Quinazoline derivatives as MC-I inhibitors: evaluation of myocardial uptake using Positron Emission Tomography in rat and non-human primate.

Abstract Several quinazoline derivatives were made as mitochondrial complex 1 inhibitors. Compound 4 showed an IC 50 of 11.3 nM and was the most potent compound of this series. The 18 F analog of 4 , [ 18 F] 4 , was injected in the rat and showed high and rapid heart uptake, fast liver clearance, and low blood uptake. Images obtained using a μPET showed clear delineation of the myocardium in normal rats and perfusion deficit in ischemic rats. In the non-human primate, [ 18 F] 4 showed rapid uptake and clearance from the myocardium and high liver uptake.