CA2937738C - Macrocyclic factor xia inhibitors condensed with heterocycles - Google Patents

Macrocyclic factor xia inhibitors condensed with heterocycles Download PDF

Info

Publication number
CA2937738C
CA2937738C CA2937738A CA2937738A CA2937738C CA 2937738 C CA2937738 C CA 2937738C CA 2937738 A CA2937738 A CA 2937738A CA 2937738 A CA2937738 A CA 2937738A CA 2937738 C CA2937738 C CA 2937738C
Authority
CA
Canada
Prior art keywords
independently
chloro
mmol
chf2
oxo
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
CA2937738A
Other languages
English (en)
French (fr)
Other versions
CA2937738A1 (en
Inventor
Andrew K. Dilger
James R. Corte
Indawati De Lucca
Tianan Fang
Wu Yang
Yufeng Wang
Kumar Balashanmuga PABBISETTY
William R. Ewing
Yeheng Zhu
Ruth R. Wexler
Donald J.P. Pinto
Michael J. Orwat
Leon M. Ii Smith
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
Publication of CA2937738A1 publication Critical patent/CA2937738A1/en
Application granted granted Critical
Publication of CA2937738C publication Critical patent/CA2937738C/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/18—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A61P9/06—Antiarrhythmics
    • 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
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (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)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
CA2937738A 2014-01-31 2015-01-30 Macrocyclic factor xia inhibitors condensed with heterocycles Active CA2937738C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201461933948P 2014-01-31 2014-01-31
US61/933,948 2014-01-31
PCT/US2015/013647 WO2015116882A1 (en) 2014-01-31 2015-01-30 Macrocyclic factor xia inhibitors condensed with heterocycles

Publications (2)

Publication Number Publication Date
CA2937738A1 CA2937738A1 (en) 2015-08-06
CA2937738C true CA2937738C (en) 2023-01-17

Family

ID=52484569

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2937738A Active CA2937738C (en) 2014-01-31 2015-01-30 Macrocyclic factor xia inhibitors condensed with heterocycles

Country Status (24)

