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Biphenyl-substituted oxazolidinones as cholesteryl ester transfer protein inhibitors: modifications of the oxazolidinone ring leading to the discovery of anacetrapib.

Authors
  • 1
  • And 4 more
  • 1 Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065, United States. [email protected] , (Jersey)
Type
Published Article
Journal
Journal of Medicinal Chemistry
1520-4804
Publisher
American Chemical Society
Publication Date
Volume
54
Issue
13
Pages
4880–4895
Identifiers
DOI: 10.1021/jm200484c
PMID: 21682257
Source
Medline
License
Unknown

Abstract

The development of the structure-activity studies leading to the discovery of anacetrapib is described. These studies focused on varying the substitution of the oxazolidinone ring of the 5-aryloxazolidinone system. Specifically, it was found that substitution of the 4-position with a methyl group with the cis-stereochemistry relative to the 5-aryl group afforded compounds with increased cholesteryl ester transfer protein (CETP) inhibition potency and a robust in vivo effect on increasing HDL-C levels in transgenic mice expressing cynomolgus monkey CETP.

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