Synthesis and evaluation of carbamate and aryl ether substituted pyrazinones as corticotropin releasing factor-1 (CRF1) receptor antagonists.

A series of pyrazinone-based compounds incorporating either carbamate or aryl ether groups was synthesized and evaluated as corticotropin-releasing factor-1 (CRF1) receptor antagonists. Structure–activity relationship studies led to the identification of highly potent CRF1 receptor antagonists 14a (IC50=0.74nM) and 14b (IC50=1.9nM). The synthesis, structure–activity relationships and in vitro metabolic stability properties of compounds in this series will be described.