Synthesis and biological evaluation of aminobenzimidazole derivatives with a phenylcyclohexyl acetic acid group as anti-obesity and anti-diabetic agents

被引：41

作者：

Kwak, Hyun Jung ^{[1
]}

Pyun, Yu Mi ^{[2
]}

Kim, Ji Young ^{[1
,3
]}

Pagire, Haushabhau S. ^{[1
,3
]}

Kim, Ki Young ^{[1
]}

Kim, Kwang Rok ^{[1
]}

Dal Rhee, Sang ^{[1
]}

Jung, Won Hoon ^{[1
]}

Song, Jin Sook ^{[1
]}

Bae, Myung Ae ^{[1
]}

Lee, Duck Hyung ^{[2
]}

Ahn, Jin Hee ^{[1
]}

机构：

[1] Korea Res Inst Chem Technol, Drug Discovery Div, Taejon 305600, South Korea

[2] Sogang Univ, Dept Chem, Seoul 121742, South Korea

[3] Univ Sci & Technol, Dept Med & Pharmaceut Chem, Taejon 305333, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 16期

基金：

新加坡国家研究基金会;

关键词：

Diacylglycerol acyltransferase-1; DGAT-1; Triglycerides; TG; Obesity; Diabetes; Aminobenzimidazole; COA-DIACYLGLYCEROL ACYLTRANSFERASE; TRIGLYCERIDE SYNTHESIS; KEY ENZYME; OBESITY; MICE; IDENTIFICATION; INHIBITION; POTENT; DGAT1;

D O I：

10.1016/j.bmcl.2013.05.081

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of benzimidazole derivatives with a phenylcyclohexyl acetic acid group as DGAT-1 inhibitors was developed. Among the benzimidazole series, compound 5k showed submicromolar in vitro activity toward human and mouse DGAT-1, good selectivity toward DGAT-2, human liver metabolic stability, and pharmacokinetic (PK) and safety profiles such as hERG, CYP and acute toxicity. Additionally, 5k showed good in vivo efficacy in 4 weeks study with DIO mouse model. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：4713 / 4718

页数：6

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