2-Arylpyrimidines: Novel CRF-1 receptor antagonists

The design, synthesis and structure–activity relationship studies of a novel series of CRF-1 receptor antagonists, the 2-arylpyrimidines, are described. The effects of substitution on the aromatic ring and the pyrimidine core on CRF-1 receptor binding were investigated. A number of compounds with Ki values below 10 nM and lipophilicity in a minimally acceptable range for a CNS drug (cLog P < 5) were discovered.

Graphical abstractThe design, synthesis, and structure–activity relationship studies of a novel series of CRF-1 receptor antagonists, the 2-arylpyrimidines, are described. The effects of substitution on the aromatic ring and the pyrimidine core on CRF-1 receptor binding were investigated. A number of compounds with Ki values below 10 nM and lipophilicity in a minimally acceptable range for a CNS drug (cLog P < 5) were discovered.Figure optionsDownload full-size imageDownload as PowerPoint slide