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
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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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    • 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)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (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)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (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)

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MX2009011511A (es) 2007-04-26 2009-11-12 Takeda Pharmaceutical Compuesto biciclico y uso farmaceutico del mismo.
WO2009139373A1 (ja) 2008-05-14 2009-11-19 アステラス製薬株式会社 アミド化合物
WO2010019796A1 (en) * 2008-08-14 2010-02-18 Chemietek, Llc Heterocyclic amide derivatives as ep4 receptor antagonists
EP2392323A4 (en) 2009-01-30 2012-09-26 Univ Kyoto INHIBITOR OF PROSTATE CANCER PROGRESSION AND METHOD OF INHIBITING PROGRESSION
WO2010121382A1 (en) * 2009-04-21 2010-10-28 Merck Frosst Canada Ltd. Process for making indole cyclopropyl amide derivatives
SG185431A1 (en) * 2010-05-07 2012-12-28 Glaxosmithkline Llc Indoles
PE20131343A1 (es) 2010-09-21 2013-11-18 Eisai Randd Man Co Ltd Derivados de acido benzoico
US8828987B2 (en) 2010-12-10 2014-09-09 Rottapharm Biotech S.R.L. Pyridine amide derivatives as EP4 receptor antagonists
US9120824B2 (en) 2011-07-04 2015-09-01 Rottapharm Biotech S.R.L. Cyclic amine derivatives as EP4 receptor agonists
EP2729445B1 (en) 2011-07-04 2015-10-21 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
SG11201510121RA (en) * 2013-06-12 2016-01-28 Kaken Pharma Co Ltd 4-alkynyl imidazole derivative and medicine comprising same as active ingredient
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
US10316040B2 (en) 2015-10-16 2019-06-11 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
KR102473601B1 (ko) 2016-07-07 2022-12-01 오노 야꾸힝 고교 가부시키가이샤 Ep4 길항약과 면역 체크 포인트 저해약을 포함하여 이루어진 조합
WO2018162562A1 (en) 2017-03-10 2018-09-13 Bayer Pharma Aktiengesellschaft Use of an ep4 antagonist for the treatment of inflammatory pain
AU2018255300B2 (en) 2017-04-18 2021-10-28 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
KR102632028B1 (ko) 2017-05-18 2024-01-31 이도르시아 파마슈티컬스 리미티드 Pge2 수용체 조절제로서의 페닐 유도체
EP3625223B1 (en) 2017-05-18 2021-08-11 Idorsia Pharmaceuticals Ltd Pyrimidine derivatives
TWI768043B (zh) 2017-05-18 2022-06-21 瑞士商愛杜西亞製藥有限公司 N-取代吲哚衍生物
WO2018210987A1 (en) 2017-05-18 2018-11-22 Idorsia Pharmaceuticals Ltd Benzofurane and benzothiophene derivatives as pge2 receptor modulators
PE20191811A1 (es) 2017-05-18 2019-12-26 Idorsia Pharmaceuticals Ltd Derivados de pirimidina como moduladores del receptor de pge2
WO2019038156A1 (en) 2017-08-22 2019-02-28 Bayer Pharma Aktiengesellschaft USE OF AN EP4 ANTAGONIST FOR THE TREATMENT OF ARTHRITIS
AU2019229130B2 (en) * 2018-03-02 2021-11-25 Foshan Ionova Biotherapeutics Co., Inc. Heterobicyclic carboxylic acids and salts thereof
ES3010282T3 (en) 2018-04-17 2025-04-02 Tempest Therapeutics Inc Bicyclic carboxamides and methods of use thereof
CN112638871B (zh) * 2018-07-12 2024-08-30 罗达制药生物技术有限责任公司 作为ep4受体拮抗剂的(r)-4-(1-(1-(4-(三氟甲基)苄基)吡咯烷-2-甲酰胺)环丙基)苯甲酸
ES2995259T3 (en) 2019-01-22 2025-02-10 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
CN117940403A (zh) * 2021-08-27 2024-04-26 凯复(苏州)生物医药有限公司 一种吲哚类化合物的固体形式及其制备方法和用途

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CN1179945C (zh) * 2000-03-09 2004-12-15 小野药品工业株式会社 吲哚衍生物、其制备方法及用途
DE60038902D1 (de) * 2000-03-24 2008-06-26 Asterand Uk Ltd Verwendung von prostanoid-ep4-rezeptor-antagonisten zur behandlung von kopfschmerzen und nachweisverfahren für solche antagonisten
ATE362468T1 (de) * 2000-07-25 2007-06-15 Merck & Co Inc N-substituierte indole mit anwendung in der behandlung von diabetes
WO2005021508A1 (en) * 2003-09-03 2005-03-10 Pfizer Inc. Phenyl or pyridyl amide compounds as prostaglandin e2 antagonists
CA2608214C (en) * 2005-05-19 2013-08-20 Merck Frosst Canada Ltd. Quinoline derivatives as ep4 antagonists
US7968578B2 (en) * 2006-04-24 2011-06-28 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
CA2679175A1 (en) 2008-09-04
AU2008221194A1 (en) 2008-09-04
WO2008104055A1 (en) 2008-09-04
CN101622230B (zh) 2012-08-22
JP5301469B2 (ja) 2013-09-25
US20090318518A1 (en) 2009-12-24
EP2114877B1 (en) 2012-12-26
ES2400293T3 (es) 2013-04-08
JP2010519260A (ja) 2010-06-03
EP2114877A1 (en) 2009-11-11
AU2008221194B2 (en) 2013-06-27
EP2114877A4 (en) 2010-10-27
US8158671B2 (en) 2012-04-17
CN101622230A (zh) 2010-01-06

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