Diabetes Research Today is a free monthly online journal that collates and summarizes the latest research about Diabetes, including details on insulin, type i, type ii, diet, treatment, prevention.

Influence of various central moieties on the hypolipidemic properties of long hydrocarbon chain diols and diacids.

Oniciu DC, Dasseux JL, Yang J, Mueller R, Pop E, Denysenko A, Duan C, Huang TB, Zhang L, Krause BR, Drake SL, Lalwani N, Cramer CT, Goetz B, Pape ME, McKee A, Fici GJ, Lutostanski JM, Brown SC, Bisgaier CL

Esperion Therapeutics, A Division of Pfizer Global Research and Development, 3621 South State Street, 695 KMS Place, Ann Arbor, Michigan 48108, USA. oniciu@yahoo.com

A series of long (11-15) hydrocarbon chain diols and diacids with various central functional groups and terminal gem-dimethyl or -methyl/aryl substituents was synthesized and evaluated in both in vivo and in vitro assays for its potential to favorably alter lipid disorders including metabolic syndrome. Compounds were assessed for their effects on the de novo incorporation of radiolabeled acetate into lipids in primary cultures of rat hepatocytes, as well as for their effects on lipid and glycemic variables in obese female Zucker fatty rats, Crl:(ZUC)-faBR. The most active compounds were hydroxyl-substituted symmetrical diacids and diols with a 13-atom chain and terminal gem-dimethyl substituents. Furthermore, biological activity was enhanced by central substitution with O, C=O, S, S=O compared to the methylene analogues and was diminished for compounds with central functional groups such as carbamate, ester, urea, acetylmethylene, and hydroxymethylene.

Published 5 January 2006 in J Med Chem, 49(1): 334-48.
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