CN109689664B - 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 - Google Patents

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 Download PDF

Info

Publication number
CN109689664B
CN109689664B CN201780056459.5A CN201780056459A CN109689664B CN 109689664 B CN109689664 B CN 109689664B CN 201780056459 A CN201780056459 A CN 201780056459A CN 109689664 B CN109689664 B CN 109689664B
Authority
CN
China
Prior art keywords
thiazol
methoxy
methylquinoxalin
methyl
benzo
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
CN201780056459.5A
Other languages
English (en)
Chinese (zh)
Other versions
CN109689664A (zh
Inventor
张晓军
E·S·普里斯特利
O·S·哈尔彭
蒋文
S·K·列兹尼克
J·M·里希特
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 CN109689664A publication Critical patent/CN109689664A/zh
Application granted granted Critical
Publication of CN109689664B publication Critical patent/CN109689664B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D519/00Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/4965Non-condensed pyrazines
    • A61K31/497Non-condensed pyrazines containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D493/00Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D513/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D515/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D515/12Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
    • C07D515/14Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CN201780056459.5A 2016-07-14 2017-07-13 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 Active CN109689664B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662362121P 2016-07-14 2016-07-14
US62/362,121 2016-07-14
PCT/US2017/041880 WO2018013776A1 (en) 2016-07-14 2017-07-13 Tricyclic heteroaryl-substituted quinoline and azaquinoline compounds as par4 inhibitors

Publications (2)

Publication Number Publication Date
CN109689664A CN109689664A (zh) 2019-04-26
CN109689664B true CN109689664B (zh) 2022-04-15

Family

ID=59384259

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201780056459.5A Active CN109689664B (zh) 2016-07-14 2017-07-13 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

Country Status (7)

Country Link
US (3) US20190315774A1 (enExample)
EP (1) EP3484894B1 (enExample)
JP (1) JP6903732B2 (enExample)
KR (1) KR102468661B1 (enExample)
CN (1) CN109689664B (enExample)
ES (1) ES2823127T3 (enExample)
WO (1) WO2018013776A1 (enExample)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7102388B2 (ja) * 2016-07-14 2022-07-19 ブリストル-マイヤーズ スクイブ カンパニー 単環式ヘテロアリール置換化合物
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
CN109689647B (zh) 2016-07-14 2023-01-20 百时美施贵宝公司 二环杂芳基取代的化合物
US10730868B2 (en) 2016-07-14 2020-08-04 Bristol-Myers Squibb Company Bicyclic heteroaryl substituted compounds
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
CN117285527A (zh) * 2023-09-25 2023-12-26 中国药科大学 一种噌啉类par4拮抗剂及其医药应用

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1982001706A1 (en) * 1980-11-11 1982-05-27 Tominaga Michiaki Carbostyril compounds,composition containing same,and process for their preparation
EP0534443A1 (en) * 1991-09-26 1993-03-31 Mitsubishi Chemical Corporation 3,6-Disubstituted pyridazine derivatives
WO2013163241A1 (en) * 2012-04-26 2013-10-31 Bristol-Myers Squibb Company Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (par4) inhibitors for treating platelet aggregation
WO2015077550A1 (en) * 2013-11-22 2015-05-28 University Of Kentucky Research Foundation Arylquinoline and analog compounds and use thereof to treat cancer
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
WO2018013770A1 (en) * 2016-07-14 2018-01-18 Bristol-Myers Squibb Company Bicyclic heteroaryl substituted compounds

Family Cites Families (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
US6166041A (en) 1995-10-11 2000-12-26 Euro-Celtique, S.A. 2-heteroaryl and 2-heterocyclic benzoxazoles as PDE IV inhibitors for the treatment of asthma
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
EP1348701A1 (en) 2002-03-28 2003-10-01 Warner-Lambert Company LLC (2,4-disubstituted-thiazol-5-yl) amine compounds as PDE7 inhibitors
BRPI0413234A (pt) 2003-08-01 2006-10-03 Genelabs Tech Inc derivados de imidazola bicìclica contra flaviviridae
WO2005113522A1 (en) 2004-05-07 2005-12-01 Janssen Pharmaceutica, N.V. Azole carboxamide inhibitors of bacterial type iii protein secretion systems
KR20070046150A (ko) 2004-07-28 2007-05-02 아이알엠 엘엘씨 스테로이드 호르몬 핵 수용체의 조절제로서의 화합물 및조성물
AU2006204917A1 (en) 2005-01-14 2006-07-20 Smithkline Beecham Corporation Indole derivatives for treating viral infections
US20080015193A1 (en) 2006-06-20 2008-01-17 Mendoza Jose S Certain azoles exhibiting ATP-utilizing enzyme inhibitory activity, compositions, and uses thereof
WO2008000643A1 (en) 2006-06-29 2008-01-03 F. Hoffmann-La Roche Ag Benzimidazole derivatives, method for the production thereof, their use as fxr agonists and pharmaceutical preparations containing the same
WO2008073451A2 (en) 2006-12-11 2008-06-19 Sirtris Pharmaceuticals, Inc. Benzoimidazole derivatives as sirtuin (sir) modulating compounds
JP2011508725A (ja) 2007-11-30 2011-03-17 グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー プロリルヒドロキシラーゼ阻害剤
JP5425891B2 (ja) 2008-05-01 2014-02-26 サートリス ファーマシューティカルズ, インコーポレイテッド サーチュイン調節薬としてのキノリンおよび関連する類似体
MY155535A (en) 2008-05-23 2015-10-30 Novartis Ag Derivatives of quinolines and quinoxalines as protien tyrosine kinase inhibitors
JP5631310B2 (ja) 2008-07-23 2014-11-26 バーテックス ファーマシューティカルズ インコーポレイテッドVertex Pharmaceuticals Incorporated 三環式ピラゾロピリジンキナーゼ阻害剤
US20130072473A1 (en) 2011-05-09 2013-03-21 Proteostasis Therapeutics, Inc. Compounds for treating protein folding disorders
WO2013130660A1 (en) 2012-02-28 2013-09-06 Amgen Inc. Amides as pim inhibitors
MX2014012454A (es) * 2012-04-26 2015-03-13 Bristol Myers Squibb Co Derivados de imidazotiadiazol como inhibidores del receptor 4 activado de proteasa (par4) para el tratamiento de agregacion plaquetaria.
PT2841437T (pt) 2012-04-26 2017-09-28 Univ Montreal Derivados de imidazotiadiazol e imidazopirazina como inibidores de recetor 4 ativado por protease (par4) para o tratamento de agregação plaquetária
US9598419B1 (en) 2014-06-24 2017-03-21 Universite De Montreal Imidazotriazine and imidazodiazine compounds
US9617279B1 (en) 2014-06-24 2017-04-11 Bristol-Myers Squibb Company Imidazooxadiazole compounds
ES2929208T3 (es) 2015-02-26 2022-11-25 Univ Montreal Compuestos de imidazotiadiazol como inhibidores de PAR4
WO2016138199A1 (en) 2015-02-26 2016-09-01 Bristol-Myers Squibb Company Benzothiazole and benzothiophne 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
JP7102388B2 (ja) 2016-07-14 2022-07-19 ブリストル-マイヤーズ スクイブ カンパニー 単環式ヘテロアリール置換化合物

