JP6892858B2 - 第ＸＩａ因子阻害剤 - Google Patents
第ＸＩａ因子阻害剤 Download PDFInfo
- Publication number
- JP6892858B2 JP6892858B2 JP2018521211A JP2018521211A JP6892858B2 JP 6892858 B2 JP6892858 B2 JP 6892858B2 JP 2018521211 A JP2018521211 A JP 2018521211A JP 2018521211 A JP2018521211 A JP 2018521211A JP 6892858 B2 JP6892858 B2 JP 6892858B2
- Authority
- JP
- Japan
- Prior art keywords
- mmol
- mixture
- alkyl
- stirred
- halo
- 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.)
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Links
- 0 *=S(CC1C(CC(O)=O)C1)(*=O)c1nc2ccccc2[s]1 Chemical compound *=S(CC1C(CC(O)=O)C1)(*=O)c1nc2ccccc2[s]1 0.000 description 19
- FQMMQJVVXMEVMK-UHFFFAOYSA-N CC1(C)OB(C(C#CC(C=C2)Cl)=C2c2cnc[o]2)OC1(C)C Chemical compound CC1(C)OB(C(C#CC(C=C2)Cl)=C2c2cnc[o]2)OC1(C)C FQMMQJVVXMEVMK-UHFFFAOYSA-N 0.000 description 1
- OTVHUEBCKRVBIT-UHFFFAOYSA-N CC1(C)OB(c(c(F)ccc2Cl)c2F)OC1(C)C Chemical compound CC1(C)OB(c(c(F)ccc2Cl)c2F)OC1(C)C OTVHUEBCKRVBIT-UHFFFAOYSA-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
- C07D401/14—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- 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
-
- 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
- C07D401/04—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 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
- C07D413/14—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
- C07D471/08—Bridged 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
- 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
- C07D487/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562248075P | 2015-10-29 | 2015-10-29 | |
| US62/248,075 | 2015-10-29 | ||
| PCT/US2016/058362 WO2017074832A1 (en) | 2015-10-29 | 2016-10-24 | FACTOR XIa INHIBITORS |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018531954A JP2018531954A (ja) | 2018-11-01 |
| JP2018531954A5 JP2018531954A5 (enExample) | 2019-11-28 |
| JP6892858B2 true JP6892858B2 (ja) | 2021-06-23 |
Family
ID=58631804
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018521211A Active JP6892858B2 (ja) | 2015-10-29 | 2016-10-24 | 第ＸＩａ因子阻害剤 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US10214512B2 (enExample) |
| EP (1) | EP3368036B1 (enExample) |
| JP (1) | JP6892858B2 (enExample) |
| KR (1) | KR102727485B1 (enExample) |
| CN (1) | CN108430471B (enExample) |
| AU (1) | AU2016344476B2 (enExample) |
| BR (1) | BR112018008506B8 (enExample) |
| CA (1) | CA2998902C (enExample) |
| MA (1) | MA43128A (enExample) |
| MX (1) | MX387515B (enExample) |
| RU (1) | RU2728783C2 (enExample) |
| WO (1) | WO2017074832A1 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3870171B1 (en) * | 2018-10-25 | 2024-11-20 | Merck Sharp & Dohme LLC | Factor xia inhibitors |
| ES2974842T3 (es) * | 2018-11-13 | 2024-07-01 | Novartis Ag | Compuestos y composiciones para el tratamiento de afecciones asociadas a la actividad de nlrp |
| EP3957638B1 (en) | 2019-04-16 | 2025-01-08 | China Resources Biopharmaceutical Company Limited | Macrocyclic derivatives acting as xia factor inhibitor |
| US20220281868A1 (en) | 2019-07-23 | 2022-09-08 | Medshine Discovery Inc. | Macrocyclic derivatives as factor xia inhibitors |
| JP7773522B2 (ja) * | 2020-07-10 | 2025-11-19 | メルク・シャープ・アンド・ドーム・エルエルシー | 血漿カリクレイン阻害薬 |
| US12497403B2 (en) | 2021-01-28 | 2025-12-16 | Merck Sharp & Dohme Llc | Factor XIa inhibitors |
| US11845748B2 (en) | 2021-03-18 | 2023-12-19 | Janssen Pharmaceutica Nv | Bicyclic pyridine N-oxide derivatives useful as a factor XIa inhibitors |
