TW201319068A - 作為ｘｉａ因子抑制劑之環狀ｐ１接合劑 - Google Patents

作為ｘｉａ因子抑制劑之環狀ｐ１接合劑 Download PDF

Info

Publication number
TW201319068A
TW201319068A TW101128158A TW101128158A TW201319068A TW 201319068 A TW201319068 A TW 201319068A TW 101128158 A TW101128158 A TW 101128158A TW 101128158 A TW101128158 A TW 101128158A TW 201319068 A TW201319068 A TW 201319068A
Authority
TW
Taiwan
Prior art keywords
group
alkyl
mmol
etoac
compound
Prior art date
Application number
TW101128158A
Other languages
English (en)
Chinese (zh)
Inventor
查理斯Ｇ 克拉克
詹姆士Ｒ 柯德
威廉Ｒ 艾文
保羅Ｊ 吉理甘
鐘允
派翠克Ｙ Ｓ 蘭
楊武
黎爾Ｍ 二世 史密斯
王裕豐
Original Assignee
必治妥美雅史谷比公司
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 必治妥美雅史谷比公司 filed Critical 必治妥美雅史谷比公司
Publication of TW201319068A publication Critical patent/TW201319068A/zh

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/08—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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
    • 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
    • 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
    • C07D471/06—Peri-condensed systems
    • 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
    • C07D487/06—Peri-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
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/06—Peri-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • 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)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
TW101128158A 2011-08-05 2012-08-03 作為ｘｉａ因子抑制劑之環狀ｐ１接合劑 TW201319068A (zh)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201161515404P 2011-08-05 2011-08-05

Publications (1)

Publication Number Publication Date
TW201319068A true TW201319068A (zh) 2013-05-16

Family

ID=46964007

Family Applications (1)

Application Number Title Priority Date Filing Date
TW101128158A TW201319068A (zh) 2011-08-05 2012-08-03 作為ｘｉａ因子抑制劑之環狀ｐ１接合劑

Country Status (8)

