| Literature DB >> 18063367 |
Jeffrey A Pfefferkorn1, Scott D Larsen, Chad Van Huis, Roderick Sorenson, Tom Barton, Thomas Winters, Bruce Auerbach, Chenyan Wu, Thaddeus J Wolfram, Hongliang Cai, Kathleen Welch, Nadia Esmaiel, JoAnn Davis, Richard Bousley, Karl Olsen, Sandra Bak Mueller, Thomas Mertz.
Abstract
Cholesterol absorption inhibition (CAI) represents an important treatment option for hypercholesterolemia. Herein, we report the design and evaluation of a series of substituted oxazolidinones as ligands for the Niemann Pick C1 Like 1 (NPC1L1) protein, a key mediator of cholesterol transport. Novel analogs were initially evaluated in a brush border membrane NPC1L1 binding assay; subsequently, promising compounds were evaluated in vivo for acute inhibition of cholesterol absorption. These studies identified analogs with low micromolar NPC1L1 binding affinity and acute in vivo efficacy of >50% absorption inhibition at 3mg/kg.Entities:
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Year: 2007 PMID： 18063367 DOI： 10.1016/j.bmcl.2007.11.083
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823