1,3,8-trisubstituted-1,3,8-triaza-spiro[4.5]decan-4-one derivatives as ligands of the ORL-1 receptor

摘要

The present invention is directed to novel 1,3,8-trisubstituted-1,3,8-triaza-spiro[4.5]decan-4-one derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions mediated by the ORL-1 G-protein coupled receptor.

主权项

1. A compound of formula (I) wherein R1 is 1-acenaphthenyl; R2 is 4-fluorophenyl; A1 is selected from the group consisting of —CH2—, —CH2CH2—, —CH2CH2CH2— and —CH2CH2CH2CH2—; R3 is selected from the group consisting of wherein R4 is selected from the group consisting of hydroxy, cycloalkyl, phenyl, benzyl, imidazolyl, pyridyl, —C1-4alkyl-NRARB, —C1-4alkyl-OH, —C1-4alkyl-O—C1-4alkyl, —C(O)OH and —C(O)O—C1-4alkyl; wherein the phenyl, imidazolyl or pyridyl, is optionally substituted with one or more substituents independently selected from the group consisting of halogen and C1-4alkyl; wherein RA and RB are each independently selected from the group consisting of hydrogen and C1-4alkyl; and wherein R5 is selected from the group consisting of hydroxy, cycloalkyl, phenyl, benzyl, imidazolyl, pyridyl, —C1-4alkyl-NRCRD, —C1-4alkyl-OH, —C1-4alkyl-O—C1-4alkyl, —C(O)OH and —C(O)O—C1-4alkyl; wherein the phenyl, imidazolyl or pyridyl, is optionally substituted with one or more substituents independently selected from the group consisting of halogen and C1-4alkyl; and wherein RC and RD are each independently selected from the group consisting of hydrogen and C1-4alkyl; or a pharmaceutically acceptable salt thereof.