Country Link
US (2) US8901115B2 (OSRAM)
EP (2) EP3070087B1 (OSRAM)
JP (1) JP6113727B2 (OSRAM)
CN (2) CN103702999B (OSRAM)
AR (1) AR088423A1 (OSRAM)
ES (2) ES2563445T3 (OSRAM)
TW (1) TW201319068A (OSRAM)
WO (1) WO2013022814A1 (OSRAM)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
PH12014500625B1 (en) 2011-10-14 2018-12-12 Bristol Myers Squibb Co Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
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
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
HUE032622T2 (en) 2012-08-03 2017-10-30 Bristol Myers Squibb Co Dihydropyridone p1 as factor xia inhibitors
HRP20161378T1 (hr) * 2012-08-03 2016-12-02 Bristol-Myers Squibb Company Dihidropiridon kao faktor xia inhibitora
MX351848B (es) 2012-10-12 2017-10-31 Bristol Myers Squibb Co Formas cristalinas de inhibidor del factor xia.
WO2014059202A1 (en) 2012-10-12 2014-04-17 Bristol-Myers Squibb Company Guanidine substituted tetrahydroisoquinoline compounds 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
WO2014160668A1 (en) 2013-03-25 2014-10-02 Bristol-Myers Squibb Company Tetrahydroisoquinolines containing substituted azoles 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 (OSRAM) * 2014-01-31 2018-03-10
EP3104701B1 (en) * 2014-02-11 2019-01-30 Merck Sharp & Dohme Corp. Factor xia inhibitors
US9676723B2 (en) 2014-02-11 2017-06-13 Merck Sharp & Dohme Corp Factor XIa inhibitors
WO2015123093A1 (en) 2014-02-11 2015-08-20 Merck Sharp & Dohme Corp. Factor xia inhibitors
US10093683B2 (en) 2014-04-22 2018-10-09 Merck Sharp & Dohme Corp. Factor XIa inhibitors
US9868727B2 (en) 2014-07-28 2018-01-16 Merck Sharp & Dohme Corp. Factor XIa inhibitors
WO2016036893A1 (en) 2014-09-04 2016-03-10 Bristol-Myers Squibb Company Diamide macrocycles that are fxia inhibitors
NO2721243T3 (OSRAM) 2014-10-01 2018-10-20
US9453018B2 (en) 2014-10-01 2016-09-27 Bristol-Myers Squibb Company Pyrimidinones as factor XIa inhibitors
DK3231803T3 (da) * 2014-12-10 2020-08-24 Ono Pharmaceutical Co Dihydroindolizinonderivat
US10160750B2 (en) 2015-06-19 2018-12-25 Bristol-Myers Squibb Company Diamide macrocycles as factor XIa inhibitors
KR102729666B1 (ko) * 2015-07-29 2024-11-12 브리스톨-마이어스 스큅 컴퍼니 비-방향족 P2' 기를 갖는 인자 XIa 신규 마크로사이클
CN107849026B (zh) 2015-07-29 2021-01-01 百时美施贵宝公司 携带烷基或环烷基p2′部分的因子xia大环抑制剂
US10214512B2 (en) * 2015-10-29 2019-02-26 Merck Sharp & Dohme Corp. Factor XIA inhibitors
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
KR20180117156A (ko) 2016-03-02 2018-10-26 브리스톨-마이어스 스큅 컴퍼니 인자 XIa 억제 활성을 갖는 디아미드 마크로사이클
WO2018039094A1 (en) 2016-08-22 2018-03-01 Merck Sharp & Dohme Corp. Pyridine-1-oxide derivatives and their use as factor xia inhibitors
EP3301094A1 (en) * 2016-09-30 2018-04-04 Mutabilis Heterocyclic compounds and their use in preventing or treating bacterial infections
CN110062757B (zh) * 2017-01-18 2022-03-04 广东东阳光药业有限公司 凝血因子XIa抑制剂及其用途
WO2019011166A1 (zh) * 2017-07-14 2019-01-17 四川科伦博泰生物医药股份有限公司 大环酰胺化合物及其药物组合物和用途
ES2942214T3 (es) 2018-04-17 2023-05-30 Univ Michigan Regents Inhibidores de la función plaquetaria y procedimientos de utilización de los mismos
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
CN115490708B (zh) * 2021-06-18 2025-01-24 苏州亚盛药业有限公司 磺酰胺类大环衍生物及其制备方法和用途
CN119894901A (zh) * 2023-06-30 2025-04-25 深圳信立泰药业股份有限公司 一种多取代的大环化合物及其制备方法与应用

