CA2393749C - Inhibiteurs de 8-arylquinoline phosphodiesterase-4 substituee - Google Patents

Inhibiteurs de 8-arylquinoline phosphodiesterase-4 substituee Download PDF

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Publication number
CA2393749C
CA2393749C CA002393749A CA2393749A CA2393749C CA 2393749 C CA2393749 C CA 2393749C CA 002393749 A CA002393749 A CA 002393749A CA 2393749 A CA2393749 A CA 2393749A CA 2393749 C CA2393749 C CA 2393749C
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c6alkyl
phenyl
methylsulfonyl
aryl
alkyl
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Expired - Fee Related
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CA2393749A1 (fr
Inventor
Denis Deschenes
Daniel Dube
Michel Gallant
Yves Girard
Patrick Lacombe
Dwight Macdonald
Anthony Mastracchio
Helene Perrier
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Merck Canada Inc
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Merck Frosst Canada Ltd
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    • C07—ORGANIC CHEMISTRY
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    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • A—HUMAN NECESSITIES
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    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
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    • A—HUMAN NECESSITIES
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D215/14—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

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  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Quinoline Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne de nouvelles 8-arylquinolines substituées représentées par la formule (I) ou un sel pharmaceutiquement acceptable de ces dernières. Dans la formule (I), S1, S2 et S3 représentent indépendamment H, -OH, halogène, -C1-C6alkyle, -NO2, -CN, ou -C1-C6alcoxy, les groupes alkyle et alcoxy étant facultativement substitués par 1 à 5 substituants; chaque substituant étant lui-même un halogène ou OH; R1 représente H, OH, halogène, carbonyle, ou -C1-C6alkyle, -cycloC3-C6alkyle, -C1-C6alcényle, -C1-C6alcoxy, aryle, hétéroaryle, -CN, -hétérocycloC3-C6alkyle, -amino, -C1-C6alkylalmino, -(C1-C6alkyle)(C1-C6alkyle)amino, -C1-C6alkyl(oxy)C1-C6alkyle, -C(O)NH(aryle), -C(O)NH(hétéroaryle), -SOnNH(aryle), -SOnNH(hétéroaryle), -SOnNH(C1-C6alkyle), -C(O)N(C0-C6alkyle), (CO-C6alkyle),-NH-SOn-(C1-C6alkyle), -SOn-(C1-C6alkyle), -(C1-C6alkyle)-O-C(CN)-dialkylamino, ou un groupe -(C1-C6alkyl)-SOn-(C1-C6alkyle), chaque groupe pouvant être facultativement substitué par 1 à 5 susbtituants; chaque substituant représentant indépendamment halogène, -OH, -CN, -C1-C6alkyle, -cycloC3-C6alkyle, -C(O)(hétérocycloC3-C6alkyle), -C(O)-O-(C0-C6alkyle), -C(O)-aryloxy, -C1-C6alcoxy, -(C0-C6alkyle)(C0-C6alkyle)amino, cycloalkyloxy, acyle, acyloxy, -cycloC3-C6alkyle, hétérocycloC3-C6alkyle, aryle, hétéroaryle, carbonyle, carbamoyle, ou -SOn-(C1-C6alkyle); A représente CH, C-ester, ou C-R4; R2 et R3 représentent indépendamment aryle, hétéroaryle, H, halogène, -CN, -C1-C6alkyle, hétérocycloC3-C6alkyle, -C1-C6alcoxy, carbonyle, carbamoyle, -C(O)OH, -C1-C6alkyle)-SOn-(C1-C6alkyle), -C(O)N(C0-C6alkyle)(C0-C6alkyle), ou un groupe -C1-C6alkylacylamino, chaque groupe étant facultativement substitué par 1 à 5 substituants et chaque substituant étant indépendamment aryle, hétéroaryle, halogène, -NO2, -C(O)OH, carbonyle, -CN, -C1-C6alkyle, -SOn-(C1-C6alkyle), -SOn-(aryle), aryloxy, -hétéroaryloxy, C1-C6alcoxy, N-oxyde, -C(O)-hétérocycloC3-C6alkyle, -NH-cycloC3-C6alkyle, amino, -OH, ou -(C0-C6alkyle)(C0-C6alkyle)amino, groupe substituant -C(O)-N(C0-C6alkyle)(C0-C6alkyle), chaque groupe substituant étant facultativement substitué par -OH, C1-C6alcoxy, -C1-C6alkyle, -cycloC3-C6alkyle, aryloxy, -C(O)OH, -C(O)O(C1-C6alkyle), halogène, -NO2, -CN, -SOn-(C1-C6alkyle), ou -C(O)-N(C0-C6alkyle)(C0-C6alkyle); R2 ou R3 doit obligatoirement représenter aryle ou hétéroaryle, facultativement substitué; lorsque R2 et R3 représentent tous les deux aryle ou hétéroaryle, alors R2 et R3 peuvent être facultativement reliés par un pont thio, oxy, ou (C1-C4alkyle) pour former un système à trois cycles fusionnés. Ces composés sont des inhibiteurs de PDE4.
CA002393749A 1999-12-22 2000-12-20 Inhibiteurs de 8-arylquinoline phosphodiesterase-4 substituee Expired - Fee Related CA2393749C (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US17152299P 1999-12-22 1999-12-22
US60/171,522 1999-12-22
PCT/CA2000/001559 WO2001046151A1 (fr) 1999-12-22 2000-12-20 Inhibiteurs de 8-arylquinoline phosphodiesterase-4 substituee

