Carbamates derived from arylalkylamines

C - Chemistry – Metallurgy – 07 – D

Patent

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Details

C07D 453/02 (2006.01) A61K 31/439 (2006.01)

Patent

CA 2414514

The invention relates to carbamates having general structure (I), wherein: R1, R2 and R3 are H, OH, SH, CN, F, CI, Br, I, (C1-C4)-alkylthio, (C1-C4)-alkoxyl, (C1-C4)-alkoxyl substituted by one or several F radicals, carbamoylamine, (C1- C4)-alkyl and (C1-C4)-alkyl substituted by one or several F or OH radicals; R4 represents a substituted or non-substituted cycloalkyl or cycloaryl radical (a heteroalkyl radical or not). The amine of the quinuclidine ring can also be forming quaternary ammonium salts or in an oxidized state (N-oxide). Carbamates (I) are antagonists of the M3 muscarinic receptor, and selectively, the M2 receptor. Hence, they can be used in the treatment of uri nary incontinence (particularly due to bladder instability), irritable bowel syndrome, diseases of the respiratory tract (particularly chronic obstructive pulmonary disease, chronic bronchitis, asthma, emphysema and rhinitis) and in ophthalmologic operations.

L'invention concerne des carbamates représentés par la formule générale (I), dans laquelle R1, R2 et R3 sont H, OH, SH, CN, F, CI, Br, I, alkyltio (C¿1?-C¿4?), alcoxyle (C¿1?-C¿4?), alcoxyle (C¿1?-C¿4?) substitué par un ou plusieurs radicaux F, carbamylamine, alkyle (C¿1?-¿4?) et alkyle (C¿1?-C¿4?) substitué par un ou plusieurs radicaux F ou OH; R4 est un radical cycloalkylique ou arylique (hétéroarylique ou pas), avec ou sans substitution. L'amine de l'anneau de quinuclidine peut, de plus, former des sels d'ammonium quaternaire, ou se trouver dans un état oxydé (N-oxyde). Les carbamates (I) sont des antagonistes du récepteur muscarinique M¿3?, de manière sélective face au récepteur M¿2?, et peuvent ainsi être utilisés dans le traitement de l'incontinence urinaire (en particulier celle associée à l'instabilité vésicale), dans le traitement du syndrome du côlon irritable, et dans le traitement des maladies des voies respiratoires (en particulier la bronchopneumopathie chronique obstructive, la bronchite chronique, l'asthme, l'emphysème et la rhinite), ainsi que dans les interventions ophtalmiques.

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