Bioorganic & Medicinal Chemistry 2013-12-15

Discovery of XEN445: a potent and selective endothelial lipase inhibitor raises plasma HDL-cholesterol concentration in mice.

Shaoyi Sun, Richard Dean, Qi Jia, Alla Zenova, Jing Zhong, Celene Grayson, Clark Xie, Andrea Lindgren, Pritpaul Samra, Luis Sojo, Margaret van Heek, Linus Lin, David Percival, Jian-Min Fu, Michael D Winther, Zaihui Zhang

Index: Bioorg. Med. Chem. 21(24) , 7724-34, (2013)

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Abstract

Endothelial lipase (EL) activity has been implicated in HDL metabolism and in atherosclerotic plaque development; inhibitors are proposed to be efficacious in the treatment of dyslipidemia related cardiovascular disease. We describe here the discovery of a novel class of anthranilic acids EL inhibitors. XEN445 (compound 13) was identified as a potent and selective EL inhibitor, that showed good ADME and PK properties, and demonstrated in vivo efficacy in raising plasma HDLc concentrations in mice. Copyright © 2013 Elsevier Ltd. All rights reserved.