Country Link
US (3) US20170057961A1 (enExample)
EP (1) EP3099688B1 (enExample)
JP (1) JP6419836B2 (enExample)
CN (1) CN106459051B (enExample)
AR (1) AR099228A1 (enExample)
BR (1) BR112016016741B1 (enExample)
CA (1) CA2937738C (enExample)
CY (1) CY1120534T1 (enExample)
DK (1) DK3099688T3 (enExample)
EA (1) EA032650B1 (enExample)
ES (1) ES2655540T3 (enExample)
HR (1) HRP20172002T1 (enExample)
HU (1) HUE038060T2 (enExample)
LT (1) LT3099688T (enExample)
MX (1) MX2016009385A (enExample)
NO (1) NO2760821T3 (enExample)
PL (1) PL3099688T3 (enExample)
PT (1) PT3099688T (enExample)
RS (1) RS56785B1 (enExample)
SI (1) SI3099688T1 (enExample)
SM (1) SMT201800024T1 (enExample)
TW (1) TWI703144B (enExample)
UY (1) UY35972A (enExample)
WO (1) WO2015116882A1 (enExample)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103974938B (zh) 2011-10-14 2016-11-09 百时美施贵宝公司 作为因子xia抑制剂的经取代的四氢异喹啉化合物
ES2712699T3 (es) 2013-03-25 2019-05-14 Bristol Myers Squibb Co Tetrahidroisoquinolinas que contienen azoles sustituidos como inhibidores del factor XIa
NO2760821T3 (enExample) 2014-01-31 2018-03-10
TWI688564B (zh) 2014-01-31 2020-03-21 美商必治妥美雅史谷比公司 作為凝血因子ｘｉａ抑制劑之具有雜環p2'基團之巨環化合物
WO2016036893A1 (en) 2014-09-04 2016-03-10 Bristol-Myers Squibb Company Diamide macrocycles that are fxia inhibitors
US9453018B2 (en) 2014-10-01 2016-09-27 Bristol-Myers Squibb Company Pyrimidinones as factor XIa inhibitors
NO2721243T3 (enExample) * 2014-10-01 2018-10-20
ES2762987T3 (es) 2015-06-19 2020-05-26 Bristol Myers Squibb Co Macrociclos de diamida como inhibidores del factor XIA
ES2871111T3 (es) 2015-07-29 2021-10-28 Bristol Myers Squibb Co Inhibidores macrocíclicos del factor XIa que contienen un grupo P2' no aromático
KR102086934B1 (ko) * 2015-07-29 2020-03-09 브리스톨-마이어스 스큅 컴퍼니 알킬 또는 시클로알킬 P2' 모이어티를 갖는 인자 XIa 마크로시클릭 억제제
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
AU2016344476B2 (en) * 2015-10-29 2020-08-13 Merck Sharp & Dohme Llc Factor XIa inhibitors
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
CN110248938A (zh) 2016-11-23 2019-09-17 拜耳作物科学股份公司 用作农药的2-[3-(烷基磺酰基)-2h-吲唑-2-基]-3h-咪唑并[4,5-b]吡啶衍生物和类似化合物
AU2018207776B2 (en) 2017-01-10 2021-06-17 Bayer Aktiengesellschaft Heterocyclene derivatives as pest control agents
MX2019008230A (es) 2017-01-10 2019-10-24 Bayer Ag Derivados heterociclicos como agentes de control de plagas.
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
CN110922412A (zh) * 2018-09-20 2020-03-27 复旦大学 具有抗精神病作用药物化合物的不对称合成方法
EP3957638B1 (en) * 2019-04-16 2025-01-08 China Resources Biopharmaceutical Company Limited Macrocyclic derivatives acting as xia factor inhibitor
WO2021007354A1 (en) * 2019-07-08 2021-01-14 Gary Sharp Innovations, Llc Compact polarization-based collimators with high contrast
JP7286001B2 (ja) * 2019-07-23 2023-06-02 メッドシャイン ディスカバリー インコーポレイテッド 第ＸＩａ因子阻害剤としての大環状誘導体
TW202229280A (zh) * 2020-10-12 2022-08-01 美商必治妥美雅史谷比公司 （６ｒ，１０ｓ）－１０－｛４－［５－氯－２－（４－氯－１ｈ－１，２，３－三唑－１－基）苯基］－６－側氧基－１（６ｈ）－嘧啶基｝－１－（二氟甲基）－６－甲基－１，４，７，８，９，１０－六氫－１１，１５－（亞甲橋基）吡唑并［４，３－ｂ］［１，７］二氮雜環十四炔－５（６ｈ）－酮之製備方法
TWI877478B (zh) * 2021-04-21 2025-03-21 大陸商上海美悦生物科技發展有限公司 FXIa抑制劑及其藥物組合物、製備方法和用途
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 (107)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1525186A (fr) 1967-03-29 1968-05-17 Roussel Uclaf Nouvelles pénicillines et procédé de préparation
DE3065190D1 (en) 1979-11-05 1983-11-10 Beecham Group Plc Enzyme derivatives, and their preparation
