Bioorganic & Medicinal Chemistry Letters 2004-12-20

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

Elfatih Elzein, Prabha Ibrahim, Dmitry O Koltun, Ken Rehder, Kevin D Shenk, Timothy A Marquart, Bob Jiang, Xiaofen Li, Reina Natero, Yuan Li, Marie Nguyen, Suresh Kerwar, Nancy Chu, Daniel Soohoo, Jia Hao, Victoria Y Maydanik, David A Lustig, Dewan Zeng, Kwan Leung, Jeff A Zablocki

Index: Bioorg. Med. Chem. Lett. 14 , 6017-6021, (2004)

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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%, t(1/2)=13.6h, dog).