1093685-70-1Relevant articles and documents
2-(4-Carbonylphenyl)benzoxazole inhibitors of CETP: Attenuation of hERG binding and improved HDLc-raising efficacy
Sweis, Ramzi F.,Hunt, Julianne A.,Sinclair, Peter J.,Chen, Ying,Eveland, Suzanne S.,Guo, Qiu,Hyland, Sheryl A.,Milot, Denise P.,Cumiskey, Anne-Marie,Latham, Melanie,Rosa, Raymond,Peterson, Larry,Sparrow, Carl P.,Anderson, Matt S.
scheme or table, p. 2597 - 2600 (2011/06/20)
The development of 2-phenylbenzoxazoles as inhibitors of cholesteryl ester transfer protein (CETP) is described. Efforts focused on finding suitable replacements for the central piperidine with the aim of reducing hERG binding: a main liability of our benchmark benzoxazole (1a). Replacement of the piperidine with a cyclohexyl group successfully attenuated hERG binding, but was accompanied by reduced in vivo efficacy. The approach of substituting a piperidine moiety with an oxazolidinone also attenuated hERG binding. Further refinement of this latter scaffold via SAR at the pyridine terminus and methyl branching on the oxazolidinone led to compounds 7e and 7f, which raised HDLc by 33 and 27 mg/dl, respectively, in our transgenic mouse PD model and without the hERG liability of previous series.
CETP INHIBITORS DERIVED FROM BENZOXAZOLE ARYLAMIDES
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Page/Page column 47, (2009/01/23)
Compounds having the structure of Formula I, including pharmaceutically acceptable salts of the compounds, are potent CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis. In formula I, A-B is an arylamide moiety.
