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

  • Kwak, Hyun Jung
  • Pyun, Yu Mi
  • Kim, Ji Young
  • Pagire, Haushabhau S.
  • Kim, Ki Young
  • ... Lee, Duck Hyung
  • 외 6명
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초록

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.

키워드

Diacylglycerol acyltransferase-1DGAT-1TriglyceridesTGObesityDiabetesAminobenzimidazoleCOA-DIACYLGLYCEROL ACYLTRANSFERASETRIGLYCERIDE SYNTHESISKEY ENZYMEOBESITYMICEIDENTIFICATIONINHIBITIONPOTENTDGAT1
제목
Synthesis and biological evaluation of aminobenzimidazole derivatives with a phenylcyclohexyl acetic acid group as anti-obesity and anti-diabetic agents
저자
Kwak, Hyun JungPyun, Yu MiKim, Ji YoungPagire, Haushabhau S.Kim, Ki YoungKim, Kwang RokDal Rhee, SangJung, Won HoonSong, Jin SookBae, Myung AeLee, Duck HyungAhn, Jin Hee
DOI
10.1016/j.bmcl.2013.05.081
발행일
2013-08-15
유형
Article
저널명
Bioorganic and Medicinal Chemistry Letters
23
16
페이지
4713 ~ 4718