DE4034829A1 (de) 1990-11-02 1992-05-07 Merck Patent Gmbh Cyclopeptide
JP3190431B2 (ja) 1991-07-01 2001-07-23 三菱化学株式会社 ケトン誘導体
GB9206757D0 (en) 1992-03-27 1992-05-13 Ferring Bv Novel peptide receptor ligands
US5624936A (en) 1995-03-29 1997-04-29 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
WO1996034010A2 (en) 1995-03-29 1996-10-31 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
EP0891352A4 (en) 1996-04-03 2001-08-16 Merck & Co Inc INHIBITORS OF FARNESYL PROTEIN TRANSFERASE
US5869682A (en) 1996-04-03 1999-02-09 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
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.
TW557297B (en) 1997-09-26 2003-10-11 Abbott Lab Rapamycin analogs having immunomodulatory activity, and pharmaceutical compositions containing same
KR100898094B1 (ko) 1998-03-19 2009-05-18 버텍스 파마슈티칼스 인코포레이티드 카스파제의 억제제
EE200000706A (et) 1998-05-26 2002-06-17 Warner-Lambert Company Bitsüklilised pürimidiinid ja bitsüklilised 3,4-dihüdropürimidiinid kui rakkude proliferatsiooni inhibiitorid
US6307049B1 (en) 1998-09-30 2001-10-23 The Procter & Gamble Co. Heterocyclic 2-substituted ketoamides
AU3043100A (en) 1999-01-02 2000-07-24 Aventis Pharma Deutschland Gmbh Novel malonic acid derivatives, processes for their preparation, their use and pharmaceutical compositions containing them (inhibition of factor xa activity)
EP1016663A1 (en) 1999-01-02 2000-07-05 Aventis Pharma Deutschland GmbH Novel malonic acid derivatives, processes for their preparation, their use and pharmaceutical compositions containing them (inhibition of factor Xa activity)
DE50008510D1 (de) 1999-04-09 2004-12-09 Abbott Gmbh & Co Kg Niedermolekulare inhibitoren von komplementproteasen
CA2383008A1 (en) 1999-06-14 2000-12-21 Amanda Jane Lyons Compounds
DE19962924A1 (de) 1999-12-24 2001-07-05 Bayer Ag Substituierte Oxazolidinone und ihre Verwendung
EP1125925A1 (en) 2000-02-15 2001-08-22 Applied Research Systems ARS Holding N.V. Amine derivatives for the treatment of apoptosis
CA2408486A1 (en) 2000-05-11 2001-11-15 Bristol-Myers Squibb Company Tetrahydroisoquinoline analogs useful as growth hormone secretagogues
SV2003000617A (es) 2000-08-31 2003-01-13 Lilly Co Eli Inhibidores de la proteasa peptidomimetica ref. x-14912m
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
AU2002322802A1 (en) 2001-07-27 2003-02-17 Merck And Co., Inc. Thrombin inhibitors
US6951840B2 (en) 2001-08-31 2005-10-04 Eli Lilly And Company Lipoglycopeptide antibiotics
CN110894196A (zh) 2001-09-21 2020-03-20 百时美-施贵宝控股爱尔兰无限公司 含有内酰胺的化合物及其衍生物作为Xa因子的抑制剂
WO2003041641A2 (en) 2001-11-09 2003-05-22 Bristol-Myers Squibb Company Tetrahydroisoquinoline analogs as modulators of chemokine receptor activity
WO2003106438A1 (en) 2002-06-18 2003-12-24 The Scripps Research Institute Synthesis of diazonamide "a" core
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
CA2531796A1 (en) 2003-08-08 2005-02-17 Transtech Pharma, Inc. Aryl and heteroaryl compounds, compositions, and methods of use
US7417063B2 (en) 2004-04-13 2008-08-26 Bristol-Myers Squibb Company Bicyclic 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
US7429604B2 (en) 2004-06-15 2008-09-30 Bristol Myers Squibb Company Six-membered heterocycles useful as serine protease inhibitors
EP2457895A1 (en) 2004-07-12 2012-05-30 Idun Pharmaceuticals, Inc. Tetrapeptide analogs
CN101137412B (zh) 2005-01-13 2012-11-07 布里斯托尔-迈尔斯·斯奎布公司 用作凝血因子XIa抑制剂的取代的二芳基化合物
