CVT-4325: a potent fatty acid oxidation inhibitor with favorable oral bioavailability

Ken S. Rehder; E Elzein; P Ibrahim; DO Koltun; Ken S. Rehder; KD Shenk; TA Marquart; B Jiang; Yan Li; R Natero; M Nguyen; S Kerwar; N Chu; D Soohoo; J Hao; VY Maydanik; DA Lustig; D Zeng; K Leung; JA Zablocki

CVT-4325: a potent fatty acid oxidation inhibitor with favorable oral bioavailability

Elzein, E., Ibrahim, P., Koltun, DO., Rehder, K., Shenk, KD., Marquart, TA., Jiang, B., Li, Y., Natero, R., Nguyen, M., Kerwar, S., Chu, N., Soohoo, D., Hao, J., Maydanik, VY., Lustig, DA., Zeng, D., Leung, K., & Zablocki, JA. (2004). CVT-4325: a potent fatty acid oxidation inhibitor with favorable oral bioavailability. Bioorganic and Medicinal Chemistry Letters, 14(24), 6017-6021. https://doi.org/10.1016/j.bmcl.2004.09.077

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Abstract

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).