Discovery and structure-activity relationships of a novel class of quinazoline glucokinase activators.

Abstract We describe design, syntheses and structure–activity relationships of a novel class of 4,6-disubstituted quinazoline glucokinase activators. Prototype quinazoline leads ( 4 and 5 ) were designed based on the X-ray analyses of the previous 2-aminobenzamide lead classes. Modifications of the quinazoline leads led to the identification of a potent GK activator ( 21d ).