Pyrido[2,3-d] pyrimidine derivatives and pharmaceutical...

C - Chemistry – Metallurgy – 07 – D

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C07D 471/04 (2006.01) A61K 31/505 (2006.01)

Patent

CA 2236683

Compounds represented by general formula (I) or pharmaceutically acceptable salts thereof which have the effect of inhibiting the activity of type IV phosphodiesterases and are usable as drugs, in particular, type IV phosphodiesterase inhibitors or preventives and remedies for diseases in association with the sthenic type IV phosphodiesterase activity, in particular, respiratory diseases such as bronchial asthma. In said formula (I), X represents oxygen or sulfur; R1 represents lower alkyl, cycloalkyl(lower alkyl) or cycloalkyl; R2 represents hydrogen, halogeno, lower alkyl, halo(lower alkyl), hydroxy(lower alkyl), mercapto(lower alkyl), (lower alkoxy)(lower alkyl), (lower alkylthio)(lower alkyl), (lower alkanoyloxy)(lower alkyl), (lower alkanoylthio)(lower alkyl), (lower alkanoyl)(lower alkyl), hydroxyimino(lower alkyl), (lower alkoxyimino)(lower alkyl), cycloalkyl, aryl or lower alkanoyl; R3 represents hydrogen, halogeno or lower alkyl; R4 represents hydrogen, or lower alkyl; R5 represents cycloalkyl optionally substituted by the same group as R6; naphthyl optionally substituted by the same group as R6; a 5- or 6-membered monocyclic heterocycle optionally substituted by the same group as R6, optionally fused with a benzene ring and having one to four heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur atoms; or a group of formula (a); and R6 represents halogeno, lower alkyl, halo(lower alkyl), hydroxy, lower alkoxy, cyano or nitro.

L'invention porte sur des composés de formule générale (I) et leurs sels pharmacocompatibles, utilisables en tant que médicaments et, possédant une action inhibitrice sur les activités des phosphodiestérases de type IV et servant en particulier à l'inhibition, à la prévention ou au traitement des maladies associées à l'activité de la phosphodiestérase sténique de type IV, et en particulier des troubles respiratoires tels que l'asthme bronchique. Dans la formule (I), X représente O ou S; R?1¿ représente alkyle inférieur, cycloalkyl (alkyle inférieur), ou cycloalkyle; R?2¿ représente H, halogéno, alkyle inférieur, halo(alkyle inférieur), hydroxy(alkyle inférieur), mercapto(alkyle inférieur), (alcoxy inférieur)(alkyle inférieur), (alkylthio inférieur)(alkyle inférieur), (alcanoyloxy inférieur)(alkyle inférieur), (alcanoylthio inférieur)(alkyle inférieur), (alcanoyle inférieur)(alkyle inférieur), (hydroxyimino)(alkyle inférieur), (alcoxyimino inférieur)(alkyle inférieur), cycloalkyle, aryle, ou alcanoyle inférieur; R?3¿ représente H, halogéno ou alkyle inférieur; R¿4? représente H ou alkyle inférieur; R?5¿ représente cycloalkyle facultativement substitué par le même groupe que R?6¿; naphtyle facultativement substitué par le même groupe que R?6¿, un hétérocycle monocyclique à 5 ou 6 éléments facultativement substitué par le même groupe que R?6¿ et facultativement fusionné avec un noyau benzénique et comportant de un à quatre hétéroatomes sélectionnés parmi des atomes de N, O ou S; ou un groupe de formule (a); et R?6¿ représente halogéno, alkyle inférieur, halo(alkyle inférieur), hydroxy, alcoxy inférieur, cyano ou nitro.

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