CA2679175C - Indole and indoline cyclopropyl amide derivatives as ep4 receptor antagonists - Google Patents

Indole and indoline cyclopropyl amide derivatives as ep4 receptor antagonists Download PDF

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Publication number
CA2679175C
CA2679175C CA2679175A CA2679175A CA2679175C CA 2679175 C CA2679175 C CA 2679175C CA 2679175 A CA2679175 A CA 2679175A CA 2679175 A CA2679175 A CA 2679175A CA 2679175 C CA2679175 C CA 2679175C
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CA
Canada
Prior art keywords
pharmaceutically acceptable
formula
acceptable salt
compounds
compound according
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.)
Expired - Fee Related
Application number
CA2679175A
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English (en)
French (fr)
Other versions
CA2679175A1 (en
Inventor
Michael Boyd
John Colucci
Yongxin Han
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.)
Merck Canada Inc
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Merck Canada Inc
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Publication of CA2679175A1 publication Critical patent/CA2679175A1/en
Application granted granted Critical
Publication of CA2679175C publication Critical patent/CA2679175C/en
Expired - Fee Related legal-status Critical Current
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic 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
    • 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
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • 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
    • C07D403/12—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 chain containing hetero atoms as chain links

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  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Vascular Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Indole Compounds (AREA)
CA2679175A 2007-02-26 2008-02-22 Indole and indoline cyclopropyl amide derivatives as ep4 receptor antagonists Expired - Fee Related CA2679175C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US90349407P 2007-02-26 2007-02-26
US60/903,494 2007-02-26
PCT/CA2008/000351 WO2008104055A1 (en) 2007-02-26 2008-02-22 Indole and indoline cyclopropyl amide derivatives as ep4 receptor antagonists

Publications (2)

Publication Number Publication Date
CA2679175A1 CA2679175A1 (en) 2008-09-04
CA2679175C true CA2679175C (en) 2015-01-13

Family

ID=39720805

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2679175A Expired - Fee Related CA2679175C (en) 2007-02-26 2008-02-22 Indole and indoline cyclopropyl amide derivatives as ep4 receptor antagonists

Country Status (8)

Country Link
US (1) US8158671B2 (enExample)
EP (1) EP2114877B1 (enExample)
JP (1) JP5301469B2 (enExample)
CN (1) CN101622230B (enExample)
AU (1) AU2008221194B2 (enExample)
CA (1) CA2679175C (enExample)
ES (1) ES2400293T3 (enExample)
WO (1) WO2008104055A1 (enExample)

