Design, synthesis and structure–activity-relationship of 1, 5-tetrahydronaphthyridines as CETP inhibitors

…, X Wang, SL Cockerham, TP Beyer, RJ Schmidt…

Index: Fernandez, Maria-Carmen; Escribano, Ana; Mateo, Ana I.; Parthasarathy, Saravanan; Martin De La Nava, Eva M.; Wang, Xiaodong; Cockerham, Sandra L.; Beyer, Thomas P.; Schmidt, Robert J.; Cao, Guoqing; Zhang, Youyan; Jones, Timothy M.; Borel, Anthony; Sweetana, Stephanie A.; Cannady, Ellen A.; Stephenson, Gregory; Frank, Scott; Mantlo, Nathan B. Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 9 p. 3056 - 3062

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Citation Number: 13

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 (IC50= 23 and 22nM, respectively). Both 21b and 21d exhibited robust HDL-c increase in hCETP/hApoA1 dual heterozygous mice model.