| US11814364B2 (en) | 2021-03-18 | 2023-11-14 | Janssen Pharmaceutica Nv | Pyridine N-oxide derivatives useful as factor XIa inhibitors |
| US11919881B2 (en) | 2021-03-18 | 2024-03-05 | Janssen Pharmaceutica Nv | Substituted pyridine N-oxide derivatives useful as a factor XIa inhibitors |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002227269A1 (en) | 2000-11-07 | 2002-06-03 | Bristol-Myers Squibb Company | Acid derivatives useful as serine protease inhibitors |
| WO2002037937A2 (en) | 2000-11-07 | 2002-05-16 | Bristol-Myers Squibb Company | Acid derivatives useful as serine protease inhibitors |
| WO2002060894A2 (en) | 2001-01-30 | 2002-08-08 | Bristol-Myers Squibb Company | Sulfonamide lactam inhibitors of factor xa |
| US6825208B2 (en) | 2001-08-20 | 2004-11-30 | Bristol-Myers Squibb Pharma Company | Tetrahydroquinoline derivatives as antithrombotic agents |
| WO2004002405A2 (en) | 2002-06-26 | 2004-01-08 | Bristol-Myers Squibb Company | Amino-bicyclic pyrazinones and pyridinones |
| US20040180855A1 (en) | 2003-02-19 | 2004-09-16 | Schumacher William A. | Methods of treating thrombosis with reduced risk of increased bleeding times |
| US7138412B2 (en) | 2003-03-11 | 2006-11-21 | Bristol-Myers Squibb Company | Tetrahydroquinoline derivatives useful as serine protease inhibitors |
| US7129264B2 (en) | 2003-04-16 | 2006-10-31 | Bristol-Myers Squibb Company | Biarylmethyl indolines and indoles as antithromboembolic agents |
| US7417063B2 (en) | 2004-04-13 | 2008-08-26 | Bristol-Myers Squibb Company | Bicyclic heterocycles useful as serine protease inhibitors |
| US7429604B2 (en) | 2004-06-15 | 2008-09-30 | Bristol Myers Squibb Company | Six-membered heterocycles useful as serine protease inhibitors |
| US7453002B2 (en) | 2004-06-15 | 2008-11-18 | Bristol-Myers Squibb Company | Five-membered heterocycles useful as serine protease inhibitors |
| US20060074103A1 (en) | 2004-10-06 | 2006-04-06 | Corte James R | Cyclic beta-amino acid derivatives as factor Xa inhibitors |
| EP1828152B1 (en) | 2004-12-08 | 2008-08-20 | Bristol-Myers Squibb Company | Heterocyclic compounds as inhibitors of factor viia |
| TW200637843A (en) | 2005-01-10 | 2006-11-01 | Bristol Myers Squibb Co | Phenylglycinamide derivatives useful as anticoagulants |
| EP1841504B1 (en) | 2005-01-13 | 2014-11-19 | Bristol-Myers Squibb Company | Substituted biaryl compounds as factor xia inhibitors |
| WO2006089005A2 (en) | 2005-02-17 | 2006-08-24 | Bristol-Myers Squibb Company | Combination of selective factor viia and/or xia and plasma kallikrein inhibitors |
| CN101228129A (zh) * | 2005-04-20 | 2008-07-23 | 詹森药业有限公司 | 氟代吡啶n-氧化物凝血酶调节剂和含氮杂芳基化合物的n-氧化方法 |
| WO2007070816A2 (en) | 2005-12-14 | 2007-06-21 | Bristol-Myers Squibb Company | Thiophene derivatives as factor xia inhibitors |
| EA014245B1 (ru) | 2005-12-14 | 2010-10-29 | Бристол-Маерс Сквибб Компани | Аналоги арилпропионамида, арилакриламида, арилпропинамида или арилметилмочевины в качестве ингибиторов фактора xia |
| JP2009519966A (ja) | 2005-12-14 | 2009-05-21 | ブリストル−マイヤーズ スクイブ カンパニー | セリンプロテアーゼ阻害剤として有用な６員ヘテロ環 |
| WO2007109459A2 (en) * | 2006-03-21 | 2007-09-27 | Janssen Pharmaceutica, Nv | Pyridines and pyridine n-oxides as modulators of thrombin |
| ES2546815T3 (es) | 2006-12-15 | 2015-09-28 | Bristol-Myers Squibb Company | Análogos de arilpropilamida, arilacrilamida, arilpropinamida o arilmetilurea como inhibidores del factor XIa |
| PE20091002A1 (es) * | 2007-06-13 | 2009-07-15 | Bristol Myers Squibb Co | Analogos dipeptidos como inhibidores del factor de coagulacion |