Family Cites Families (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0028489B1 (en) 1979-11-05 1983-10-05 Beecham Group Plc Enzyme derivatives, and their preparation
JPH0987280A (ja) * 1995-09-28 1997-03-31 Yamanouchi Pharmaceut Co Ltd オキソピペラジン誘導体又はその塩
PE121699A1 (es) 1997-02-18 1999-12-08 Boehringer Ingelheim Pharma Heterociclos biciclicos disustituidos como inhibidores de la trombina
ZA985247B (en) 1997-06-19 1999-12-17 Du Pont Merck Pharma Guanidine mimics as factor Xa inhibitors.
WO2000077027A2 (en) 1999-06-14 2000-12-21 Tularik Limited Serine protease inhibitors
DE19962924A1 (de) 1999-12-24 2001-07-05 Bayer Ag Substituierte Oxazolidinone und ihre Verwendung
AR035216A1 (es) 2000-12-01 2004-05-05 Astrazeneca Ab Derivados de acido mandelico ,derivados farmaceuticamente aceptables, uso de estos derivados para la fabricacion de medicamentos, metodos de tratamiento ,procesos para la preparacion de estos derivados, y compuestos intermediarios
WO2003011222A2 (en) * 2001-07-27 2003-02-13 Merck & Co., Inc. Thrombin inhibitors
AU2002341693B2 (en) 2001-09-21 2008-05-29 Bristol-Myers Squibb Holdings Ireland Unlimited Company Lactam-containing compounds and derivatives thereof as factor Xa inhibitors
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
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
EA014245B1 (ru) 2005-12-14 2010-10-29 Бристол-Маерс Сквибб Компани Аналоги арилпропионамида, арилакриламида, арилпропинамида или арилметилмочевины в качестве ингибиторов фактора xia
WO2007070816A2 (en) 2005-12-14 2007-06-21 Bristol-Myers Squibb Company Thiophene derivatives as factor xia inhibitors
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
CN101389613B (zh) * 2005-12-23 2011-10-12 布里斯托尔-迈尔斯.斯奎布公司 用作抗凝血药的大环凝血因子viia抑制剂
AR058380A1 (es) * 2005-12-23 2008-01-30 Bristol Myers Squibb Co Inhibidores del factor viia macrociclicos utiles como anticoagulantes
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
EP2070899A1 (en) 2007-12-14 2009-06-17 F. Hoffmann-La Roche Ag Deprotection of N-BOC compounds
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
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
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
PH12014500625B1 (en) 2011-10-14 2018-12-12 Bristol Myers Squibb Co Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
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
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
HUE032622T2 (en) 2012-08-03 2017-10-30 Bristol Myers Squibb Co Dihydropyridone p1 as factor xia inhibitors
HRP20161378T1 (hr) 2012-08-03 2016-12-02 Bristol-Myers Squibb Company Dihidropiridon kao faktor xia inhibitora
EP2906541B1 (en) 2012-10-12 2017-11-22 Bristol-Myers Squibb Company Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors
MX351848B (es) 2012-10-12 2017-10-31 Bristol Myers Squibb Co Formas cristalinas de inhibidor del factor xia.
WO2014059202A1 (en) 2012-10-12 2014-04-17 Bristol-Myers Squibb Company Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors

Also Published As

Publication number Publication date
US20150057262A1 (en) 2015-02-26
AR088423A1 (es) 2014-06-11
CN105294701B (zh) 2017-10-24
US8901115B2 (en) 2014-12-02
EP3070087B1 (en) 2019-04-10
EP2739625A1 (en) 2014-06-11
ES2563445T3 (es) 2016-03-15
JP6113727B2 (ja) 2017-04-12
WO2013022814A1 (en) 2013-02-14
CN103702999B (zh) 2015-11-25
US20140163002A1 (en) 2014-06-12
EP3070087A1 (en) 2016-09-21
CN105294701A (zh) 2016-02-03
US9108981B2 (en) 2015-08-18
EP2739625B1 (en) 2016-01-20
JP2014521700A (ja) 2014-08-28
CN103702999A (zh) 2014-04-02
ES2733096T3 (es) 2019-11-27

Similar Documents

Publication Publication Date Title
TW201319068A (zh) 作為ｘｉａ因子抑制劑之環狀ｐ１接合劑
TWI520965B (zh) 作為因子ｘｉａ抑制劑之巨環類
US10273236B2 (en) Macrocyclic factor XIa inhibitors bearing heterocyclic groups
EP2882734B1 (en) Dihydropyridone as factor xia inhibitors
KR102269999B1 (ko) 인자 XIa 억제제로서의 피리미디논
TW201311689A (zh) 作為因子ｘｉａ抑制劑之新穎巨環化合物
US20170096429A1 (en) Macrocycles with aromatic p2' groups as factor xia inhibitors
KR102086934B1 (ko) 알킬 또는 시클로알킬 P2' 모이어티를 갖는 인자 XIa 마크로시클릭 억제제
KR102729666B1 (ko) 비-방향족 P2' 기를 갖는 인자 XIa 신규 마크로사이클
HK40053570A (en) Pyrimidinones as factor xia inhibitors
HK40053570B (en) Pyrimidinones as factor xia inhibitors
HK1227032B (en) Pyrimidinones as factor xia inhibitors
HK1227032A1 (en) Pyrimidinones as factor xia inhibitors