N-2 ADAMANTANYL-2-PHENOXY-ACETAMIDE DERIVATIVES AS 11-BETA HYDROXYSTEROID DEHYDROGENASE INHIBITORS

摘要

The N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n is 1, 2, 3, or 4; Z represents O, S, NR⁶, SO or SO₂; R¹ represent hydrogen, cyano, hydroxy, or C_1-4alkyl optionally substituted with halo, R² represents hydrogen, C_1-4alkyl, or C_1-4alkyloxy-; R³ represents hydrogen, C_1-4alkyl, C_1-4alkyloxy- or R³ combined with R² form together a divalent radical selected from the group consisting of -O-CH₂- (a), -NR⁷-CH₂- (b), -(CR⁸R⁹)_m- (c) and -CR¹⁰= (d) wherein m represents 1 or 2 and R⁷, R⁸, R⁹ and R¹⁰ are each independently selected from hydrogen or C_1-4alkyl; R⁴ represents hydrogen, halo, hydroxy, cyano, amino, NR¹¹R¹², C_1-4alkyloxy- optionally substituted with one or where possible two or three substituents selected from hydroxy and halo or R⁴ represents C_1-4alkyl optionally substituted with one or where possible two or three substituents selected from hydroxy and halo; R⁵ represents hydrogen, halo, cyano, amino, phenyl, hydroxy, C_1-4alkyloxycarbonyl, hydroxycarbonyl, NR¹³R¹⁴ or C_1-4alkyl substituted with one or more substituents selected from hydroxycarbonyl, phenyl, C_1-4alkyloxy or NR¹⁵R¹⁶; R⁶ represents hydrogen; R¹¹ and R¹² each independently represent hydrogen, C_1-4 alkyl or C_1-4 alkylcarbonyl-; R¹³ and R¹⁴ each independently represent hydrogen, C_1-4 alkyl or C_1-4 alkylcarbonyl-; R¹⁵ and R¹⁶ each independently represent hydrogen, C_1-4 alkyl or C_1-4 alkylcarbonyl-; R¹⁷ and R¹⁸ each independently represent hydrogen, C_1-4 alkyl or C_1-4 alkylcarbonyl-.