PH12016501249B1 - Macrocycles with hetrocyclic p2` groups as factor xia inhibitors - Google Patents

Macrocycles with hetrocyclic p2` groups as factor xia inhibitors

Info

Publication number
PH12016501249B1
PH12016501249B1 PH12016501249A PH12016501249A PH12016501249B1 PH 12016501249 B1 PH12016501249 B1 PH 12016501249B1 PH 12016501249 A PH12016501249 A PH 12016501249A PH 12016501249 A PH12016501249 A PH 12016501249A PH 12016501249 B1 PH12016501249 B1 PH 12016501249B1
Authority
PH
Philippines
Prior art keywords
factor xia
hetrocyclic
macrocycles
groups
xia inhibitors
Prior art date
Application number
PH12016501249A
Other languages
English (en)
Other versions
PH12016501249A1 (en
Inventor
James R Corte
Lucca Indawati De
Tianan Fang
Wu Yang
Yufeng Wang
Andrew K Dilger
Kumar Balashanmuga Pabbisetty
William R Ewing
Yeheng Zhu
Ruth R Wexler
Donald J P Pinto
Michael J Orwat
Leon M Ii Smith
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=52484570&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=PH12016501249(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co
Publication of PH12016501249A1 publication Critical patent/PH12016501249A1/en
Publication of PH12016501249B1 publication Critical patent/PH12016501249B1/en

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
    • C07D471/02—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
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4192—1,2,3-Triazoles
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • 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
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • 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
    • 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
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 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
    • C07D471/12—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
    • 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)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Epidemiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Vascular Medicine (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Compression Or Coding Systems Of Tv Signals (AREA)
PH12016501249A 2014-01-31 2016-06-24 Macrocycles with hetrocyclic p2` groups as factor xia inhibitors PH12016501249B1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201461933942P 2014-01-31 2014-01-31
US201462058293P 2014-10-01 2014-10-01
PCT/US2015/013654 WO2015116886A1 (en) 2014-01-31 2015-01-30 Macrocycles with hetrocyclic p2' groups as factor xia inhibitors

Publications (2)

Publication Number Publication Date
PH12016501249A1 PH12016501249A1 (en) 2016-08-15
PH12016501249B1 true PH12016501249B1 (en) 2022-01-21

Family

ID=52484570

Family Applications (2)

Application Number Title Priority Date Filing Date
PH12016501249A PH12016501249B1 (en) 2014-01-31 2016-06-24 Macrocycles with hetrocyclic p2` groups as factor xia inhibitors
PH12021550418A PH12021550418A1 (en) 2014-01-31 2021-02-26 Macrocycles with hetrocyclic p2` groups as factor xia inhibitors

Family Applications After (1)

Application Number Title Priority Date Filing Date
PH12021550418A PH12021550418A1 (en) 2014-01-31 2021-02-26 Macrocycles with hetrocyclic p2` groups as factor xia inhibitors

Country Status (32)

Country Link
US (2) US20170002006A1 (OSRAM)
EP (4) EP3099687B1 (OSRAM)
JP (6) JP6464176B2 (OSRAM)
KR (3) KR102631769B1 (OSRAM)
CN (4) CN110845498B (OSRAM)
AU (5) AU2015210904C1 (OSRAM)
BR (1) BR112016015717B1 (OSRAM)
CA (1) CA2937739C (OSRAM)
CL (1) CL2016001933A1 (OSRAM)
CY (1) CY1120702T1 (OSRAM)
DK (1) DK3099687T3 (OSRAM)
EA (1) EA030222B1 (OSRAM)
ES (3) ES2687498T3 (OSRAM)
HR (1) HRP20181339T1 (OSRAM)
HU (1) HUE040226T2 (OSRAM)
IL (5) IL298983B2 (OSRAM)
LT (1) LT3099687T (OSRAM)
MX (2) MX377545B (OSRAM)
MY (1) MY190429A (OSRAM)
NZ (2) NZ761182A (OSRAM)
PE (2) PE20161069A1 (OSRAM)
PH (2) PH12016501249B1 (OSRAM)
PL (1) PL3099687T3 (OSRAM)
PT (1) PT3099687T (OSRAM)
RS (1) RS57659B1 (OSRAM)
SG (2) SG11201606209PA (OSRAM)
SI (1) SI3099687T1 (OSRAM)
SM (1) SMT201800505T1 (OSRAM)
TW (4) TW201613922A (OSRAM)
UY (3) UY40230A (OSRAM)
WO (2) WO2015116886A1 (OSRAM)
ZA (1) ZA201606011B (OSRAM)

