFFFAOYSA-N CCC(Nc1ccc(C)cc1)=O Chemical compound CCC(Nc1ccc(C)cc1)=O XWSRKIHDBLVVQU-UHFFFAOYSA-N 0.000 description 1
- FVTFRNFJCGAMRS-MJZVOSTQSA-N COC(NCc(cc1)ccc1NC([C@H](c1c(CC2)cccc1)N2C(/C=C/c1cc(Cl)ccc1-[n]1nnnc1)=O)=O)=O Chemical compound COC(NCc(cc1)ccc1NC([C@H](c1c(CC2)cccc1)N2C(/C=C/c1cc(Cl)ccc1-[n]1nnnc1)=O)=O)=O FVTFRNFJCGAMRS-MJZVOSTQSA-N 0.000 description 1
- QYGIONMGVBWAHW-XNWCZRBMSA-N COC(Nc(cc1)ccc1NC(C(c1c(CC2)nc[nH]1)N2C(/C=C/c1cc(Cl)ccc1-[n]1nnnc1)=O)=O)=O Chemical compound COC(Nc(cc1)ccc1NC(C(c1c(CC2)nc[nH]1)N2C(/C=C/c1cc(Cl)ccc1-[n]1nnnc1)=O)=O)=O QYGIONMGVBWAHW-XNWCZRBMSA-N 0.000 description 1
- GVQIGVXVWBEQBR-NYYWCZLTSA-N COCCOc1cc(CCN(C2C(Nc(cc3)ccc3C(O)=O)=O)C(/C=C/c(cc(cc3)Cl)c3-[n]3nnnc3)=O)c2cc1 Chemical compound COCCOc1cc(CCN(C2C(Nc(cc3)ccc3C(O)=O)=O)C(/C=C/c(cc(cc3)Cl)c3-[n]3nnnc3)=O)c2cc1 GVQIGVXVWBEQBR-NYYWCZLTSA-N 0.000 description 1
- FNJYORJOJJSXMG-BJMVGYQFSA-N Cc1n[n](C)c(CC2)c1C(C(Nc(cc1)cc(CC3)c1NC3=O)=O)N2C(/C=C/c(c(-[n]1nnnc1)ccc1Cl)c1F)=O Chemical compound Cc1n[n](C)c(CC2)c1C(C(Nc(cc1)cc(CC3)c1NC3=O)=O)N2C(/C=C/c(c(-[n]1nnnc1)ccc1Cl)c1F)=O FNJYORJOJJSXMG-BJMVGYQFSA-N 0.000 description 1
- BOJKOKSDOYFFOO-KZLCEWNNSA-N OC(c(cc1)ccc1NC([C@H](c(cc1)c(CC2)cc1OCc1ccccc1)N2C(/C=C/c1cc(Cl)ccc1-[n]1nnnc1)=O)=O)=O Chemical compound OC(c(cc1)ccc1NC([C@H](c(cc1)c(CC2)cc1OCc1ccccc1)N2C(/C=C/c1cc(Cl)ccc1-[n]1nnnc1)=O)=O)=O BOJKOKSDOYFFOO-KZLCEWNNSA-N 0.000 description 1
- XLVCNINDJUKQNE-FRHHVXPKSA-N OC(c(cc1)ccc1NC([C@H](c1c(CC2)cccc1)N2C(/C=C/c1cc(Cl)ccc1-[n]1nnnc1)=O)=O)=O Chemical compound OC(c(cc1)ccc1NC([C@H](c1c(CC2)cccc1)N2C(/C=C/c1cc(Cl)ccc1-[n]1nnnc1)=O)=O)=O XLVCNINDJUKQNE-FRHHVXPKSA-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)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (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 | |
US61/547,305 | 2011-10-14 | ||
PCT/US2012/059859 WO2013055984A1 (en) | 2011-10-14 | 2012-10-12 | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2014528479A JP2014528479A (ja) | 2014-10-27 |
JP2014528479A5 JP2014528479A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2015-12-03 |
JP6033317B2 true JP6033317B2 (ja) | 2016-11-30 |
Family
ID=47080862
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014535894A Expired - Fee Related JP6033317B2 (ja) | 2011-10-14 | 2012-10-12 | 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 |
Country Status (7)
Families Citing this family (54)
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CN102753555B (zh) | 2010-02-11 | 2018-01-12 | 百时美施贵宝公司 | 作为因子xia抑制剂的大环类 |
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 |
TWI633091B (zh) | 2011-10-14 | 2018-08-21 | Bristol-Myers Squibb Company | 作為因子xia抑制劑之經取代四氫異喹啉化合物 |
ES2699226T3 (es) | 2011-10-14 | 2019-02-08 | Bristol Myers Squibb Co | Compuestos de tetrahidroisoquinolina sustituidos como inhibidores del factor XIa |
ES2579832T3 (es) | 2011-10-14 | 2016-08-17 | Bristol-Myers Squibb Company | Compuestos de tetrahidroisoquinolina sustituida como inhibidores del factor XIa |
EA028581B1 (ru) | 2012-08-03 | 2017-12-29 | Бристол-Маерс Сквибб Компани | ДИГИДРОПИРИДОН Р1 В КАЧЕСТВЕ ИНГИБИТОРОВ ФАКТОРА XIa |
HUE031582T2 (en) | 2012-08-03 | 2017-07-28 | Bristol Myers Squibb Co | Dihydropyridone as factor xia inhibitors |
EP2906541B1 (en) * | 2012-10-12 | 2017-11-22 | Bristol-Myers Squibb Company | Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
US9315519B2 (en) | 2012-10-12 | 2016-04-19 | Bristol-Myers Squibb Company | Guanidine 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. |
JP6280912B2 (ja) | 2013-03-14 | 2018-02-14 | 武田薬品工業株式会社 | 複素環化合物 |
WO2014160668A1 (en) | 2013-03-25 | 2014-10-02 | Bristol-Myers Squibb Company | Tetrahydroisoquinolines containing substituted azoles as factor xia inhibitors |
WO2015002231A1 (ja) | 2013-07-03 | 2015-01-08 | 武田薬品工業株式会社 | 複素環化合物 |
US10472376B2 (en) | 2013-07-03 | 2019-11-12 | Takeda Pharmaceutical Company Limited | Amide compound |
