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

  • J Med Chem. 2010 Mar 25;53(6):2666-70. doi: 10.1021/jm100022r.
Hong C Shen  1 ,  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-Ju Wu ,  Kang Cheng ,  Ning Ren ,  Tian-Quan Cai ,  Qing Chen ,  Junying Wang ,  Michael S Wolff ,  Xinchun Tong ,  Tom G Holt ,  M Gerard Waters ,  Milton L Hammond ,  James R Tata ,  Steven L Colletti
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories,Merck & Co, Inc, Rahway, New Jersey 07065-0900, USA. mail: [email protected]
PMID: 20184326 DOI: 10.1021/jm100022r
Abstract

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.

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