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

Bioorg Med Chem Lett. 2013 Aug 15;23(16):4713-8. doi: 10.1016/j.bmcl.2013.05.081. Epub 2013 Jun 4.

Abstract

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 4weeks study with DIO mouse model.

Keywords: Aminobenzimidazole; DGAT-1; Diabetes; Diacylglycerol acyltransferase-1; Obesity; TG; Triglycerides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetic Acid / chemistry*
  • Animals
  • Anti-Obesity Agents / chemical synthesis
  • Anti-Obesity Agents / pharmacology
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Cells, Cultured
  • Cyclization
  • Diabetes Mellitus / drug therapy
  • Disease Models, Animal
  • Humans
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / pharmacology
  • Liver / drug effects
  • Mice
  • Molecular Structure
  • Obesity / drug therapy

Substances

  • Anti-Obesity Agents
  • Benzimidazoles
  • Hypoglycemic Agents
  • 2-aminobenzimidazole
  • Acetic Acid