Bioorganic & Medicinal Chemistry Letters 2012-02-01

Design and synthesis of boronic acid inhibitors of endothelial lipase.

Daniel P O'Connell, Daniel F LeBlanc, Debra Cromley, Jeffrey Billheimer, Daniel J Rader, William W Bachovchin

Index: Bioorg. Med. Chem. Lett. 22 , 1397-401, (2012)

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Abstract

Endothelial lipase (EL) and lipoprotein lipase (LPL) are homologous lipases that act on plasma lipoproteins. EL is predominantly a phospholipase and appears to be a key regulator of plasma HDL-C. LPL is mainly a triglyceride lipase regulating (V)LDL levels. The existing biological data indicate that inhibitors selective for EL over LPL should have anti-atherogenic activity, mainly through increasing plasma HDL-C levels. We report here the synthesis of alkyl, aryl, or acyl-substituted phenylboronic acids that inhibit EL. Many of the inhibitors evaluated proved to be nearly equally potent against both EL and LPL, but several exhibited moderate to good selectivity for EL.Copyright © 2011 Elsevier Ltd. All rights reserved.