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
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- 作者：Hong C. Shen ; Fa-Xiang Ding ; Subharekha Raghavan ; Qiaolin Deng ; Silvi Luell ; Michael J. Forrest ; Ester Carballo-Jane ; Larissa C. Wilsie ; Mihajlo L. Krsmanovic ; Andrew K. Taggart ; Kenneth K. Wu ; Tsuei-
- 刊名：Journal of Medicinal Chemistry
- 出版年：2010
- 出版时间：March 25, 2010
- 年：2010
- 卷：53
- 期：6
- 页码：2666-2670
- 全文大小：875K
- 年卷期：v.53,no.6(March 25, 2010)
- ISSN：1520-4804
文摘
Biaryl cyclohexene carboxylic acids were discovered as full and potent niacin receptor (GPR109A) 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.