CN103702999B - 作为因子xia抑制剂的环状p1连接体 - Google Patents

作为因子xia抑制剂的环状p1连接体 Download PDF

Info

Publication number
CN103702999B
CN103702999B CN201280037801.4A CN201280037801A CN103702999B CN 103702999 B CN103702999 B CN 103702999B CN 201280037801 A CN201280037801 A CN 201280037801A CN 103702999 B CN103702999 B CN 103702999B
Authority
CN
China
Prior art keywords
alkyl
mmol
compounds
compound
chloro
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.)
Active
Application number
CN201280037801.4A
Other languages
English (en)
Chinese (zh)
Other versions
CN103702999A (zh
Inventor
P.Y.S.林
C.G.克拉克
J.R.科尔特
W.R.尤因
P.J.吉利根
Y.雍
W.杨
L.M.史密斯二世
Y.王
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bristol Myers Squibb Co
Original Assignee
Bristol Myers Squibb Co
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 Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Priority to CN201510648908.8A priority Critical patent/CN105294701B/zh
Publication of CN103702999A publication Critical patent/CN103702999A/zh
Application granted granted Critical
Publication of CN103702999B publication Critical patent/CN103702999B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

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)
CN201280037801.4A 2011-08-05 2012-08-06 作为因子xia抑制剂的环状p1连接体 Active CN103702999B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510648908.8A CN105294701B (zh) 2011-08-05 2012-08-06 作为因子xia抑制剂的环状p1连接体

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201161515404P 2011-08-05 2011-08-05
US61/515,404 2011-08-05
US61/515404 2011-08-05
PCT/US2012/049698 WO2013022814A1 (en) 2011-08-05 2012-08-06 Cyclic p1 linkers as factor xia inhibitors

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CN201510648908.8A Division CN105294701B (zh) 2011-08-05 2012-08-06 作为因子xia抑制剂的环状p1连接体

Publications (2)

Publication Number Publication Date
CN103702999A CN103702999A (zh) 2014-04-02
CN103702999B true CN103702999B (zh) 2015-11-25

Family

ID=46964007

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201280037801.4A Active CN103702999B (zh) 2011-08-05 2012-08-06 作为因子xia抑制剂的环状p1连接体
CN201510648908.8A Active CN105294701B (zh) 2011-08-05 2012-08-06 作为因子xia抑制剂的环状p1连接体

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN201510648908.8A Active CN105294701B (zh) 2011-08-05 2012-08-06 作为因子xia抑制剂的环状p1连接体

Country Status (8)

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

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ602266A (en) 2010-02-11 2014-05-30 Bristol Myers Squibb Co 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
WO2013055984A1 (en) 2011-10-14 2013-04-18 Bristol-Myers Squibb Company Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
EP2766347B1 (en) 2011-10-14 2016-05-04 Bristol-Myers Squibb Company Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
JP6033319B2 (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
AU2013296259A1 (en) * 2012-08-03 2015-03-19 Bristol-Myers Squibb Company Dihydropyridone P1 as factor XIa inhibitors
US9376444B2 (en) * 2012-08-03 2016-06-28 Bristol-Myers Squibb Company Dihydropyridone P1 as factor XIa inhibitors
US9403774B2 (en) 2012-10-12 2016-08-02 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.
EP2906552B1 (en) 2012-10-12 2017-11-22 Bristol-Myers Squibb Company Guanidine 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 (https=) * 2014-01-31 2018-03-10
US9663527B2 (en) 2014-02-11 2017-05-30 Merck Sharp & Dohme Corp. Factor XIa inhibitors
WO2015123093A1 (en) 2014-02-11 2015-08-20 Merck Sharp & Dohme Corp. Factor xia inhibitors
WO2015123091A1 (en) 2014-02-11 2015-08-20 Merck Sharp & Dohme Corp. Factor xia inhibitors
EP3134408B1 (en) 2014-04-22 2020-08-12 Merck Sharp & Dohme Corp. FACTOR XIa INHIBITORS
WO2016015593A1 (en) 2014-07-28 2016-02-04 Merck Sharp & Dohme Corp. FACTOR XIa INHIBITORS
ES2714283T3 (es) 2014-09-04 2019-05-28 Bristol Myers Squibb Co Macrociclos de diamida que son inhibidores de FXIa
NO2721243T3 (https=) 2014-10-01 2018-10-20
US9453018B2 (en) 2014-10-01 2016-09-27 Bristol-Myers Squibb Company Pyrimidinones as factor XIa inhibitors
BR112017012146B1 (pt) * 2014-12-10 2023-11-21 Ono Pharmaceutical Co., Ltd Composto derivado de di-hidroindolizinona, seu uso, composição farmacêutica e inibidor de fxia
ES2762987T3 (es) * 2015-06-19 2020-05-26 Bristol Myers Squibb Co Macrociclos de diamida como inhibidores del factor XIA
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
CN114874222B (zh) 2015-07-29 2025-06-06 百时美施贵宝公司 携带非芳族p2,基团的因子xia新大环
EP3368036B1 (en) 2015-10-29 2022-07-20 Merck Sharp & Dohme LLC Macrocyclic pyridine-n-oxide derivatives as 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
HUE062236T2 (hu) * 2018-04-17 2023-10-28 Univ Michigan Regents Vérlemezke funkció inhibitorok és eljárás azok alkalmazására
WO2020211781A1 (zh) 2019-04-16 2020-10-22 南京明德新药研发有限公司 作为XIa因子抑制剂的大环衍生物
CN114008047B (zh) 2019-07-23 2023-03-21 南京明德新药研发有限公司 作为XIa因子抑制剂的大环衍生物
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
KR20260032556A (ko) * 2023-06-30 2026-03-09 심천 사루브리스 퍼머수티칼스 컴퍼니 리미티드 다치환된 거대환식 화합물 및 이의 제조 방법과 용도

