Design and synthesis of boronic acid inhibitors of endothelial lipase.
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.
Tufts University School of Medicine, Department of Biochemistry, 136 Harrison Ave., Boston, MA 02111, United States.
Daniel P
DP
O'Connell
Daniel F
DF
LeBlanc
Debra
D
Cromley
Jeffrey
J
Billheimer
Daniel J
DJ
Rader
William W
WW
Bachovchin
D001897:Boronic Acids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D004727:Endothelium / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D020128:Inhibitory Concentration 50; D008049:Lipase / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D019308:Palmitic Acid / Q000737:chemistry
D001897:Boronic Acids; D019308:Palmitic Acid; D008049:Lipase