Families Citing this family (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201116559D0 (en) 2011-09-26 2011-11-09 Univ Leuven Kath Novel viral replication inhibitors
EP3309148A1 (en) 2011-10-14 2018-04-18 Bristol-Myers Squibb Company Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
US9738655B2 (en) 2013-03-25 2017-08-22 Bristol-Myers Squibb Company Tetrahydroisoquinolines containing substituted azoles as factor XIa inhibitors
NO2760821T3 (OSRAM) 2014-01-31 2018-03-10
UY40230A (es) * 2014-01-31 2023-08-15 Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware Macrociclos con grupos P2’ heterocíclicos como inhibidores del factor XIa y composiciones farmacéuticas que los comprenden
EP2913330A1 (en) 2014-02-27 2015-09-02 Laboratoire Biodim Condensed derivatives of imidazole useful as pharmaceuticals
ES2714283T3 (es) 2014-09-04 2019-05-28 Bristol Myers Squibb Co Macrociclos de diamida que son inhibidores de FXIa
NO2721243T3 (OSRAM) * 2014-10-01 2018-10-20
SG11201702628XA (en) 2014-10-01 2017-04-27 Merck Patent Gmbh Boronic acid derivatives
US9453018B2 (en) 2014-10-01 2016-09-27 Bristol-Myers Squibb Company Pyrimidinones as factor XIa inhibitors
JOP20160086B1 (ar) 2015-05-08 2021-08-17 2 Katholieke Univ Leuven Ku Leuven Research And Development مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك
EP3310777B1 (en) 2015-06-19 2019-10-09 Bristol-Myers Squibb Company Diamide macrocycles as factor xia inhibitors
JO3703B1 (ar) 2015-07-09 2021-01-31 Bayer Pharma AG مشتقات أوكسوبيريدين مستبدلة
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
US10676477B2 (en) 2015-07-29 2020-06-09 Bristol-Myers Squibb Company Factor XIa macrocycle inhibitors bearing a non-aromatic P2' group
JOP20160198B1 (ar) 2015-09-16 2022-03-14 Janssen Pharmaceuticals Inc مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك
JO3633B1 (ar) 2015-09-16 2020-08-27 Katholieke Univ Leuven Ku Leuven Research & Development مشتقات اندول مستبدلة احاديا او ثنائيا بصفتها مانعات للتكاثر الفيروسي لحمى الفنك
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
US10214512B2 (en) * 2015-10-29 2019-02-26 Merck Sharp & Dohme Corp. Factor XIA inhibitors
EP3423458A1 (en) 2016-03-02 2019-01-09 Bristol-Myers Squibb Company Diamide macrocycles having factor xia inhibiting activity
KR102359743B1 (ko) 2016-03-31 2022-02-07 얀센 파마슈티칼즈, 인코포레이티드 뎅기 바이러스 복제 억제제로서의 치환 인돌 유도체
KR102359735B1 (ko) 2016-03-31 2022-02-08 얀센 파마슈티칼즈, 인코포레이티드 뎅기 바이러스 복제 억제제로서의 치환 인돌린 유도체
SG11201808237UA (en) 2016-04-01 2018-10-30 Janssen Pharmaceuticals Inc Substituted indole compound derivatives as dengue viral replication inhibitors
