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

共 50 条

[1] DGAT1 inhibitors as anti-obesity and anti-diabetic agents
Birch, Alan M.
Buckett, Linda K.
Turnbull, Andrew V.
CURRENT OPINION IN DRUG DISCOVERY & DEVELOPMENT, 2010, 13 (04) : 489 - 496
[2] Synthesis and biological evaluation of chalcone derivatives as a novel class of anti-diabetic agents
Hsieh, C. T.
Hsieh, T. J.
Wu, Y. C.
Chang, F. R.
PLANTA MEDICA, 2012, 78 (11) : 1109 - 1109
[3] Anti-Obesity and Anti-Diabetic Effects of Lichochalcone A
Quan, Hai Yan
Kim, Soo Jung
Kim, Go Woon
Kim, Do Yeon
Chung, Sung Hyun
DIABETES, 2012, 61 : A459 - A459
[4] Synthesis and biological evaluation of 3-arylcoumarin derivatives as potential anti-diabetic agents
Hu, Yuheng
Wang, Bing
Yang, Jie
Liu, Teng
Sun, Jie
Wang, Xiaojing
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2019, 34 (01) : 15 - 30
[5] ANTI-OBESITY AND ANTI-DIABETIC EFFECT OF ALLENIC CAROTENOID
Okada, Tomoko
Maeda, Hayato
Hosokawa, Masashi
Miyashita, Kazuo
ANNALS OF NUTRITION AND METABOLISM, 2009, 55 : 92 - 92
[6] Anti-obesity and anti-diabetic actions of histamine neurons
中国病理生理杂志, 2001, (08) : 66 - 66
[7] Anti-obesity and anti-diabetic effects of nitrate and nitrite
Ghasemi, Asghar
Jeddi, Sajad
NITRIC OXIDE-BIOLOGY AND CHEMISTRY, 2017, 70 : 9 - 24
[8] Anti-obesity and anti-diabetic actions of histamine neurons
中国病理生理杂志, 2001, (09) : 108 - 108
[9] Anti-Obesity and Anti-Diabetic Effects of Ishige okamurae
Yang, Hye-Won
Fernando, K. H. N.
Oh, Jae-Young
Li, Xining
Jeon, You-Jin
Ryu, BoMi
MARINE DRUGS, 2019, 17 (04)
[10] A Hamster Model of Diet-Induced Obesity for Preclinical Evaluation of Anti-Obesity, Anti-Diabetic and Lipid Modulating Agents
Dalboge, Louise S.
Pedersen, Philip J.
Hansen, Gitte
Fabricius, Katrine
Hansen, Henrik B.
Jelsing, Jacob
Vrang, Niels
PLOS ONE, 2015, 10 (08):

← 1 2 3 4 5 →