Synthesis and SAR investigations of novel 2-arylbenzimidazole derivatives as melanin-concentrating hormone receptor 1 (MCH-R1) antagonists

被引：17
|
作者：
Lim, Chae Jo [1 ]
Kim, Nakjeong [1 ]
Lee, Eun Kyoung [1 ,2 ]
Lee, Byung Ho [1 ]
Oh, Kwang-Seok [1 ]
Yoo, Sung-eun [1 ]
Yi, Kyu Yang [1 ,2 ]
机构：
[1] Korea Res Inst Chem Technol, Bioorgan Sci Div, Taejon 305600, South Korea
[2] Univ Sci & Technol, Dept Med & Pharmaceut Chem, Taejon 305350, South Korea
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 08期
关键词：
Melanin-concentrating hormone (MCH); MCH-R1; antagonists; 2-Arylbenzimidazole; Obesity; FOOD-INTAKE; OBESITY; DISCOVERY; MICE; IDENTIFICATION; SYSTEM; POTENT;
D O I：
10.1016/j.bmcl.2011.02.099
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Compounds containing 2-arybenzimidazole ring systems linked to arylpiperidines were synthesized and evaluated as MCH-R1 antagonists. The results of structure-activity relationship studies led to the identification of compound 4c as a potent MCH-R1 antagonist (IC50 = 1 nM). This compound also has good metabolic stability, and favorable pharmacokinetic and brain penetration properties. However 4c was found to be potent inhibitor of the hERG potassium channel. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2309 / 2312
页数：4
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