CN109689642B - 经单环杂芳基取代的化合物 - Google Patents

经单环杂芳基取代的化合物 Download PDF

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CN109689642B
CN109689642B CN201780055447.0A CN201780055447A CN109689642B CN 109689642 B CN109689642 B CN 109689642B CN 201780055447 A CN201780055447 A CN 201780055447A CN 109689642 B CN109689642 B CN 109689642B
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methylquinoxalin
difluoromethoxy
mmol
thiazole
reaction mixture
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CN109689642A (zh
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J·M·里克特
张晓军
E·S·普利斯特列
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Bristol Myers Squibb Co
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—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
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • 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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D403/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D403/10—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 aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 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
    • C07D471/02—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
    • C07D471/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hematology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
CN201780055447.0A 2016-07-14 2017-07-13 经单环杂芳基取代的化合物 Active CN109689642B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662362081P 2016-07-14 2016-07-14
US62/362,081 2016-07-14
PCT/US2017/041873 WO2018013772A1 (en) 2016-07-14 2017-07-13 Monocyclic heteroaryl substituted compounds

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CN109689642A CN109689642A (zh) 2019-04-26
CN109689642B true CN109689642B (zh) 2022-04-12

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US (1) US10815224B2 (enExample)
EP (1) EP3484874B1 (enExample)
JP (1) JP7102388B2 (enExample)
KR (1) KR102492715B1 (enExample)
CN (1) CN109689642B (enExample)
ES (1) ES2805030T3 (enExample)
WO (1) WO2018013772A1 (enExample)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6990228B2 (ja) 2016-07-14 2022-01-13 ブリストル－マイヤーズ スクイブ カンパニー 二環式ヘテロアリール置換の化合物
CN109689664B (zh) 2016-07-14 2022-04-15 百时美施贵宝公司 作为par4抑制剂的三环杂芳基取代的喹啉和氮杂喹啉化合物
WO2018013774A1 (en) 2016-07-14 2018-01-18 Bristol-Myers Squibb Company Bicyclic heteroaryl substituted compounds
AU2019476916B2 (en) 2019-12-04 2024-02-22 Nec Corporation Abnormal physical condition determination system, abnormal physical condition determination method, and computer program
CN111440146B (zh) * 2020-05-15 2022-10-21 中国药科大学 一种具有par4拮抗活性的苯并三嗪类化合物及其应用
CN116041341B (zh) * 2022-11-24 2025-02-28 中国药科大学 一种喹唑啉类par4拮抗剂及其医药应用
AU2023406476A1 (en) 2022-12-02 2025-06-05 Neumora Therapeutics, Inc. Methods of treating neurological disorders