US20160229839A1 (en) * | 2013-09-27 | 2016-08-11 | Merck Sharp & Dohme Corp. | Factor XIa Inhibitors |
US20160257668A1 (en) * | 2013-10-07 | 2016-09-08 | Merck Sharp & Dohme Corp. | Factor XIa Inhibitors |
NO2760821T3 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2014-01-31 | 2018-03-10 | ||
DK3099687T3 (en) | 2014-01-31 | 2018-10-22 | Bristol Myers Squibb Co | MACROCYCLES WITH HETEROCYCLIC P2 'GROUPS AS FACTOR XIA INHIBITORS |
US9944643B2 (en) | 2014-02-11 | 2018-04-17 | Merck Sharp & Dohme Corp. | Factor XIa inhibitors |
US9676723B2 (en) | 2014-02-11 | 2017-06-13 | Merck Sharp & Dohme Corp | Factor XIa inhibitors |
US10093683B2 (en) | 2014-04-22 | 2018-10-09 | Merck Sharp & Dohme Corp. | Factor XIa inhibitors |
CN111728970A (zh) * | 2014-05-16 | 2020-10-02 | 坎伯兰医药品股份有限公司 | 用伊非曲班治疗心脏纤维化的组合物和方法 |
JP6611363B2 (ja) * | 2014-07-01 | 2019-11-27 | 武田薬品工業株式会社 | 複素環化合物およびRetinoid−related Orphan Receptor(ROR)ガンマーT阻害剤としてのそれらの使用 |
EP3180317B1 (en) | 2014-07-28 | 2021-04-14 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
MY187540A (en) * | 2014-08-01 | 2021-09-28 | Nuevolution As | Compounds active towards bromodomains |
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 |
ES2714283T3 (es) | 2014-09-04 | 2019-05-28 | Bristol Myers Squibb Co | Macrociclos de diamida que son inhibidores de FXIa |
US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
CN106715473B (zh) | 2014-10-01 | 2021-11-23 | 免疫医疗有限公司 | 替格瑞洛的抗体及其使用方法 |
EP3310777B1 (en) | 2015-06-19 | 2019-10-09 | Bristol-Myers Squibb Company | Diamide macrocycles as factor xia inhibitors |
US20170000771A1 (en) | 2015-06-30 | 2017-01-05 | Cumberland Pharmaceuticals, Inc. | Thromboxane Receptor Antagonists in AERD/Asthma |
WO2017007756A1 (en) | 2015-07-06 | 2017-01-12 | Rodin Therapeutics, Inc | Hetero-halo inhibitors of histone deacetylase |
EP3319968A1 (en) | 2015-07-06 | 2018-05-16 | Rodin Therapeutics, Inc. | Heterobicyclic n-aminophenyl-amides as inhibitors of histone deacetylase |
EP3328851B1 (en) | 2015-07-29 | 2020-04-22 | Bristol-Myers Squibb Company | Factor xia macrocyclic inhibitors bearing alkyl or cycloalkyl p2' moieties |
EP3868753B1 (en) | 2015-07-29 | 2022-12-21 | Bristol-Myers Squibb Company | Factor xia macrocyclic inhibitors bearing a non-aromatic p2' group |
US10344039B2 (en) | 2015-10-29 | 2019-07-09 | Merck Sharp & Dohme Corp. | Macrocyclic spirocarbamate derivatives as factor XIa inhibitors, pharmaceutically acceptable compositions and their use |
EP3368036B1 (en) | 2015-10-29 | 2022-07-20 | Merck Sharp & Dohme LLC | Macrocyclic pyridine-n-oxide derivatives as factor xia inhibitors |
JP6964343B2 (ja) | 2015-11-20 | 2021-11-10 | フォーマ セラピューティクス,インコーポレイテッド | ユビキチン特異的プロテアーゼ1阻害剤としてのプリノン |
US11480559B2 (en) * | 2016-01-07 | 2022-10-25 | Fujimori Kogyo Co., Ltd. | Blood collection tube, reagent, and method for analyzing blood characteristics using same |
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CN111032040B (zh) | 2017-08-07 | 2023-08-29 | 罗丹疗法公司 | 组蛋白去乙酰酶的双环抑制剂 |
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 |
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CN111727186B (zh) * | 2018-11-11 | 2022-11-08 | 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 |
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EP2766345A1 (en) | 2014-08-20 |
US20160289209A1 (en) | 2016-10-06 |
EP2766345B1 (en) | 2016-03-16 |
CN103987697B (zh) | 2017-04-26 |
EP2899183A1 (en) | 2015-07-29 |
IN2014CN02806A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2015-07-03 |
ES2572908T3 (es) | 2016-06-03 |
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US10906886B2 (en) | 2021-02-02 |
US10000466B2 (en) | 2018-06-19 |
US9108951B2 (en) | 2015-08-18 |
US20170305880A1 (en) | 2017-10-26 |
WO2013055984A1 (en) | 2013-04-18 |
ES2699226T3 (es) | 2019-02-08 |
US20140275061A1 (en) | 2014-09-18 |
JP2014528479A (ja) | 2014-10-27 |
CN103987697A (zh) | 2014-08-13 |
US9725435B2 (en) | 2017-08-08 |
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