2-Arylbenzoxazoles as CETP inhibitors: Raising HDL-C in cynoCETP transgenic mice

…, J Kowalchick, YJ Park, JA Hunt, A Ali, CJ Smith…

Index: Kallashi, Florida; Kim, Dooseop; Kowalchick, Jennifer; Park, You Jung; Hunt, Julianne A.; Ali, Amjad; Smith, Cameron J.; Hammond, Milton L.; Pivnichny, James V.; Tong, Xinchun; Xu, Suoyu S.; Anderson, Matt S.; Chen, Ying; Eveland, Suzanne S.; Guo, Qiu; Hyland, Sheryl A.; Milot, Denise P.; Cumiskey, Anne-Marie; Latham, Melanie; Peterson, Laurence B.; Rosa, Raymond; Sparrow, Carl P.; Wright, Samuel D.; Sinclair, Peter J. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 1 p. 558 - 561

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Citation Number: 21

Abstract

We describe structure–activity studies leading to the discovery of 2-arylbenzoxazole 3, the first in a series to raise serum high-density lipoprotein cholesterol levels in transgenic mice. Replacement of the 4-piperidinyloxy moiety with piperazinyl provided a more synthetically tractable lead, which upon optimization resulted in compound 4, an excellent inhibitor of cholesteryl ester transfer protein function with good pharmacokinetic properties and in ...