| WO2009114677A1 (en) | 2008-03-13 | 2009-09-17 | Bristol-Myers Squibb Company | Pyridazine derivatives as factor xia inhibitors |
| WO2011100401A1 (en) | 2010-02-11 | 2011-08-18 | Bristol-Myers Squibb Company | Macrocycles as factor xia inhibitors |
| 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 |
| CN103987697B (zh) | 2011-10-14 | 2017-04-26 | 百时美施贵宝公司 | 作为因子xia抑制剂的取代的四氢异喹啉化合物 |
| CN103987696B (zh) | 2011-10-14 | 2016-12-21 | 百时美施贵宝公司 | 作为因子xia抑制剂的取代的四氢异喹啉化合物 |
| PH12014500625B1 (en) | 2011-10-14 | 2018-12-12 | Bristol Myers Squibb Co | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| IN2014CN04676A (enExample) | 2011-12-21 | 2015-09-18 | Ono Pharmaceutical Co | |
| JP2015083542A (ja) | 2012-02-08 | 2015-04-30 | 大日本住友製薬株式会社 | ３位置換プロリン誘導体 |
| HRP20161378T1 (hr) * | 2012-08-03 | 2016-12-02 | Bristol-Myers Squibb Company | Dihidropiridon kao faktor xia inhibitora |
| HUE032622T2 (en) * | 2012-08-03 | 2017-10-30 | Bristol Myers Squibb Co | Dihydropyridone p1 as factor xia inhibitors |
| WO2014160592A2 (en) | 2013-03-27 | 2014-10-02 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
| SG10201908467RA (en) * | 2014-01-31 | 2019-10-30 | Bristol Myers Squibb Co | Macrocycles with hetrocyclic p2' groups as factor xia inhibitors |
| NO2760821T3 (enExample) * | 2014-01-31 | 2018-03-10 | ||
| EP3104701B1 (en) * | 2014-02-11 | 2019-01-30 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
| US20150291609A1 (en) * | 2014-04-11 | 2015-10-15 | The University Of North Carolina At Chapel Hill | Mertk-specific pyrimidine compounds |
| US9453018B2 (en) * | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
| US20180162821A1 (en) * | 2016-12-14 | 2018-06-14 | Bristol-Myers Squibb Company | Factor xia macrocycles with novel p1 groups |
-
2016
- 2016-10-24 US US15/771,538 patent/US10214512B2/en active Active
- 2016-10-24 MX MX2018005045A patent/MX387515B/es unknown
- 2016-10-24 WO PCT/US2016/058362 patent/WO2017074832A1/en not_active Ceased
- 2016-10-24 AU AU2016344476A patent/AU2016344476B2/en active Active
- 2016-10-24 MA MA043128A patent/MA43128A/fr unknown
- 2016-10-24 JP JP2018521211A patent/JP6892858B2/ja active Active
- 2016-10-24 KR KR1020187013433A patent/KR102727485B1/ko active Active
- 2016-10-24 CN CN201680059577.7A patent/CN108430471B/zh active Active
- 2016-10-24 CA CA2998902A patent/CA2998902C/en active Active
- 2016-10-24 RU RU2018119015A patent/RU2728783C2/ru active
- 2016-10-24 BR BR112018008506A patent/BR112018008506B8/pt active IP Right Grant
- 2016-10-24 EP EP16860556.6A patent/EP3368036B1/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| AU2016344476A1 (en) | 2018-03-08 |
| RU2728783C2 (ru) | 2020-07-31 |
| RU2018119015A (ru) | 2019-11-29 |
| AU2016344476B2 (en) | 2020-08-13 |
| EP3368036A4 (en) | 2019-04-17 |
| KR20180073602A (ko) | 2018-07-02 |
| MA43128A (fr) | 2018-09-05 |
| EP3368036B1 (en) | 2022-07-20 |
| MX2018005045A (es) | 2018-08-01 |
| CA2998902A1 (en) | 2017-05-04 |
| US10214512B2 (en) | 2019-02-26 |
| JP2018531954A (ja) | 2018-11-01 |
| CA2998902C (en) | 2024-03-26 |
| MX387515B (es) | 2025-03-18 |
| BR112018008506A2 (pt) | 2018-10-23 |
| BR112018008506B8 (pt) | 2023-12-05 |
| RU2018119015A3 (enExample) | 2020-02-18 |
| EP3368036A1 (en) | 2018-09-05 |
| WO2017074832A1 (en) | 2017-05-04 |
| CN108430471A (zh) | 2018-08-21 |
| CN108430471B (zh) | 2021-07-09 |
| BR112018008506B1 (pt) | 2023-11-14 |
| US20180339977A1 (en) | 2018-11-29 |
| KR102727485B1 (ko) | 2024-11-06 |
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