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0224823A2 (de) * 1985-11-26 1987-06-10 BASF Aktiengesellschaft Chinolinderivate und ihre Verwendung zur Bekämpfung von unerwümschtem Pflanzenwachstum
CN1356991A (zh) * 1998-11-24 2002-07-03 阿温蒂斯药物制品公司 用作pdgf－受体和/或lck酪氨酸激酶抑制剂的喹啉和喹喔啉化合物
WO2004043929A1 (en) * 2002-11-12 2004-05-27 Pfizer Products Inc. Quinoline derivatives
WO2008141065A1 (en) * 2007-05-10 2008-11-20 Smithkline Beecham Corporation Quinoxaline derivatives as p13 kinase inhibitors
CN103814020A (zh) * 2011-06-17 2014-05-21 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4472406A (en) * 1982-11-12 1984-09-18 Riker Laboratories, Inc. Antimicrobial 6,7-dihydro-8-(imidazol-1-yl)-5-methyl-1-oxo-1H,5H-benzo [ij]quinolizine-2-carboxylic acids and derivatives
US4567269A (en) * 1982-11-12 1986-01-28 Riker Laboratories, Inc. Intermediates for the preparation of 6,7-dihydro-8-(imidazol-1-yl)-5-methyl-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylic acids
US4567186A (en) * 1985-01-14 1986-01-28 Sterling Drug Inc. 5-Heteryl-1,6-naphthyridin-2(1H)-ones, cardiotonic use thereof and intermediates therefor
DE3541722A1 (de) * 1985-11-26 1987-05-27 Basf Ag Chinolinderivate und ihre verwendung zur bekaempfung von unerwuenschtem pflanzenwachstum
KR900004213A (ko) * 1988-08-12 1990-03-27 최근선 쌍 방향 송수신의 원격 제어 시스템
US5110347A (en) * 1990-11-26 1992-05-05 E. I Du Pont De Nemours And Company Substituted fused heterocyclic herbicides
JP2928079B2 (ja) 1994-02-14 1999-07-28 永信薬品工業股▲ふん▼有限公司 １−（置換ベンジル）−３−（置換アリール）縮合ピラゾール類、その製造法及びその用途
US5633218A (en) * 1995-05-24 1997-05-27 E. I. Du Pont De Nemours And Company Herbicidal benzodioxoles and benzodioxanes
US6387942B2 (en) 2000-06-19 2002-05-14 Yung Shin Pharmaceutical Ind. Co. Ltd Method of treating disorders related to protease-activated receptors-induced cell activation
US6894062B1 (en) * 2002-11-12 2005-05-17 Pfizer Inc. Quinoline derivatives
US20080015193A1 (en) 2006-06-20 2008-01-17 Mendoza Jose S Certain azoles exhibiting ATP-utilizing enzyme inhibitory activity, compositions, and uses thereof
WO2012054874A1 (en) 2010-10-22 2012-04-26 Intermune, Inc. Novel macrocyclic inhibitors of hepatitis c virus replication
CN102827073A (zh) * 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
TW201348226A (zh) * 2012-02-28 2013-12-01 Amgen Inc 作為ｐｉｍ抑制劑之醯胺
MX2014012741A (es) 2012-04-26 2015-04-13 Bristol Myers Squibb Co Derivados de imidazotiadiazol e imidazopirazina como inhibidores del receptor 4 activado de proteasa (par4) para tratamiento de agregacion plaquetaria.
BR112014026643B1 (pt) 2012-04-26 2023-03-07 Universite De Montreal Derivados de imidazotiadiazol e imidazopirazina como inibidores de receptor 4 ativado por protease (par4) para o tratamento de agregação de plaqueta, seus usos e composição farmacêutica
SG11201406759YA (en) 2012-04-26 2014-11-27 Bristol Myers Squibb Co Imidazothiadiazole derivatives as protease activated receptor 4 (par4) inhibitors for treating platelet aggregation
US9873670B2 (en) 2013-11-22 2018-01-23 University Of Kentucky Research Foundation Arylquinoline and analog compounds and use thereof to treat cancer
ES2929208T3 (es) 2015-02-26 2022-11-25 Univ Montreal Compuestos de imidazotiadiazol como inhibidores de PAR4
WO2017019828A1 (en) * 2015-07-30 2017-02-02 Bristol-Myers Squibb Company Aryl substituted bicyclic heteroaryl compounds
WO2018013774A1 (en) 2016-07-14 2018-01-18 Bristol-Myers Squibb Company Bicyclic heteroaryl substituted compounds
CN109689664B (zh) 2016-07-14 2022-04-15 百时美施贵宝公司 作为par4抑制剂的三环杂芳基取代的喹啉和氮杂喹啉化合物
JP6990228B2 (ja) 2016-07-14 2022-01-13 ブリストル－マイヤーズ スクイブ カンパニー 二環式ヘテロアリール置換の化合物

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0224823A2 (de) * 1985-11-26 1987-06-10 BASF Aktiengesellschaft Chinolinderivate und ihre Verwendung zur Bekämpfung von unerwümschtem Pflanzenwachstum
CN1356991A (zh) * 1998-11-24 2002-07-03 阿温蒂斯药物制品公司 用作pdgf－受体和/或lck酪氨酸激酶抑制剂的喹啉和喹喔啉化合物
WO2004043929A1 (en) * 2002-11-12 2004-05-27 Pfizer Products Inc. Quinoline derivatives
WO2008141065A1 (en) * 2007-05-10 2008-11-20 Smithkline Beecham Corporation Quinoxaline derivatives as p13 kinase inhibitors
CN103814020A (zh) * 2011-06-17 2014-05-21 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
2(lff)-Quinolinones with Cardiac Stimulant Activity. 1. Synthesis and Biological Activities of (Six-Membered Heteroaryl)-Substituted Derivatives;Colin T. Alabaster等;《J. Med. Chem.》;19881231;第31卷;第2048-2056页 *
Discovery of a highly potent series of oxazole-based phosphodiesterase 4 inhibitors;Rongze Kuang等;《Bioorganic & Medicinal Chemistry Letters》;20070707;第17卷;第5150–5154页 *
Novel Synthesis of 7-Fluoro-8-(trifluoromethyl)-1H-1,6-naphthyridin-4-one Derivatives: ...... Pentasubstituted Pyridines;Hiroyuki Suzuki等;《J. Org. Chem.》;20070628;第72卷;第5878-5881页 *

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ES2805030T3 (es) 2021-02-10
KR102492715B1 (ko) 2023-01-26
KR20190026905A (ko) 2019-03-13
JP2019521153A (ja) 2019-07-25
US20190248771A1 (en) 2019-08-15
US10815224B2 (en) 2020-10-27
WO2018013772A1 (en) 2018-01-18
EP3484874B1 (en) 2020-04-29
CN109689642A (zh) 2019-04-26
JP7102388B2 (ja) 2022-07-19
EP3484874A1 (en) 2019-05-22

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