Studies on Quinazolines. 12.^1 Design of 4-Amino-8-arylquinazoline Derivatives as Potential Non-Peptide Corticotropin-Releasing Hormone Receptor I (CRHR1) Antagonists

Abstract

Four 8-aryl-4-(N-cyclopropylmethyl-N-propyl)amino-2-methylquinazolines were synthesized, and their binding affinity for corticotropin-releasing hormone type 1 receptor (CRHR1) was investigated. Compounds 22 and 23 possessed high rCRHR1 affinities of K(subscript i)=13 and 50 nM, respectively. The quinazoline derivatives showed parallel SAR to the other known bicyclic system; the ortho-substituent on the 8-aryl ring is indispensable.