1415573-45-3Relevant academic research and scientific papers
Discovery of a potent and selective DGAT1 inhibitor with a piperidinyl-oxy-cyclohexanecarboxylic acid moiety
He, Shuwen,Hong, Qingmei,Lai, Zhong,Yang, David X.,Ting, Pauline C.,Kuethe, Jeffrey T.,Cernak, Timothy A.,Dykstra, Kevin D.,Sperbeck, Donald M.,Wu, Zhicai,Yu, Yang,Yang, Ginger X.,Jian, Tianying,Liu, Jian,Guiadeen, Deodial,Krikorian, Arto D.,Sonatore, Lisa M.,Wiltsie, Judyann,Liu, Jinqi,Gorski, Judith N.,Chung, Christine C.,Gibson, Jack T.,Lisnock, Jeanmarie,Xiao, Jianying,Wolff, Michael,Tong, Sharon X.,Madeira, Maria,Karanam, Bindhu V.,Shen, Dong-Ming,Balkovec, James M.,Pinto, Shirly,Nargund, Ravi P.,Devita, Robert J.
, p. 1082 - 1087 (2014/12/10)
We report the discovery of a novel series of DGAT1 inhibitors in the benzimidazole class with a piperdinyl-oxy-cyclohexanecarboxylic acid moiety. This novel series possesses significantly improved selectivity against the A2A receptor, no ACAT1 off-target activity at 10 μM, and higher aqueous solubility and free fraction in plasma as compared to the previously reported pyridyl-oxy-cyclohexanecarboxylic acid series. In particular, 5B was shown to possess an excellent selectivity profile by screening it against a panel of more than 100 biological targets. Compound 5B significantly reduces lipid excursion in LTT in mouse and rat, demonstrates DGAT1 mediated reduction of food intake and body weight in mice, is negative in a 3-strain Ames test, and appears to distribute preferentially in the liver and the intestine in mice. We believe this lead series possesses significant potential to identify optimized compounds for clinical development.
IMIDAZOLE DERIVATIVES
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Page/Page column 58-59, (2013/02/27)
Described herein are compounds of formula (I), The compounds of formula I act as DGAT1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for hyperlipidemia, diabetes mellitus and obesity.