JOP20170069B1 (ar) 2016-04-01 2021-08-17 1 Janssen Pharmaceuticals Inc مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك
AR109304A1 (es) 2016-08-10 2018-11-21 Sumitomo Chemical Co Compuesto de oxadiazol y su uso
EP3500556B1 (en) 2016-08-22 2023-08-02 Merck Sharp & Dohme LLC Pyridine-1-oxide derivatives and their use as factor xia inhibitors
WO2018133793A1 (zh) * 2017-01-18 2018-07-26 广东东阳光药业有限公司 凝血因子XIa抑制剂及其用途
JOP20180025B1 (ar) 2017-03-31 2021-08-17 Janssen Pharmaceuticals Inc مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك
JOP20180026A1 (ar) 2017-03-31 2019-01-30 Univ Leuven Kath مشتقات اندولين مستبدلة بصفتها مانعات للتكاثر الفيروسي لحمى الفنك
BR112019024311A2 (pt) 2017-05-22 2020-07-28 Janssen Pharmaceuticals, Inc. derivados de indolina substituídos como inibidores da replicação viral do dengue
US11407715B2 (en) 2017-05-22 2022-08-09 Janssen Pharmaceuticals, Inc. Substituted indoline derivatives as dengue viral replication inhibitors
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
CN119775276A (zh) 2019-04-11 2025-04-08 百时美施贵宝公司 制备化合物的新颖合成选项
KR20210151183A (ko) * 2019-04-11 2021-12-13 브리스톨-마이어스 스큅 컴퍼니 치료 혈장 농도를 달성하기 위한 무정형 고체 및 가용화된 제제의 증진된 성능
JP7270770B2 (ja) * 2019-04-16 2023-05-10 チャイナ・リソースズ・バイオファーマシューティカル・カンパニー・リミテッド ＸＩａ因子阻害剤としての大環状誘導体
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
TWI749881B (zh) * 2019-11-21 2021-12-11 大陸商深圳信立泰藥業股份有限公司 二氧代哌類衍生物、其製備方法及其在醫藥上的應用
US20230151010A1 (en) * 2020-04-10 2023-05-18 Bristol-Myers Squibb Company Crystalline forms of (9r, 135s)-13- {4-[5-chloro-2-(4-chloro-1h,2,3- triazol- 1 -yl)phenyl] -6-oxo- 1,6-dihydropyrimidin- 1-yl}-3-(difluoromethyl)-9-methyl-3,4,7,15- tetraazatricyclo [ 12.3.1.0 2·6] octadeca- 1(18), 2(6), 4, 14, 16-pentaen-8-one
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
JP7517964B2 (ja) * 2020-11-27 2024-07-17 シャープ株式会社 電子機器、電子機器の制御方法、プログラム、記録媒体
CN112608274B (zh) * 2020-12-30 2022-09-06 西南大学 一种手性胺化合物的催化合成方法及其化合物
KR20230142724A (ko) * 2021-01-08 2023-10-11 브리스톨-마이어스 스큅 컴퍼니 인자 XIa 억제제에 대한 항체 및 항원 결합 펩티드및 그의 용도
CN112876461B (zh) * 2021-01-20 2022-12-30 上海零诺生物科技有限公司 尼古丁及其中间体的制备方法
CN115215867B (zh) * 2021-04-21 2023-12-26 上海美悦生物科技发展有限公司 FXIa抑制剂及其药物组合物、制备方法和用途
CN118973564A (zh) * 2022-02-03 2024-11-15 D·E·萧尔研究有限责任公司 作为trpa1抑制剂的哒嗪酮化合物
JP2025524358A (ja) * 2022-06-08 2025-07-30 ブロッサムヒル・セラピューティクス・インコーポレイテッド インダゾール大員環およびその使用
TW202515882A (zh) * 2023-06-30 2025-04-16 大陸商深圳信立泰藥業股份有限公司 一種多取代的大環化合物及其製備方法與應用
WO2025224678A1 (en) 2024-04-25 2025-10-30 Assia Chemical Industries Ltd. Solid state forms of milvexian and process for preparation thereof

