发现一种联芳环己烯羧酸（MK-6892）：一种具有高亲和力烟碱受体的有效且选择性的全激动剂，在动物中具有较低的潮红特征，是一种临床前候选药物。
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.
机构信息
Department of Medicinal Chemistry, Merck Research Laboratories,Merck & Co, Inc, Rahway, New Jersey 07065-0900, USA. mail:
出版信息
J Med Chem. 2010 Mar 25;53(6):2666-70. doi: 10.1021/jm100022r.
PMID:20184326
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.
摘要
双环己烯羧酸类被发现是全效且强效的烟酸受体（GPR109A）激动剂。化合物 1e（MK-6892）表现出优异的受体活性、良好的跨物种 PK 特性、显著的非靶点特性、良好的辅助药理学特性，以及在大鼠和犬中降低游离脂肪酸与血管扩张方面相对于烟酸的优异治疗窗口。
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