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US8110585B2 (en) 2007-04-26 2012-02-07 Takeda Pharmaceutical Company Limited Bicyclic compound and pharmaceutical use thereof
SI2565191T1 (sl) 2008-05-14 2014-12-31 Astellas Pharma Inc. Derivati 4-(indol-7-ilkarbonilaminometil)cikloheksan karboksilne kisline kot EP4 receptorski antagonisti, uporabni za zdravljenje kronične ledvične odpovedi ali diabetične nefropatije
EP2320906B1 (en) * 2008-08-14 2016-02-24 Beta Pharma Canada Inc. Heterocyclic amide derivatives as ep4 receptor antagonists
WO2010087425A1 (ja) 2009-01-30 2010-08-05 国立大学法人京都大学 前立腺癌の進行抑制剤および進行抑制方法
WO2010121382A1 (en) * 2009-04-21 2010-10-28 Merck Frosst Canada Ltd. Process for making indole cyclopropyl amide derivatives
EA023788B1 (ru) * 2010-05-07 2016-07-29 ГЛЭКСОСМИТКЛАЙН ЭлЭлСи Производные индола и фармацевтические композиции на их основе
PH12013500467A1 (en) 2010-09-21 2013-04-29 Eisai R&D Man Co Ltd Pharmaceutical composition
CA2820109C (en) 2010-12-10 2018-01-09 Rottapharm S.P.A. Pyridine amide derivatives as ep4 receptor antagonists
EP2729141B1 (en) 2011-07-04 2015-12-09 Rottapharm Biotech S.r.l. Cyclic amine derivatives as ep4 receptor agonists
US9181279B2 (en) 2011-07-04 2015-11-10 Rottapharm Biotech S.R.L. Cyclic amine derivatives as EP4 receptor antagonists
UA115576C2 (uk) 2012-12-06 2017-11-27 Байєр Фарма Акцієнгезелльшафт Похідні бензимідазолу як антагоністи ер4
US9295665B2 (en) 2013-03-12 2016-03-29 Allergan, Inc. Inhibition of neovascularization by simultaneous inhibition of prostanoid IP and EP4 receptors
PT3009426T (pt) 2013-06-12 2018-06-08 Kaken Pharma Co Ltd Derivado de 4-alquinilimidazole e medicamento compreendendo o mesmo como ingrediente ativo
TW201607943A (zh) 2013-12-19 2016-03-01 拜耳製藥公司 作為ｅｐ４配體之新穎苯并咪唑衍生物
MX390051B (es) 2015-10-16 2025-03-20 Eisai R&D Man Co Ltd Antagonistas de ep4.
CR20180323A (es) 2015-11-20 2018-08-06 Idorsia Pharmaceuticals Ltd Derivados de indol n-sustituídos como moduladores de los receptores de pge2
TWI795362B (zh) 2016-07-07 2023-03-11 日商小野藥品工業股份有限公司 拮抗藥與免疫核查點阻礙藥而成之組合
WO2018162562A1 (en) 2017-03-10 2018-09-13 Bayer Pharma Aktiengesellschaft Use of an ep4 antagonist for the treatment of inflammatory pain
US11066405B2 (en) * 2017-04-18 2021-07-20 Tempest Therapeutics, Inc. Bicyclic compounds and their use in the treatment of cancer
AU2018255300B2 (en) * 2017-04-18 2021-10-28 Tempest Therapeutics, Inc. Bicyclic compounds and their use in the treatment of cancer
MX388257B (es) 2017-05-18 2025-03-19 Idorsia Pharmaceuticals Ltd Derivados de pirimidina como moduladores del receptor de pge2.
AR111941A1 (es) 2017-05-18 2019-09-04 Idorsia Pharmaceuticals Ltd Derivados de pirimidina como moduladores del receptor de pge2
JP7093791B2 (ja) 2017-05-18 2022-06-30 イドーシア ファーマシューティカルズ リミテッド Ｐｇｅ２レセプター調節剤としてのベンゾフラン及びベンゾチオフェン誘導体
US20200069686A1 (en) 2017-05-18 2020-03-05 Idorsia Pharmaceuticals Ltd N-substituted indole derivatives
EP3625223B1 (en) 2017-05-18 2021-08-11 Idorsia Pharmaceuticals Ltd Pyrimidine derivatives
WO2019038156A1 (en) 2017-08-22 2019-02-28 Bayer Pharma Aktiengesellschaft USE OF AN EP4 ANTAGONIST FOR THE TREATMENT OF ARTHRITIS
CA3092310C (en) 2018-03-02 2024-01-02 Shenzhen Ionova Life Science Co., Ltd. Heterobicyclic carboxylic acids and salts thereof
KR102815312B1 (ko) 2018-04-17 2025-05-30 템페스트 테라퓨틱스, 인크. 비시클릭 카르복스아미드 및 그의 사용 방법
ES2948293T3 (es) 2018-07-12 2023-09-07 Rottapharm Biotech Srl Acido (R)-4-(1-(1-(4-(trifluorometil)bencil)pirrolidina-2-carboxamida)ciclopropil)-benzoico como antagonista del receptor EP4
KR102861190B1 (ko) * 2019-01-22 2025-09-17 키테라 (쑤저우) 바이오-파마슈티컬스 컴퍼니 리미티드 Pge2/ep4 신호 전달을 억제하기 위한 화합물, 이의 제조 방법, 및 이의 의약적 용도
EP3722319A1 (en) 2019-04-09 2020-10-14 Rottapharm Biotech S.r.l. Pharmaceutical combination of an ep4 antagonist and immune checkpoint inhibitors for the treatment of tumours
EP3827828A1 (en) 2019-11-29 2021-06-02 Rottapharm Biotech S.r.l. (r)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)-cyclopropyl) benzoic acid or its salt also in polymorphic form a for use in the prevention of heterotopic ossification
WO2021115560A1 (en) 2019-12-09 2021-06-17 Rottapharm Biotech S.R.L. New fyn and vegfr2 kinase inhibitors
EP3885339A1 (en) 2020-03-27 2021-09-29 Rottapharm Biotech S.r.l. Process for the preparation of (r)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)-cyclopropyl) benzoic acid or a salt thereof
EP4245301A4 (en) 2020-11-13 2024-08-21 ONO Pharmaceutical Co., Ltd. TREATMENT OF CANCER BY COMBINED USE OF AN EP4 ANTAGONIST AND AN IMMUNE CHECKPOINT INHIBITOR
CN117377471A (zh) * 2021-05-28 2024-01-09 凯复(苏州)生物医药有限公司 治疗肿瘤的联合疗法
WO2022257960A1 (zh) * 2021-06-08 2022-12-15 武汉人福创新药物研发中心有限公司 用于治疗ep2、ep4受体介导的疾病的双环化合物
EP4393906A4 (en) * 2021-08-27 2026-03-04 Keythera Suzhou Bio Pharmaceuticals Co Ltd Solid form of an indole compound, method of manufacture thereof and use thereof

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MXPA02008801A (es) * 2000-03-09 2003-07-07 Ono Pharmaceutical Co Derivados de indol, proceso para la preparacion de los mismos y su uso.
JP2003528144A (ja) * 2000-03-24 2003-09-24 ファーマジーン ラボラトリーズ リミテッド 頭痛治療のためのプロスタノイドｅｐ４受容体アンタゴニストの使用およびそのアンタゴニストについてのアッセイ
CA2415742A1 (en) * 2000-07-25 2002-01-31 Merck & Co., Inc. N-substituted indoles useful in the treatment of diabetes
RS20060143A (sr) * 2003-09-03 2008-06-05 Pfizer Inc., Jedinjenja fenil ili piridil amida kao antagonisti prostaglandina e2
ATE533766T1 (de) * 2005-05-19 2011-12-15 Merck Canada Inc Chinolinderivate als ep4-antagonisten
CA2648729A1 (en) * 2006-04-24 2007-11-01 Merck Frosst Canada Ltd. Indole amide derivatives as ep4 receptor antagonists
US7705035B2 (en) * 2006-06-12 2010-04-27 Merck Frosst Canada Ltd. Indoline amide derivatives as EP4 receptor ligands

Also Published As

Publication number Publication date
CN101622230B (zh) 2012-08-22
US20090318518A1 (en) 2009-12-24
EP2114877B1 (en) 2012-12-26
EP2114877A4 (en) 2010-10-27
AU2008221194B2 (en) 2013-06-27
ES2400293T3 (es) 2013-04-08
WO2008104055A1 (en) 2008-09-04
JP2010519260A (ja) 2010-06-03
AU2008221194A1 (en) 2008-09-04
CN101622230A (zh) 2010-01-06
US8158671B2 (en) 2012-04-17
JP5301469B2 (ja) 2013-09-25
EP2114877A1 (en) 2009-11-11
CA2679175A1 (en) 2008-09-04

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Effective date: 20130208

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