Heterocyclic compounds as inhibitors of rotamase enzymes

Details Heterocyclic compounds as inhibitors of rotamase enzymes Heterocyclic compounds as inhibitors of rotamase enzymes

C - Chemistry, Metallurgy

07

D

C07D 413/14 (2006.01) A61K 31/44 (2006.01) C07D 221/00 (2006.01) C07D 235/00 (2006.01) C07D 235/24 (2006.01) C07D 401/04 (2006.01) C07D 401/14 (2006.01) C07D 413/04 (2006.01) C07D 417/04 (2006.01) C07D 417/14 (2006.01) C07D 471/04 (2006.01) C07D 521/00 (2006.01)

Patent

CA 2338214

Compounds of the formula (I) wherein A is unbranched C3-C5 alkylene optionally substituted by C1-C6 alkyl; X is O, S, NH or N(C1-C6 alkyl); Y is O, S, NH or N(C1-C6 alkyl); R is a C-linked, 4- to 6- membered ring, non-aromatic, heterocyclic group containing one nitrogen heteroatom, said group being optionally substituted by 1, 2 or 3 substituent(s) each independently selected from C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, aryl, het, -CO2(C1-C6 alkyl), -CO(het), - CONR5R6 and -CO(aryl), said alkyl and alkenyl being optionally substituted by 1 or 2 substituent(s) each independently selected from C3-C7 cycloalkyl, aryl, het, -O(aryl), -O(C1-C2 alkylene) aryl, -CO(het), -CONR5R6 and -CO(aryl); are inhibitors of rotamase enzymes in particular FKBP-12 and FKBP-52. The compounds therefore moderate neuronal regeneration and outgrowth and can be used for treating neurological disorders arising from neurodegenerative diseases or other disorders involving nerve damage.

L'invention concerne les composés de la formule (I) dans laquelle A représente alkylène C3-C5 non ramifié facultativement substitué par alkyle C1-C6; X représente O, S, NH ou N(alkyle C1-C6); Y représente O, S, NH ou N (alkyle C1-C6); R représente un cycle à liaison C, de 4 à 6 éléments, un groupe non aromatique hétérocyclique contenant un hétéro-atome d'azote, ledit groupe étant facultativement substitué par 1, 2 ou 3 substituants choisis chacun indépendamment parmi alkyle C1-C6, alcényle C2-C6, cycloalkyle C3-C7, aryle, het, -CO2(alkyle C1-C6), -CO(het), -CONR5R6 et -CO(aryle), ledit alkyle et ledit alcényle étant facultativement substitués par 1 ou 2 substituants choisis chacun indépendamment parmi cycloalkyle C3-C7, aryle, het, -O(aryle), -O(alkyle C1-C2) aryle, -CO(het), -CONR5R6 et -CO(aryle); lesquels composés sont des inhibiteurs des enzymes rotamase notamment FKBP-12 et FKBP-52. Les composés modèrent par conséquent la régénération et l'excroissance neuronales, ils peuvent être utilisés dans le traitement de troubles neurologiques ayant pour origine des maladies neurodégénératives ou d'autres troubles impliquant des lésions nerveuses.

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