2-Arylbenzoxazoles as CETP inhibitors: Substitution of the benzoxazole moiety

Cameron J Smith; Amjad Ali; Liya Chen; Milton L Hammond; Matt S Anderson; Ying Chen; Suzanne S Eveland; Qiu Guo; Sheryl A Hyland; Denise P Milot; Carl P Sparrow; Samuel D Wright; Peter J Sinclair

doi:10.1016/j.bmcl.2009.10.099

2-Arylbenzoxazoles as CETP inhibitors: Substitution of the benzoxazole moiety

Bioorg Med Chem Lett. 2010 Jan 1;20(1):346-9. doi: 10.1016/j.bmcl.2009.10.099. Epub 2009 Oct 29.

Authors

Cameron J Smith¹, Amjad Ali, Liya Chen, Milton L Hammond, Matt S Anderson, Ying Chen, Suzanne S Eveland, Qiu Guo, Sheryl A Hyland, Denise P Milot, Carl P Sparrow, Samuel D Wright, Peter J Sinclair

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Rahway NJ 07065, United States. cameron_smith@merck.com

PMID: 19914065
DOI: 10.1016/j.bmcl.2009.10.099

Abstract

A series of 2-arylbenzoxazole inhibitors of the cholesterol ester transfer protein (CETP) is described. Structure-activity studies focused on variation of the substitution of the benzoxazole moiety. Substitution at the 5- and 7-positions of the benzoxazole moiety was found to be beneficial for CETP inhibition. Compound 47 was found to be the most potent inhibitor in this series and inhibited CETP with an IC(50) of 28nM.

MeSH terms

Acetanilides / chemical synthesis
Acetanilides / chemistry*
Acetanilides / pharmacokinetics
Administration, Oral
Animals
Anticholesteremic Agents / chemical synthesis
Anticholesteremic Agents / chemistry*
Anticholesteremic Agents / pharmacokinetics
Benzoxazoles / chemical synthesis
Benzoxazoles / chemistry*
Benzoxazoles / pharmacokinetics
Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
Cholesterol Ester Transfer Proteins / metabolism
Mice
Structure-Activity Relationship

Substances

Acetanilides
Anticholesteremic Agents
Benzoxazoles
Cholesterol Ester Transfer Proteins