Synthesis and optimization of novel 4,4-disubstituted cyclohexylbenzamide derivatives as potent 11ß-HSD1 inhibitors.

ABSTRACT

The synthesis and SAR of a series of 4,4-disubstituted cyclohexylbenzamide inhibitors of 11ß-HSD1 are described. Optimization rapidly led to potent, highly selective, and orally bioavailable inhibitors demonstrating efficacy in both rat and non-human primate ex vivo pharmacodynamic models.