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1982001706A1 (en) * 1980-11-11 1982-05-27 Tominaga Michiaki Carbostyril compounds,composition containing same,and process for their preparation
EP0534443A1 (en) * 1991-09-26 1993-03-31 Mitsubishi Chemical Corporation 3,6-Disubstituted pyridazine derivatives
WO2013163241A1 (en) * 2012-04-26 2013-10-31 Bristol-Myers Squibb Company Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (par4) inhibitors for treating platelet aggregation
WO2015077550A1 (en) * 2013-11-22 2015-05-28 University Of Kentucky Research Foundation Arylquinoline and analog compounds and use thereof to treat cancer
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
WO2018013770A1 (en) * 2016-07-14 2018-01-18 Bristol-Myers Squibb Company Bicyclic heteroaryl substituted compounds

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Studies on the Chemical constituents of Rutaceous Plants.XXXVI.Synthesis of Ethyl Isodecarine;HISASHI ISHII et al.;《Chem. Phem. Bull》;19771231;第514-519页 *
Substituted indoles as selective protease activated receptor 4 (PAR-4)antagonists: Discovery and SAR of ML354;Wandong Wen et al.;《Bioorganic & Medicinal Chemistry Letters》;20140815;第4708-4713页 *

Also Published As

Publication number Publication date
ES2823127T3 (es) 2021-05-06
US11932658B2 (en) 2024-03-19
JP2019524732A (ja) 2019-09-05
CN109689664A (zh) 2019-04-26
US20190315774A1 (en) 2019-10-17
KR102468661B1 (ko) 2022-11-17
EP3484894A1 (en) 2019-05-22
KR20190026906A (ko) 2019-03-13
US20210188877A1 (en) 2021-06-24
JP6903732B2 (ja) 2021-07-14
EP3484894B1 (en) 2020-08-19
WO2018013776A1 (en) 2018-01-18
US20240309019A1 (en) 2024-09-19
US12528827B2 (en) 2026-01-20

Similar Documents

Publication Publication Date Title
CN109689664B (zh) 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
TWI874443B (zh) KRas G12D抑制劑
CN109689649B (zh) 经二环杂芳基取代的化合物
CN109689647B (zh) 二环杂芳基取代的化合物
CN115551867A (zh) 稠合三环类化合物、其药物组合物及用途
CN103562210B (zh) 对pI3K 110δ具有选择性的苯并氧氮杂*化合物及使用方法
CN105916855B (zh) 作为酪蛋白激酶1d/e抑制剂的取代的4,5,6,7-四氢吡唑并[1,5-a]吡嗪衍生物
EP3964516A1 (en) Oxaazaquinazoline-7(8h)-ketone compound, preparation method therfor and pharmaceutical application thereof
JP2020518601A (ja) ヒト免疫不全ウイルス複製の阻害剤
WO2023138583A1 (zh) 杂环类化合物、药物组合物及其应用
CN107709322B (zh) 作为抗癌剂的三环化合物
KR102794736B1 (ko) 트리아졸로피리다진 유도체, 이의 제조 방법, 약물 조성물 및 용도
US20240018161A1 (en) Modulators of cystic fibrosis transmembrane conductance regulator
CN102459272A (zh) 对P110δ具有选择性的为PI3K抑制剂的二环嘧啶化合物和使用方法
CN109689642B (zh) 经单环杂芳基取代的化合物
JP6954920B2 (ja) ブロモドメイン阻害薬としてのベンゾ[b]フラン
CN114980975A (zh) 二氢环戊二烯并异喹啉磺酰胺衍生物
CN118401516A (zh) Tyk2抑制剂及其组合物和方法
JP2021527102A (ja) ガレクチン−3抑制剤を模したテトラヒドロピラン系チオ二糖類
CN116731016A (zh) 作为iap拮抗剂的三环杂环化合物
CN121443603A (zh) 能够用于治疗smarca4缺失型癌症的作为smarca2抑制剂的1,6-萘啶化合物
CN115551855A (zh) 半乳凝素-3的小分子抑制剂
HK40094579A (zh) 作为iap拮抗剂的三环杂环化合物
CN115551850A (zh) 半乳凝素-3的小分子抑制剂
HK40076948A (en) Kras g12d inhibitors

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant