Discovery of a biaryl cyclohexene carboxylic acid (MK-6892): A potent and selective high affinity niacin receptor full agonist with reduced flushing profiles in animals as a preclinical candidate
Biaryl cyclohexene carboxylic acids were discovered as full and potent niacin receptor (GPR 109A) agonists. Compound 1e (MK-6892) displayed excellent receptor activity, good PK across species, remarkably clean off-target profiles, good ancillary pharmacology, and superior therapeutic window over niacin regarding the FFA reduction versus vasodilation in rats and dogs.
Shen, Hong C.,Ding, Fa-Xiang,Raghavan, Subharekha,Deng, Qiaolin,Luell, Silvi,Forrest, Michael J.,Carballo-Jane, Ester,Wilsie, Larissa C.,Krsmanovic, Mihajlo L.,Taggart, Andrew K.,Wu, Kenneth K.,Wu, Tsuei-Ju,Cheng, Kang,Ren, Nina,Cai, Tian-Quan,Chen, Qing,Wang, Junying,Wolff, Michael S.,Tong, Xinchun,Holt, Tom G.,Waters, M.Gerard,Hammond, Milton L.,Tata, James R.,Colletti, Steven L.
supporting information; experimental part
p. 2666 - 2670
(2010/08/22)
Niacin receptor agonists, compositions containing such compounds and methods of treatment
The present invention encompasses compounds of Formula I: as well as pharmaceutically acceptable salts and hydrates thereof, that are useful for treating atherosclerosis, dyslipidemias and the like. Pharmaceutical compositions and methods of use are also included.
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Page/Page column 29; 49
(2010/11/25)
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