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)
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CA2679175A1 (en
Inventor
Michael Boyd
John Colucci
Yongxin Han
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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
Anticipated expiration legal-status Critical

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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)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (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 (OSRAM)
EP (1) EP2114877B1 (OSRAM)
JP (1) JP5301469B2 (OSRAM)
CN (1) CN101622230B (OSRAM)
AU (1) AU2008221194B2 (OSRAM)
CA (1) CA2679175C (OSRAM)
ES (1) ES2400293T3 (OSRAM)
WO (1) WO2008104055A1 (OSRAM)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2141150B1 (en) 2007-04-26 2013-12-11 Takeda Pharmaceutical Company Limited Bicyclic compound and pharmaceutical use thereof
RU2479576C9 (ru) 2008-05-14 2014-03-10 Астеллас Фарма Инк. Амидное соединение
EP2320906B1 (en) * 2008-08-14 2016-02-24 Beta Pharma Canada Inc. Heterocyclic amide derivatives as ep4 receptor antagonists
JPWO2010087425A1 (ja) 2009-01-30 2012-08-02 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
EP2566327B1 (en) * 2010-05-07 2017-03-29 Glaxosmithkline LLC Indoles
SMT201700008T1 (it) 2010-09-21 2017-03-08 Eisai R&D Man Co Ltd Composizione farmaceutica
ES2545110T3 (es) 2010-12-10 2015-09-08 Rottapharm Biotech S.R.L. Derivados de piridinamida como antagonistas del receptor EP4
US9120824B2 (en) 2011-07-04 2015-09-01 Rottapharm Biotech S.R.L. Cyclic amine derivatives as EP4 receptor agonists
DK2729445T3 (en) 2011-07-04 2016-01-18 Rottapharm Biotech Srl CYCLIC AMINE DERIVATIVES AS EP4 RECEPTOR ANTAGONISTS
UA115576C2 (uk) 2012-12-06 2017-11-27 Байєр Фарма Акцієнгезелльшафт Похідні бензимідазолу як антагоністи ер4
WO2014143591A1 (en) 2013-03-12 2014-09-18 Allergan, Inc. Inhibition of neovascularization by simultaneous inhibition of prostanoid ip and ep4 receptors
HUE039015T2 (hu) 2013-06-12 2018-12-28 Kaken Pharma Co Ltd 4-Alkinil-imidazol-származék és ezt hatóanyagként tartalmazó gyógyszerkészítmény
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
CA3002144C (en) 2015-10-16 2024-01-23 Eisai R&D Management Co., Ltd. Ep4 antagonists
CR20180323A (es) 2015-11-20 2018-08-06 Idorsia Pharmaceuticals Ltd Derivados de indol n-sustituídos como moduladores de los receptores de pge2
AU2017292522B2 (en) * 2016-07-07 2022-10-13 Ono Pharmaceutical Co., Ltd. Combination comprising EP4 antagonist and immune checkpoint inhibitor
WO2018162562A1 (en) 2017-03-10 2018-09-13 Bayer Pharma Aktiengesellschaft Use of an ep4 antagonist for the treatment of inflammatory pain
ES2914311T3 (es) * 2017-04-18 2022-06-09 Tempest Therapeutics Inc Compuestos bicíclicos y su uso en el tratamiento del cáncer
US11066405B2 (en) * 2017-04-18 2021-07-20 Tempest Therapeutics, Inc. Bicyclic compounds and their use in the treatment of cancer
US11325899B2 (en) 2017-05-18 2022-05-10 Idorsia Pharmaceuticals Ltd Benzofurane and benzothiophene derivatives as PGE2 receptor modulators
AU2018268311B2 (en) 2017-05-18 2022-02-10 Idorsia Pharmaceuticals Ltd Pyrimidine derivatives as PGE2 receptor modulators
WO2018210992A1 (en) 2017-05-18 2018-11-22 Idorsia Pharmaceuticals Ltd Pyrimidine derivatives
EP3625224B1 (en) 2017-05-18 2021-08-04 Idorsia Pharmaceuticals Ltd N-substituted indole derivatives
WO2018210994A1 (en) 2017-05-18 2018-11-22 Idorsia Pharmaceuticals Ltd Phenyl derivatives as pge2 receptor modulators
WO2019038156A1 (en) 2017-08-22 2019-02-28 Bayer Pharma Aktiengesellschaft USE OF AN EP4 ANTAGONIST FOR THE TREATMENT OF ARTHRITIS
EP3759114A4 (en) * 2018-03-02 2021-12-15 Shenzhen Ionova Life Science Co., Ltd. HETEROBICYCLIC CARBOXYLIC ACIDS AND THEIR SALTS
KR102815312B1 (ko) 2018-04-17 2025-05-30 템페스트 테라퓨틱스, 인크. 비시클릭 카르복스아미드 및 그의 사용 방법
AU2019300449A1 (en) * 2018-07-12 2021-03-04 Rottapharm Biotech S.R.L. (R)-4-(1-(1-(4-(trifluoromethyl)benzyl)pyrrolidine-2-carboxamide)cyclopropyl)-benzoic acid as EP4 receptor antagonist
JP7488269B2 (ja) * 2019-01-22 2024-05-21 キーセラ・（スーチョウ）・ファーマシューティカルズ・カンパニー・リミテッド Ｐｇｅ２／ｅｐ４シグナル伝達を阻害する化合物、その製造方法及びその医薬における応用
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
WO2022102731A1 (ja) 2020-11-13 2022-05-19 小野薬品工業株式会社 Ｅｐ４拮抗薬と免疫チェックポイント阻害物質との併用によるがん治療
WO2022247881A1 (zh) * 2021-05-28 2022-12-01 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
EP4393906A1 (en) * 2021-08-27 2024-07-03 Keythera (Suzhou) Bio-Pharmaceuticals Co., Limited Solid form of indole compound, preparation method therefor and use thereof

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ521192A (en) 2000-03-09 2005-01-28 Ono Pharmaceutical Co Indole derivatives, process for preparation of the same and use thereof
AU2000234451B2 (en) * 2000-03-24 2005-09-29 Asterand Uk Acquisition Limited Use of prostanoid ep4 receptor antagonists for the treatment of headache and assays for such antagonists
WO2002008188A1 (en) 2000-07-25 2002-01-31 Merck & Co., Inc. N-substituted indoles useful in the treatment of diabetes
CA2536870C (en) * 2003-09-03 2009-10-27 Pfizer Inc. Phenyl or pyridyl amide compounds as prostaglandin e2 antagonists
JP5289046B2 (ja) * 2005-05-19 2013-09-11 メルク カナダ インコーポレイテッド Ｅｐ４アンタゴニストとしてのキノリン誘導体
WO2007121578A1 (en) * 2006-04-24 2007-11-01 Merck Frosst Canada Ltd. Indole amide derivatives as ep4 receptor antagonists
AU2007260529B2 (en) * 2006-06-12 2012-04-19 Merck Canada Inc. Indoline amide derivatives as EP4 receptor ligands

Also Published As

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

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