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003011222A2 (en) * 2001-07-27 2003-02-13 Merck & Co., Inc. Thrombin inhibitors
CN101389613A (zh) * 2005-12-23 2009-03-18 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
CN102026996A (zh) * 2008-03-13 2011-04-20 百时美施贵宝公司 作为凝血因子xia抑制剂的哒嗪衍生物

Family Cites Families (34)

* 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
CN104744461A (zh) 2001-09-21 2015-07-01 百时美施贵宝公司 含有内酰胺的化合物及其衍生物作为Xa因子的抑制剂
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
US20060183771A1 (en) 2005-02-17 2006-08-17 Seiffert Dietmar A Novel combination of selective factor VIIa and/or factor XIa inhibitors and selective plasma kallikrein inhibitors
NZ568595A (en) 2005-12-14 2010-04-30 Bristol Myers Squibb Co Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor Xla inhibitors
WO2007070816A2 (en) 2005-12-14 2007-06-21 Bristol-Myers Squibb Company Thiophene derivatives as factor xia inhibitors
EP1966141A1 (en) 2005-12-14 2008-09-10 Brystol-Myers Squibb Company Six-membered heterocycles useful as serine protease inhibitors
PE20071132A1 (es) * 2005-12-23 2007-12-14 Bristol Myers Squibb Co Compuestos macrociclicos como inhibidores del factor viia
EP2102189B1 (en) 2006-12-15 2015-07-29 Bristol-Myers Squibb Company Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor xia inhibitors
CN101784516B (zh) 2007-06-13 2014-07-02 百时美施贵宝公司 作为凝血因子抑制剂的二肽类似物
EP2070899A1 (en) 2007-12-14 2009-06-17 F. Hoffmann-La Roche Ag Deprotection of N-BOC compounds
NZ602266A (en) * 2010-02-11 2014-05-30 Bristol Myers Squibb Co 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
EP2766347B1 (en) 2011-10-14 2016-05-04 Bristol-Myers Squibb Company Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
JP6033319B2 (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
WO2013055984A1 (en) 2011-10-14 2013-04-18 Bristol-Myers Squibb Company Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
US9376444B2 (en) 2012-08-03 2016-06-28 Bristol-Myers Squibb Company Dihydropyridone P1 as factor XIa inhibitors
AU2013296259A1 (en) 2012-08-03 2015-03-19 Bristol-Myers Squibb Company Dihydropyridone P1 as factor XIa inhibitors
US9403774B2 (en) 2012-10-12 2016-08-02 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.
EP2906552B1 (en) 2012-10-12 2017-11-22 Bristol-Myers Squibb Company Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003011222A2 (en) * 2001-07-27 2003-02-13 Merck & Co., Inc. Thrombin inhibitors
CN101389613A (zh) * 2005-12-23 2009-03-18 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
CN102026996A (zh) * 2008-03-13 2011-04-20 百时美施贵宝公司 作为凝血因子xia抑制剂的哒嗪衍生物

Also Published As

Publication number Publication date
EP3070087B1 (en) 2019-04-10
CN105294701A (zh) 2016-02-03
US8901115B2 (en) 2014-12-02
US20150057262A1 (en) 2015-02-26
CN103702999A (zh) 2014-04-02
AR088423A1 (es) 2014-06-11
US9108981B2 (en) 2015-08-18
TW201319068A (zh) 2013-05-16
WO2013022814A1 (en) 2013-02-14
EP2739625B1 (en) 2016-01-20
JP2014521700A (ja) 2014-08-28
EP3070087A1 (en) 2016-09-21
CN105294701B (zh) 2017-10-24
EP2739625A1 (en) 2014-06-11
JP6113727B2 (ja) 2017-04-12
ES2563445T3 (es) 2016-03-15
ES2733096T3 (es) 2019-11-27
US20140163002A1 (en) 2014-06-12

Similar Documents

Publication Publication Date Title
CN103702999B (zh) 作为因子xia抑制剂的环状p1连接体
AU2021245098B2 (en) Pyrimidinones as factor XIa inhibitors
JP5841547B2 (ja) 第ｘｉａ因子阻害剤としてのマクロ環
US9376444B2 (en) Dihydropyridone P1 as factor XIa inhibitors
CN105228996B (zh) 作为因子XIa抑制剂的含取代唑类的四氢异喹啉
JP6082463B2 (ja) 第ｘｉａ因子阻害剤としてのジヒドロピリドンｐ１
CN102026996B (zh) 作为凝血因子xia抑制剂的哒嗪衍生物
CN108137549A (zh) 新颖的取代的甘氨酸衍生的fxia抑制剂
CN107074821A (zh) 作为fxia抑制剂的二胺大环化合物
CN114874222B (zh) 携带非芳族p2,基团的因子xia新大环
HK40053570A (en) Pyrimidinones as factor xia inhibitors
HK40053570B (en) Pyrimidinones as factor xia inhibitors
HK1227032A1 (en) Pyrimidinones as factor xia inhibitors
HK1227032B (en) Pyrimidinones as factor xia inhibitors

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant