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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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
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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
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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)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Neurology (AREA)
  • Physical Education & Sports Medicine (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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JP5289308B2 (ja) 2007-04-26 2013-09-11 武田薬品工業株式会社 二環性化合物およびその医薬用途
RU2479576C9 (ru) 2008-05-14 2014-03-10 Астеллас Фарма Инк. Амидное соединение
US8404736B2 (en) 2008-08-14 2013-03-26 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
CN102970869B (zh) * 2010-05-07 2014-07-16 葛兰素史密斯克莱有限责任公司 吲哚
EP2619182B1 (en) 2010-09-21 2016-11-09 Eisai R&D Management Co., Ltd. Pharmaceutical composition
US8828987B2 (en) 2010-12-10 2014-09-09 Rottapharm Biotech S.R.L. Pyridine amide derivatives as EP4 receptor antagonists
BR112014000087B1 (pt) 2011-07-04 2021-08-17 Rottapharm Biotech S.R.L. Derivados de amina cíclica como antagonistas do receptor ep4
ES2564353T3 (es) 2011-07-04 2016-03-22 Rottapharm Biotech S.R.L. Derivados de aminas cíclicas como agonistas de los receptores EP4
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
BR112015030315B1 (pt) * 2013-06-12 2022-10-04 Kaken Pharmaceutical Co., Ltd Derivado de 4-alquinilimidazol e produto farmacêutico que o compreende e antagonista de receptor de ep4
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
HUE057799T2 (hu) 2016-07-07 2022-06-28 Ono Pharmaceutical Co EP4 antagonistát és immunellenõrzõpont gátlót tartalmazó kombináció
WO2018162562A1 (en) 2017-03-10 2018-09-13 Bayer Pharma Aktiengesellschaft Use of an ep4 antagonist for the treatment of inflammatory pain
IL270021B (en) 2017-04-18 2022-08-01 Tempest Therapeutics Inc Bicyclic compounds and their use in the treatment of cancer
US11066405B2 (en) * 2017-04-18 2021-07-20 Tempest Therapeutics, Inc. Bicyclic compounds and their use in the treatment of cancer
SG11201908660RA (en) 2017-05-18 2019-10-30 Idorsia Pharmaceuticals Ltd N-substituted indole derivatives
JP7253500B2 (ja) 2017-05-18 2023-04-06 イドーシア ファーマシューティカルズ リミテッド ピリミジン誘導体
PL3625228T3 (pl) 2017-05-18 2021-12-20 Idorsia Pharmaceuticals Ltd Pochodne pirymidyny jako modulatory receptora pge2
AR111807A1 (es) 2017-05-18 2019-08-21 Idorsia Pharmaceuticals Ltd Derivados de benzofurano y benzotiofeno como moduladores del receptor pge2
IL270623B2 (en) 2017-05-18 2023-03-01 Idorsia Pharmaceuticals Ltd History of phenyl 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
KR20230170801A (ko) 2018-03-02 2023-12-19 셴젠 이오노바 라이프 사이언스 시오., 엘티디. 헤테로비시클릭 카르복시산들 및 그의 염들
DK3781550T3 (da) 2018-04-17 2025-01-27 Tempest Therapeutics Inc Bicykliske carboxamider og fremgangsmåder til anvendelse deraf
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
CA3126484A1 (en) * 2019-01-22 2020-07-30 Keythera (Suzhou) Pharmaceuticals Co. Ltd. Compound for inhibiting pge2/ep4 signaling transduction inhibiting, preparation method therefor, and medical uses thereof
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
US20230390303A1 (en) 2020-11-13 2023-12-07 Ono Pharmaceutical Co., Ltd. Cancer treatment by combination of ep4 antagonist and immune checkpoint inhibitor
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
JP2024532601A (ja) * 2021-08-27 2024-09-05 キーセラ（スーチョウ）バイオ－ファーマスーティカルズ カンパニー，リミテッド インドール化合物の固体形態、その調製方法及びその使用

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JP4292742B2 (ja) 2000-03-09 2009-07-08 小野薬品工業株式会社 インドール誘導体、その製造方法および用途
EP1267867B1 (en) * 2000-03-24 2008-05-14 Asterand Uk Limited Use of prostanoid ep4 receptor antagonists for the treatment of headache and assays for such antagonists
AU2001277056B2 (en) 2000-07-25 2005-09-29 Merck & Co., Inc. N-substituted indoles useful in the treatment of diabetes
MXPA06002551A (es) * 2003-09-03 2006-06-20 Pfizer Compuestos de aril o heteroaril amida.
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
US7968578B2 (en) * 2006-04-24 2011-06-28 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
ES2400293T3 (es) 2013-04-08
JP2010519260A (ja) 2010-06-03
WO2008104055A1 (en) 2008-09-04
EP2114877A1 (en) 2009-11-11
CN101622230A (zh) 2010-01-06
JP5301469B2 (ja) 2013-09-25
EP2114877A4 (en) 2010-10-27
EP2114877B1 (en) 2012-12-26
CA2679175A1 (en) 2008-09-04
CN101622230B (zh) 2012-08-22
AU2008221194A1 (en) 2008-09-04
AU2008221194B2 (en) 2013-06-27
US20090318518A1 (en) 2009-12-24
US8158671B2 (en) 2012-04-17

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Effective date: 20130208

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