Synthesis and structure–activity relationships of N3-pyridylpyrazinones as corticotropin-releasing factor-1 (CRF 1) receptor antagonists

Abstract

A series of N 3-pyridylpyrazinones was investigated as corticotropin-releasing factor-1 receptor antagonists. It was observed that the binding affinity of analogues containing a pyridyl group was influenced not only by the substitution pattern on the pyridyl group, but also by the p K a of the pyridyl nitrogen. Analogues containing a novel 6-(difluoromethoxy)-2,5-dimethylpyridin-3-amine group were among the most potent N 3-pyridylpyrazinones synthesized. The synthesis and SAR of N 3-pyridylpyrazinones is described herein.