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CA2393749A1 CA2393749A1 (fr) 2001-06-28
CA2393749C true CA2393749C (fr) 2008-06-17

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CA002393749A Expired - Fee Related CA2393749C (fr) 1999-12-22 2000-12-20 Inhibiteurs de 8-arylquinoline phosphodiesterase-4 substituee

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EP (1) EP1244628A1 (fr)
JP (1) JP3782011B2 (fr)
KR (1) KR20020082839A (fr)
CN (1) CN1221534C (fr)
AR (1) AR029214A1 (fr)
AU (1) AU778531B2 (fr)
BG (1) BG65403B1 (fr)
BR (1) BR0016651A (fr)
CA (1) CA2393749C (fr)
CO (1) CO5261613A1 (fr)
CZ (1) CZ20022171A3 (fr)
DZ (1) DZ3244A1 (fr)
EA (1) EA004747B1 (fr)
EE (1) EE200200342A (fr)
GE (1) GEP20053626B (fr)
HR (1) HRP20020545A2 (fr)
HU (1) HUP0203896A3 (fr)
IL (1) IL150114A0 (fr)
IS (1) IS6413A (fr)
MX (1) MXPA02006329A (fr)
MY (1) MY134008A (fr)
NO (1) NO20023013L (fr)
NZ (1) NZ520258A (fr)
PE (1) PE20010989A1 (fr)
PL (1) PL355752A1 (fr)
SK (1) SK8972002A3 (fr)
TW (1) TWI280240B (fr)
UA (1) UA74815C2 (fr)
WO (1) WO2001046151A1 (fr)
YU (1) YU47102A (fr)
ZA (1) ZA200204862B (fr)

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US7776315B2 (en) 2000-10-31 2010-08-17 Boehringer Ingelheim Pharma Gmbh & Co. Kg Pharmaceutical compositions based on anticholinergics and additional active ingredients
US6740666B2 (en) * 2000-12-20 2004-05-25 Merck & Co., Inc. Substituted 8-arylquinoline phosphodiesterase-4 inhibitors
HRP20030507A2 (en) * 2000-12-20 2005-06-30 Merck & Co. Inc. Process for making substituted 8-arylquinolinium benzensulfonate
WO2003002118A1 (fr) * 2001-06-27 2003-01-09 Merck Frosst Canada & Co. Arylquinones inhibiteurs de pde4 a substitution en position 8
WO2003010137A1 (fr) * 2001-07-24 2003-02-06 Merck & Co., Inc. Preparation de sulfonyl quinoleine
JP2005505570A (ja) * 2001-09-19 2005-02-24 アルタナ　ファルマ　アクチエンゲゼルシャフト Ｐｄｅ阻害剤及びロイコトリエン受容体拮抗物質の複合薬
EP1487797B1 (fr) 2002-03-18 2009-05-27 Merck Frosst Canada Ltd. 8-arylquinoleine substituee au moyen d'un pont hetero comme inhibiteurs de pde-4
JP2006519874A (ja) * 2003-03-05 2006-08-31 セルジーン・コーポレーション ジフェニルエチレン化合物およびその使用
WO2005091752A2 (fr) * 2004-03-25 2005-10-06 Synta Pharmaceuticals Corp. Derives d'acrylonitrile utilises dans le traitement ou la prevention des inflammations et des troubles immunitaires
CA2608158A1 (fr) * 2005-05-19 2006-11-23 Synergenz Bioscience Limited Methodes et compositions pour evaluation de la fonction et de troubles pulmonaires
ES2443342T3 (es) 2006-07-05 2014-02-19 Takeda Gmbh Combinación de inhibidor de la HMG-CoA reductasa rosuvastatina con un inhibidor de la fosfodiesterasa 4, tal como roflumilast, roflumilast-N-óxido para el tratamiento de enfermedades pulmonares inflamatorias
CA2657093A1 (fr) * 2006-07-07 2008-01-10 Steven P. Govek Inhibiteurs de pde4 a base de composes d'heteroaryle bicyclique
EP2076288A2 (fr) * 2006-09-22 2009-07-08 Braincells, Inc. Combinaison comprenant un inhibiteur de la hmg-coa réductase et un deuxième agent neurogène pour le traitement d'une maladie du system nerveux central et pour augmenter la neurogenèse
CA2676715A1 (fr) 2007-02-12 2008-08-21 Merck & Co., Inc. Derives de piperazine pour le traitement de la maladie d'alzheimer et des conditions apparentees
EP2291181B9 (fr) 2008-04-18 2013-09-11 University College Dublin National University Of Ireland, Dublin Utilisation de la captodiamine pour le traitement des symptômes de la dépression
JP6023926B2 (ja) 2010-02-12 2016-11-09 株式会社ＡｓｋＡｔ 認知症治療のための５−ｈｔ４受容体アゴニスト
WO2013024022A1 (fr) 2011-08-12 2013-02-21 INSERM (Institut National de la Santé et de la Recherche Médicale) Méthodes et compositions pharmaceutiques pour traiter l'hypertension pulmonaire
US20140328893A1 (en) 2011-10-11 2014-11-06 Institut National De La Sante Et De La Recherche Medicale (Inserm) Nutlin compounds for use in the treatment of pulmonary hypertension
JP2020532551A (ja) * 2017-09-03 2020-11-12 アンジオン バイオメディカ コーポレーション Ｒｈｏ関連コイルドコイルキナーゼ（ＲＯＣＫ）阻害剤としてのビニルヘテロ環

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JPH11209350A (ja) * 1998-01-26 1999-08-03 Eisai Co Ltd 含窒素複素環誘導体およびその医薬

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