Quinazoline derivatives as MC-I inhibitors: evaluation of myocardial uptake using Positron Emission Tomography in rat and non-human primate.
Purohit A,
Benetti R,
Hayes M,
Guaraldi M,
Kagan M,
Yalamanchilli P,
Su F,
Azure M,
Mistry M,
Yu M,
Robinson S,
Dischino DD,
Casebier D.
Bristol-Myers Squibb Medical Imaging, N Billerica, MA 01860, USA. ajay.purohit@bms.com
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 microPET 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.
PMID: 17604167 [PubMed - indexed for MEDLINE]