The original benzoxazole scaffold-redesign paper discovers CETP inhibitor 11v, raising HDL cholesterol by 24 mg/dl in mice (Bioorg Med Chem Lett 2011)

Original title: 2-(4-carbonylphenyl)benzoxazole inhibitors of CETP: scaffold design and advancement in HDLc-raising efficacy

Bioorg Med Chem Lett · 25 November 2010 · 6

Sweis RF, Hunt JA, Kallashi F, Hammond ML, Chen Y, Eveland SS, Guo Q, Hyland SA, Milot DP, Cumiskey AM, Latham M, Rosa R et al.

In developing 2-phenylbenzoxazoles as inhibitors of cholesteryl ester transfer protein (CETP), initial efforts engineered replacements for the aniline substructure of the benchmark molecule. Reversing the connectivity of the central aniline produced a new class of 2-(4-carbonylphenyl)benzoxazoles. Structure-activity studies at the C-7 position and the terminal pyridine ring optimized potency and HDL-cholesterol-raising efficacy within this new class, leading to the discovery of benzoxazole 11v, which raised HDL cholesterol by 24 mg/dl in a transgenic mouse pharmacodynamic model.

Original abstract

The development of 2-phenylbenzoxazoles as inhibitors of cholesteryl ester transfer protein (CETP) is described. Initial efforts aimed at engineering replacements for the aniline substructures in the benchmark molecule. Reversing the connectivity of the central aniline lead to a new class of 2-(4-carbonylphenyl)benzoxazoles. Structure-activity studies at the C-7 and terminal pyridine ring allowed for the optimization of potency and HDLc-raising efficacy in this new class of inhibitors. These efforts lead to the discovery of benzoxazole 11v, which raised HDLc by 24 mg/dl in our transgenic mouse PD model.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.