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
WO2007047608A2 (en) 2005-10-14 2007-04-26 Epix Pharmaceuticals, Inc. Fibrin targeted therapeutics
AU2006311101A1 (en) 2005-11-11 2007-05-18 F. Hoffmann-La Roche Ag Carbocyclic fused cyclic amines as inhibitors of the coagulation factor Xa
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
US7626039B2 (en) 2005-12-14 2009-12-01 Bristol-Myers Squibb Company Arylpropionamide, arylacrylamide, ayrlpropynamide, or arylmethylurea analogs as factor XIa inhibitors
WO2007070816A2 (en) 2005-12-14 2007-06-21 Bristol-Myers Squibb Company Thiophene derivatives as factor xia inhibitors
AR058380A1 (es) 2005-12-23 2008-01-30 Bristol Myers Squibb Co Inhibidores del factor viia macrociclicos utiles como anticoagulantes
WO2008076805A2 (en) 2006-12-15 2008-06-26 Bristol-Myers Squibb Company Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor xia inhibitors
PE20081775A1 (es) 2006-12-20 2008-12-18 Bristol Myers Squibb Co Compuestos macrociclicos como inhibidores del factor viia
AU2008266228A1 (en) 2007-06-13 2008-12-24 Bristol-Myers Squibb Company Dipeptide analogs as coagulation factor inhibitors
WO2009114677A1 (en) 2008-03-13 2009-09-17 Bristol-Myers Squibb Company Pyridazine derivatives as factor xia inhibitors
US8624040B2 (en) 2009-06-22 2014-01-07 Millennium Pharmaceuticals, Inc. Substituted hydroxamic acids and uses thereof
US8513433B2 (en) 2009-07-02 2013-08-20 Angion Biomedica Corp. Small molecule inhibitors of PARP activity
EP2462123B1 (en) 2009-08-04 2013-10-02 Merck Sharp & Dohme Corp. 4,5,6-trisubstituted pyrimidine derivatives as factor ixa inhibitors
EP2534152B1 (en) 2010-02-11 2018-05-02 Bristol-Myers Squibb Company Macrocycles as factor xia inhibitors
EP2729150B1 (en) 2011-07-08 2016-09-14 Merck Sharp & Dohme Corp. Factor ixa 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
ES2699226T3 (es) 2011-10-14 2019-02-08 Bristol Myers Squibb Co Compuestos de tetrahidroisoquinolina sustituidos como inhibidores del factor XIa
IN2014CN02805A (enExample) 2011-10-14 2015-07-03 Bristol Myers Squibb Co
CN103974938B (zh) 2011-10-14 2016-11-09 百时美施贵宝公司 作为因子xia抑制剂的经取代的四氢异喹啉化合物
CN104136431B (zh) 2011-12-21 2017-03-15 小野药品工业株式会社 作为凝血因子XIa抑制剂的吡啶酮和嘧啶酮衍生物
GB2497806A (en) 2011-12-21 2013-06-26 Ono Pharmaceutical Co Pyridinone and pyrimidinone derivatives as factor XIa inhibitors
EP2807156A1 (en) 2012-01-27 2014-12-03 Novartis AG Aminopyridine derivatives as plasma kallikrein inhibitors
WO2013111108A1 (en) 2012-01-27 2013-08-01 Novartis Ag 5-membered heteroarylcarboxamide derivatives as plasma kallikrein inhibitors
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
EP2847228B1 (en) 2012-05-10 2018-07-25 Bayer Pharma Aktiengesellschaft Antibodies capable of binding to the coagulation factor xi and/or its activated form factor xia and uses thereof
GB201209138D0 (en) 2012-05-24 2012-07-04 Ono Pharmaceutical Co Compounds
AU2013291098A1 (en) 2012-07-19 2015-02-05 Sumitomo Dainippon Pharma Co., Ltd. 1-(cycloalkyl-carbonyl)proline derivative
SG11201500270RA (en) * 2012-08-03 2015-03-30 Bristol Myers Squibb Co Dihydropyridone p1 as factor xia inhibitors
US9409908B2 (en) * 2012-08-03 2016-08-09 Bristol-Myers Squibb Company Dihydropyridone p1 as factor XIa inhibitors
JP6154473B2 (ja) 2012-10-12 2017-06-28 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因子阻害剤の結晶形
US9315519B2 (en) 2012-10-12 2016-04-19 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
