Affordable Access

deepdyve-link deepdyve-link
Publisher Website

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

Authors
  • Smith, Cameron J1
  • Ali, Amjad
  • Hammond, Milton L
  • Li, Hong
  • Lu, Zhijian
  • Napolitano, Joann
  • Taylor, Gayle E
  • Thompson, Christopher F
  • Anderson, Matt S
  • Chen, Ying
  • Eveland, Suzanne S
  • Guo, Qiu
  • Hyland, Sheryl A
  • Milot, Denise P
  • Sparrow, Carl P
  • Wright, Samuel D
  • Cumiskey, Anne-Marie
  • Latham, Melanie
  • Peterson, Laurence B
  • Rosa, Ray
  • 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
Publisher
American Chemical Society
Publication Date
Jul 14, 2011
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.

Report this publication

Statistics

Seen <100 times