SAR study on the central phenyl ring of biphenyl oxazolidinone CETP inhibitors finds analogs matching anacetrapib in potency (Bioorg Med Chem Lett 2012)

Original title: SAR studies on the central phenyl ring of substituted biphenyl oxazolidinone-potent CETP inhibitors

Bioorg Med Chem Lett · 16 November 2011 · 3

Lu Z, Chen YH, Napolitano JB, Taylor G, Ali A, Hammond ML, Deng Q, Tan E, Tong X, Xu SS, Latham MJ, Peterson LB et al.

Using anacetrapib (compound 9a) as the benchmark, researchers studied how substituting the central phenyl ring of the biphenyl oxazolidinone scaffold affects cholesteryl ester transfer protein (CETP) inhibition. Replacing the trifluoromethyl group of 9a with other substituents significantly changed in vitro CETP inhibitory potency, and analogs bearing certain small groups matched or exceeded the CF3 derivative in potency. Five of the new analogs significantly raised HDL-C (by more than 20 mg/dL), though none outperformed anacetrapib in vivo. The authors describe the synthesis and biological evaluation of this new series of CETP inhibitors.

Original abstract

SAR studies of the substitution effect on the central phenyl ring of the biphenyl scaffold were carried out using anacetrapib (9a) as the benchmark. The results revealed that the new analogs with substitutions to replace trifluoromethyl (9a) had a significant impact on CETP inhibition in vitro. In fact, analogs with some small groups were as potent or more potent than the CF(3) derivative for CETP inhibition. Five of these new analogs raised HDL-C significantly (>20mg/dL). None of them however was better than anacetrapib in vivo. The synthesis and biological evaluation of these CETP inhibitors are described.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.