WO2014120346A1 (en) 2012-12-19 2014-08-07 Merck Sharp & Dohme Corp. Factor ixa inhibitors
GB201300304D0 (en) 2013-01-08 2013-02-20 Kalvista Pharmaceuticals Ltd Benzylamine derivatives
GB2510407A (en) 2013-02-04 2014-08-06 Kalvista Pharmaceuticals Ltd Aqueous suspensions of kallikrein inhibitors for parenteral administration
ES2712699T3 (es) 2013-03-25 2019-05-14 Bristol Myers Squibb Co Tetrahidroisoquinolinas que contienen azoles sustituidos como inhibidores del factor XIa
TWI633089B (zh) 2013-03-28 2018-08-21 拜耳製藥股份有限公司 經取代的酮基吡啶衍生物
US9475809B2 (en) 2013-07-23 2016-10-25 Bayer Pharma Aktiengesellschaft Substituted oxopyridine derivatives and use thereof as factor xia/plasma
EP3049404A1 (de) 2013-09-26 2016-08-03 Bayer Pharma Aktiengesellschaft Substituierte phenylalanin-derivate
EP3049403A1 (de) 2013-09-26 2016-08-03 Bayer Pharma Aktiengesellschaft Substituierte phenylalanin-derivate
WO2015044173A1 (de) 2013-09-26 2015-04-02 Bayer Pharma Aktiengesellschaft Substituierte phenylalanin-derivate als faktor xia modulatoren
EP3049394A1 (de) 2013-09-26 2016-08-03 Bayer Pharma Aktiengesellschaft Substituierte phenylalanin-derivate als faktor xia modulatoren
EP3049408A1 (de) 2013-09-26 2016-08-03 Bayer Pharma Aktiengesellschaft Substituierte phenylalanin-derivate
TW201605809A (zh) 2013-09-26 2016-02-16 拜耳製藥股份有限公司 經取代苯丙胺酸衍生物（一）
US20160237044A1 (en) 2013-09-26 2016-08-18 Bayer Pharma Aktiengesellschaft Substituted phenylalanine derivatives
MA38925B1 (fr) 2013-09-26 2018-09-28 Bayer Pharma AG Dérivés de phénylalanine substitués
EP3049435A4 (en) 2013-09-27 2017-03-29 Merck Sharp & Dohme Corp. Factor xia inhibitors
EP3054944B1 (en) 2013-10-07 2019-12-04 Merck Sharp & Dohme Corp. Factor xia inhibitors
JP6337750B2 (ja) 2013-11-22 2018-06-06 小野薬品工業株式会社 化合物
CA2939326A1 (en) 2014-01-14 2015-07-23 Sumitomo Dainippon Pharma Co., Ltd. Condensed 5-oxazolidinone derivative
NO2760821T3 (enExample) 2014-01-31 2018-03-10
TWI688564B (zh) 2014-01-31 2020-03-21 美商必治妥美雅史谷比公司 作為凝血因子ｘｉａ抑制劑之具有雜環p2'基團之巨環化合物
KR101927114B1 (ko) 2014-02-07 2018-12-10 엑시테라 파마슈티컬스 인코퍼레이티드 치료 화합물 및 조성물
US9676723B2 (en) 2014-02-11 2017-06-13 Merck Sharp & Dohme Corp Factor XIa inhibitors
US9944643B2 (en) 2014-02-11 2018-04-17 Merck Sharp & Dohme Corp. Factor XIa inhibitors
EP3104701B1 (en) 2014-02-11 2019-01-30 Merck Sharp & Dohme Corp. Factor xia inhibitors
CN105829298B (zh) 2014-02-14 2019-02-01 四川海思科制药有限公司 一种吡啶酮或嘧啶酮衍生物、及其制备方法和应用
PL3828173T3 (pl) 2014-03-07 2022-12-19 Biocryst Pharmaceuticals, Inc. Podstawiane pirazole jako inhibitory ludzkiej kalikreiny osoczowej
US9969724B2 (en) 2014-04-16 2018-05-15 Merck Sharp & Dohme Corp. Factor IXa inhibitors
WO2015160634A1 (en) 2014-04-16 2015-10-22 Merck Sharp & Dohme Corp. Factor ixa inhibitors
KR20150136294A (ko) 2014-05-27 2015-12-07 주식회사 레고켐 바이오사이언스 인자 ＸＩａ 억제 활성을 가지는 신규한 화합물
KR20170005871A (ko) 2014-05-28 2017-01-16 머크 샤프 앤드 돔 코포레이션 인자 XIa 억제제
ES2712886T3 (es) 2014-09-24 2019-05-16 Bayer Pharma AG Derivados de piridobenzazepina y piridobenzazocina que inhiben el factor XIa
US9453018B2 (en) 2014-10-01 2016-09-27 Bristol-Myers Squibb Company Pyrimidinones as factor XIa inhibitors
NO2721243T3 (enExample) 2014-10-01 2018-10-20
EP3231803B1 (en) 2014-12-10 2020-07-01 ONO Pharmaceutical Co., Ltd. Dihydroindolizinone derivative
ES2762987T3 (es) 2015-06-19 2020-05-26 Bristol Myers Squibb Co Macrociclos de diamida como inhibidores del factor XIA