Family Cites Families (110)

* 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
AU717298B2 (en) 1996-04-03 2000-03-23 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
BRPI9909660B8 (pt) 1998-03-19 2021-05-25 Vertex Pharma compostos inibidores de caspases, composição farmacêutica e uso de ditos compostos
CN1138778C (zh) 1998-05-26 2004-02-18 沃尼尔·朗伯公司 用作细胞增殖抑制剂的二环嘧啶及二环3,4-二氢嘧啶化合物及用途
US6307049B1 (en) 1998-09-30 2001-10-23 The Procter & Gamble Co. Heterocyclic 2-substituted ketoamides
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)
WO2000040571A1 (en) 1999-01-02 2000-07-13 Aventis Pharma Deutschland Gmbh Novel malonic acid derivatives, processes for their preparation, their use and pharmaceutical compositions containing them (inhibition of factor xa activity)
SK14232001A3 (sk) 1999-04-09 2002-06-04 Basf Aktiengesellschaft Nízkomolekulové inhibítory komplementárnych proteáz
WO2000076970A2 (en) 1999-06-14 2000-12-21 Eli Lilly And Company Serine protease inhibitors
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
WO2001085695A1 (en) 2000-05-11 2001-11-15 Bristol-Myers Squibb Co. 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
ES2329881T3 (es) 2001-09-21 2009-12-02 Bristol-Myers Squibb Company Compuestos que contienen lactama y derivados de los mismos como inhibidores del factor xa.
AU2002357692A1 (en) 2001-11-09 2003-05-26 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
JP2007501844A (ja) 2003-08-08 2007-02-01 トランス　テック　ファーマ，インコーポレイテッド アリール及びヘテロアリール化合物、組成物並びに使用方法
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
EA200700225A1 (ru) 2004-07-12 2008-02-28 Айдан Фармасьютикалз, Инк. Аналоги тетрапептида
JP5236293B2 (ja) 2005-01-13 2013-07-17 ブリストル−マイヤーズ スクイブ カンパニー Ｘｉａ因子阻害剤としての置換ビアリール化合物
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
US20070111947A1 (en) 2005-10-14 2007-05-17 Mcmurry Thomas J 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
AR058379A1 (es) 2005-12-14 2008-01-30 Bristol Myers Squibb Co Derivados de arilpropionamida arilacrilamida arilpropinamida o arilmetilurea como inhibidores del factor xia. proceso de obtencion y composiciones farmaceuticas.
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
AR058380A1 (es) 2005-12-23 2008-01-30 Bristol Myers Squibb Co Inhibidores del factor viia macrociclicos utiles como anticoagulantes
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
CN101605779B (zh) 2006-12-15 2013-11-20 百时美施贵宝公司 作为凝血因子xia抑制剂的芳基丙酰胺、芳基丙烯酰胺、芳基丙炔酰胺或芳基甲基脲类似物
PE20081775A1 (es) 2006-12-20 2008-12-18 Bristol Myers Squibb Co Compuestos macrociclicos como inhibidores del factor viia
MX2009012847A (es) 2007-06-13 2009-12-08 Bristol Myers Squibb Co Analogos dipeptidicos como inhibidores de factores de coagulacion.
CN102026996B (zh) 2008-03-13 2015-01-07 百时美施贵宝公司 作为凝血因子xia抑制剂的哒嗪衍生物
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
AR077695A1 (es) 2009-08-04 2011-09-14 Schering Corp Derivados de pirimidina como inhibidores del factor ixa
EP2475654B1 (en) * 2009-09-09 2016-12-28 E. I. du Pont de Nemours and Company Herbicidal pyrimidone derivatives
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
US9161924B2 (en) 2011-07-08 2015-10-20 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
EP2766347B1 (en) 2011-10-14 2016-05-04 Bristol-Myers Squibb Company Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
EP3309148A1 (en) 2011-10-14 2018-04-18 Bristol-Myers Squibb Company Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
EP2899183B1 (en) 2011-10-14 2018-09-19 Bristol-Myers Squibb Company Substituted Tetrahydroisoquinoline Compounds as Factor Xia Inhibitors
GB2497806A (en) 2011-12-21 2013-06-26 Ono Pharmaceutical Co Pyridinone and pyrimidinone derivatives as factor XIa inhibitors
EP2794597B1 (en) * 2011-12-21 2017-11-15 ONO Pharmaceutical Co., Ltd. Pyridinone and pyrimidinone derivatives as factor xia inhibitors
WO2013111108A1 (en) 2012-01-27 2013-08-01 Novartis Ag 5-membered heteroarylcarboxamide derivatives as plasma kallikrein inhibitors
WO2013111107A1 (en) 2012-01-27 2013-08-01 Novartis Ag Aminopyridine 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
