Synthesis and structure–activity relationships of N3-pyridylpyrazinones as corticotropin-releasing factor-1 (CRF1) receptor antagonists

A series of N3-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 pKa of the pyridyl nitrogen. Analogues containing a novel 6-(difluoromethoxy)-2,5-dimethylpyridin-3-amine group were among the most potent N3-pyridylpyrazinones synthesized. The synthesis and SAR of N3-pyridylpyrazinones is described herein.

Graphical abstractThe structure–activity relationships of a series of N3-pyridylpyrazinones as corticotropin-releasing factor-1 receptor antagonists was investigated.Figure optionsDownload full-size imageDownload as PowerPoint slide