Quinazoline derivatives as MC-I inhibitors: Evaluation of myocardial uptake using Positron Emission Tomography in rat and non-human primate.
Bioorganic & medicinal chemistry letters 2007 Jun 14; 17(17):4882-5
Purohit A A, Benetti R R, Hayes M M, Guaraldi M M, Kagan M M, Yalamanchilli P P,
Bristol-Myers Squibb Medical Imaging, 331 Treble Cove Road, N. Billerica, MA 01860, USA.
Several quinazoline derivatives were made as mitochondrial complex 1 inhibitors. Compound 4 showed an IC(50) of 11.3nM 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 muPET 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.