SG10201609322QA (en) 2012-05-10 2017-01-27 Bayer Pharma AG 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
JP6220786B2 (ja) 2012-07-19 2017-10-25 大日本住友製薬株式会社 １−（シクロアルキルカルボニル）プロリン誘導体
EA028581B1 (ru) * 2012-08-03 2017-12-29 Бристол-Маерс Сквибб Компани ДИГИДРОПИРИДОН Р1 В КАЧЕСТВЕ ИНГИБИТОРОВ ФАКТОРА XIa
UY34959A (es) 2012-08-03 2014-01-31 Bristol Myers Squibb Company Una Corporación Del Estado De Delaware Dihidropiridona p1 como inhibidores del factor xia
EP2906541B1 (en) 2012-10-12 2017-11-22 Bristol-Myers Squibb Company Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors
DK2906551T3 (en) 2012-10-12 2018-05-22 Bristol Myers Squibb Co CRYSTALLIC FORMS OF A FACTOR XIA INHIBITOR
WO2014059202A1 (en) 2012-10-12 2014-04-17 Bristol-Myers Squibb Company Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors
EP2934538B1 (en) 2012-12-19 2021-03-31 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
US9738655B2 (en) 2013-03-25 2017-08-22 Bristol-Myers Squibb Company Tetrahydroisoquinolines containing substituted azoles as factor XIa inhibitors
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
CN105555767B (zh) 2013-07-23 2018-03-23 拜耳制药股份公司 取代的氧代吡啶衍生物及其作为因子xia/血浆的用途
WO2015044173A1 (de) 2013-09-26 2015-04-02 Bayer Pharma Aktiengesellschaft Substituierte phenylalanin-derivate als faktor xia modulatoren
EP3049403A1 (de) 2013-09-26 2016-08-03 Bayer Pharma Aktiengesellschaft Substituierte phenylalanin-derivate
WO2015044167A1 (de) 2013-09-26 2015-04-02 Bayer Pharma Aktiengesellschaft Substituierte phenylalanin-derivate als faktor xia modulatoren
UY35745A (es) 2013-09-26 2015-04-30 Bayer Pharma AG Derivados sustituidos de fenilalanina
EP3049406A1 (de) 2013-09-26 2016-08-03 Bayer Pharma Aktiengesellschaft Substituierte phenylalanin-derivate und ihre verwendung zur behandlung von thrombotischen / thromboembolischen erkrankungen
EP3049407A1 (de) 2013-09-26 2016-08-03 Bayer Pharma Aktiengesellschaft Substituierte phenylalanin-derivate als faktor xia modulatoren
UY35746A (es) 2013-09-26 2015-04-30 Bayer Pharma AG Derivados de fenilalanina sustituidos
EP3049408A1 (de) 2013-09-26 2016-08-03 Bayer Pharma Aktiengesellschaft Substituierte phenylalanin-derivate
US20160229839A1 (en) 2013-09-27 2016-08-11 Merck Sharp & Dohme Corp. Factor XIa Inhibitors
WO2015054087A1 (en) 2013-10-07 2015-04-16 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
KR20160107322A (ko) 2014-01-14 2016-09-13 다이닛본 스미토모 세이야꾸 가부시끼가이샤 축합 ５－옥사졸리디논 유도체
NO2760821T3 (OSRAM) 2014-01-31 2018-03-10
UY40230A (es) * 2014-01-31 2023-08-15 Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware Macrociclos con grupos P2’ heterocíclicos como inhibidores del factor XIa y composiciones farmacéuticas que los comprenden
EP3102200B1 (en) 2014-02-07 2023-04-05 Exithera Pharmaceuticals Inc. Therapeutic compounds and compositions
WO2015123091A1 (en) 2014-02-11 2015-08-20 Merck Sharp & Dohme Corp. Factor xia inhibitors
EP3104703B1 (en) 2014-02-11 2020-11-18 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
PT3113772T (pt) 2014-03-07 2020-12-15 Biocryst Pharm Inc Pirazois substituídos por trifluorometilo como inibidores de calicreína plasmática humana
WO2015160636A1 (en) 2014-04-16 2015-10-22 Merck Sharp & Dohme Corp. Factor ixa inhibitors
US9808445B2 (en) 2014-04-16 2017-11-07 Merck Sharp & Dohme Corp. Factor IXa inhibitors
GB201409202D0 (en) * 2014-05-23 2014-07-09 Ffei Ltd Improvements in imaging microscope samples
KR20150136294A (ko) 2014-05-27 2015-12-07 주식회사 레고켐 바이오사이언스 인자 ＸＩａ 억제 활성을 가지는 신규한 화합물
EP3148542B1 (en) 2014-05-28 2019-02-27 Merck Sharp & Dohme Corp. Factor xia inhibitors
WO2016046157A1 (de) 2014-09-24 2016-03-31 Bayer Pharma Aktiengesellschaft Faktor xia hemmende pyridobenzazepin- und pyridobenzazocin-derivate
US9453018B2 (en) * 2014-10-01 2016-09-27 Bristol-Myers Squibb Company Pyrimidinones as factor XIa inhibitors
NO2721243T3 (OSRAM) * 2014-10-01 2018-10-20
EP3231803B1 (en) 2014-12-10 2020-07-01 ONO Pharmaceutical Co., Ltd. Dihydroindolizinone derivative
EP3310777B1 (en) 2015-06-19 2019-10-09 Bristol-Myers Squibb Company Diamide macrocycles as factor xia inhibitors

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