(azetidin-1-ylalkyl)lactams as tachykinin antagonists

C - Chemistry – Metallurgy – 07 – D

Patent

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C07D 401/06 (2006.01) A61K 31/395 (2006.01) C07D 207/263 (2006.01) C07D 211/76 (2006.01) C07D 223/10 (2006.01) C07D 401/14 (2006.01) C07D 403/06 (2006.01) C07D 403/14 (2006.01) C07D 405/14 (2006.01) C07D 409/14 (2006.01) C07D 413/14 (2006.01) C07D 417/14 (2006.01) C07D 451/02 (2006.01) C07D 521/00 (2006.01)

Patent

CA 2197086

The present invention provides compounds of formula (I) and the pharmaceutically acceptable salts thereof, wherein R is C3-C7 cycloalkyl, aryl or C1-C6 alkyl, said C1-C6 alkyl being optionally substituted by fluoro, - COOH, -COO(C1-C4 alkyl), C3-C7 cycloalkyl, adamantyl, aryl or het1, and said C3-C7 cycloalkyl being optionally substituted by 1 or 2 substituents each independently selected from C1-C4 alkyl, C3-C7 cycloalkyl, C1-C4 alkoxy, hydroxy, fluoro, fluoro(C1-C4)alkyl and fluoro(C1-C4)alkoxy; R1 is phenyl, naphthyl, thienyl, benzothienyl or indolyl, each optionally substituted by 1 or 2 substituents each independently selected from C1-C4 alkyl, C1-C4 alkoxy, halo and trifluoromethyl; R2 is -CO2H, -CONR3R4, -CONR5(C3-C7 cycloalkyl), - NR5(C2-C5 alkanoyl), -NR3R4, -NR5CONR5R6, (C3-C7 cycloalkyl-C1-C4 alkyl)R5N-, (C3-C7 cycloalkyl-C1-C4 alkyl)2N-, -NR5COCF3, -NR5SO2CF3, -NR5(SO2C1-C4 alkyl), -NR5SO2NR5R6, -NR5(SO2 aryl), -N(aryl) (SO2C1-C4 alkyl), -OR5, -O(C3- C7 cycloalkyl), -SO2NR5R6, het3 or a group of formulas: (a), (b), (c), (d), (e), (f), (g) or (h); X is C1-C4 alkylene; X1 is a direct link or C1-C6 alkylene; X2 is a direct link, CO, SO2 or NR5CO; and m is 0, 1 or 2; together with intermediates used in the preparation of compositions containing and the use as tachykinin antagonists of such derivatives.

La présente invention concerne des composés de la formule (I) et leurs sels pharmaceutiquement acceptables, formule dans laquelle R est cycloalkyle C¿3?-C¿7?, aryle ou alkyle C¿1?-C¿6?, ledit alkyle C¿1?-C¿6? étant éventuellement substitué par fluoro, -COOH, -COO(alkyle C¿1?-C¿4?), cycloalkyle C¿3?-C¿7?, adamantyle, aryle ou bien het?1¿, et ledit cycloalkyle C¿3?-C¿7? étant éventuellement substitué par un ou deux substituants choisis chacun indépendamment parmi alkyle C¿1?-C¿4?, cycloalkyle C¿3?-C¿7?, alcoxy C¿1?-C¿4?, hydroxy, fluoro, fluoro alkyle (C¿1?-C¿4?) et fluoro alcoxy (C¿1?-C¿4?); R?1¿ est phényle, naphtyle, thiényle, benzothiényle ou indolyle, chacun éventuellement substitué par un ou deux substituants choisis chacun indépendamment parmi alkyle C¿1?-C¿4?, alcoxy C¿1?-C¿4?, halo et trifluorométhyle; R?2¿ est -CO¿2?H, -CONR?3¿R?4¿, -CONR?5¿(cycloalkyle C¿3?-C¿7?), -NR?5¿(alcanoyle C¿2?-C¿5?), -NR?3¿R?4¿, -NR?5¿CONR?5¿R?6¿, (cycloalkyle C¿3?-C¿7?-alkyle C¿1?-C¿4?) R?5¿N-, (cycloalkyle C¿3?-C¿7?- alkyle C¿1?-C¿4?)¿2? N-, -NR?5¿COCS¿3?, -NR?5¿SO¿2?CS¿3?, -NR?5¿(SO¿2? alkyle C¿1?-C¿4?), -NR?5¿SO¿2?NR?5¿R?6¿, -NR?5¿(SO¿2? aryl), -N(aryle) (SO¿2? alkyle S¿1?-C¿4?), -OR?5¿, -O(cycloalkyle C¿3?-C¿7?), -SO¿2?NR?5¿R?6¿, het?3¿ ou bien un groupe de la formule (a), (b), (c), (d), (e), (f), (g) ou bien (h); X est alkylène C¿1?-C¿4?; X?1¿ est une liaison directe ou alkylène C¿1?-C¿6?; X?2¿ est une liaison directe, CO, SO¿2? ou bien NR?5¿CO; et m vaut 0, 1 ou 2. L'invention concerne également des intermédiaires utilisés dans la préparation de ces dérivés, des compositions les contenant et leur utilisation comme antagonistes de la tachykinine.

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