CVT-4325: a potent fatty acid oxidation inhibitor with favorable oral bioavailability
Elzein, E., Ibrahim, P., Koltun, D. O., Rehder, K., Shenk, K. D., Marquart, T. A., ... Zablocki, J. A. (2004). CVT-4325: a potent fatty acid oxidation inhibitor with favorable oral bioavailability. Bioorganic and Medicinal Chemistry Letters, 14(24), 6017-6021. DOI: 10.1016/j.bmcl.2004.09.077
New inhibitors of palmitoyl-CoA oxidation are based on the introduction of nitrogen heterocycles in the ‘Western Portion’ of the molecule. SAR studies led to the discovery of CVT-4325 (shown), a potent FOXi (IC50 = 380 nM rat mitochondria) with favorable PK properties (F = 93%, t1/2 = 13.6 h, dog).