Also Published As

Publication number Publication date
WO2015116882A1 (en) 2015-08-06
HUE038060T2 (hu) 2018-09-28
BR112016016741B1 (pt) 2023-01-17
RS56785B1 (sr) 2018-04-30
SI3099688T1 (sl) 2017-12-29
DK3099688T3 (en) 2018-01-15
SMT201800024T1 (it) 2018-03-08
TW201615640A (zh) 2016-05-01
HRP20172002T1 (hr) 2018-02-09
NO2760821T3 (enExample) 2018-03-10
JP6419836B2 (ja) 2018-11-07
US20170057961A1 (en) 2017-03-02
ES2655540T3 (es) 2018-02-20
TWI703144B (zh) 2020-09-01
PL3099688T3 (pl) 2018-03-30
MX2016009385A (es) 2016-09-16
CN106459051B (zh) 2018-10-16
EP3099688B1 (en) 2017-10-18
AR099228A1 (es) 2016-07-06
US20180222907A1 (en) 2018-08-09
LT3099688T (lt) 2017-12-27
EA032650B1 (ru) 2019-06-28
CA2937738A1 (en) 2015-08-06
PT3099688T (pt) 2018-01-15
US20170342071A1 (en) 2017-11-30
EP3099688A1 (en) 2016-12-07
UY35972A (es) 2015-07-31
CY1120534T1 (el) 2019-07-10
EA201691561A1 (ru) 2017-01-30
US10273236B2 (en) 2019-04-30
JP2017504640A (ja) 2017-02-09
CN106459051A (zh) 2017-02-22
BR112016016741A2 (enExample) 2017-08-08

Similar Documents

Publication Publication Date Title
CA2937738C (en) Macrocyclic factor xia inhibitors condensed with heterocycles
CA2963395C (en) Pyrimidinones as factor xia inhibitors
CA2937739C (en) Macrocycles with heterocyclic p2' groups as factor xia inhibitors
CA2880866A1 (en) Dihydropyridone p1 as factor xia inhibitors
EP3328851B1 (en) Factor xia macrocyclic inhibitors bearing alkyl or cycloalkyl p2' moieties
EP3310777B1 (en) Diamide macrocycles as factor xia inhibitors
EP3328852B1 (en) Factor xia macrocyclic inhibitors bearing a non-aromatic p2' group
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
BR112017006702B1 (pt) Pirimidinonas inibidoras de fator xia, composição farmacêutica e seu uso

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20200117

EEER Examination request

Effective date: 20200117

EEER Examination request

Effective date: 20200117

EEER Examination request

Effective date: 20200117

EEER Examination request

Effective date: 20200117

EEER Examination request

Effective date: 20200117

EEER Examination request

Effective date: 20200117

MPN Maintenance fee for patent paid

Free format text: FEE DESCRIPTION TEXT: MF (PATENT, 10TH ANNIV.) - STANDARD

Year of fee payment: 10

U00 Fee paid

Free format text: ST27 STATUS EVENT CODE: A-4-4-U10-U00-U101 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE REQUEST RECEIVED

Effective date: 20241205

U11 Full renewal or maintenance fee paid

Free format text: ST27 STATUS EVENT CODE: A-4-4-U10-U11-U102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE FEE PAYMENT DETERMINED COMPLIANT

Effective date: 20241205