Tetrahydronaphthyridine CETP inhibitors reach nanomolar potency and raise HDL-C in transgenic mice (Bioorg Med Chem Lett 2012)

Original title: Design, synthesis and structure-activity-relationship of 1,5-tetrahydronaphthyridines as CETP inhibitors

Bioorg Med Chem Lett · 28 March 2012 · 5

Fernandez MC, Escribano A, Mateo AI, Parthasarathy S, Martin de la Nava EM, Wang X, Cockerham SL, Beyer TP, Schmidt RJ, Cao G, Zhang Y, Jones TM et al.

Researchers discovered and optimised 1,5-tetrahydronaphthyridines as a new class of CETP inhibitors, identifying lead compounds 21b and 21d with in vitro human plasma CETP inhibitory activity in the nanomolar range (IC50 of 23 and 22 nanomolar, respectively). Both compounds produced robust increases in HDL cholesterol in a dual heterozygous hCETP/hApoA1 transgenic mouse model. The findings identify tetrahydronaphthyridines as a promising new structural class for CETP inhibitor development.

Original abstract

This Letter describes the discovery and SAR optimization of 1,5-tetrahydronaphthyridines, a new class of potent CETP inhibitors. The effort led to the identification of 21b and 21d with in vitro human plasma CETP inhibitory activity in the nanomolar range (IC(50)=23 and 22nM, respectively). Both 21b and 21d exhibited robust HDL-c increase in hCETP/hApoA1 dual heterozygous mice model.

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