2-hydroxy-N-arylbenzenesulfonamides as ATP-citrate lyase inhibitors

Bioorg Med Chem Lett. 2007 Jun 1;17(11):3208-11. doi: 10.1016/j.bmcl.2007.03.017. Epub 2007 Mar 12.

Abstract

A novel series of 2-hydroxy-N-arylbenzenesulfonamides were identified to be ATP-citrate lyase (ACL) inhibitors with compound 9 displaying potent in vitro activity (IC(50)=0.13 microM). Chronic oral dosing of compound 9 in high-fat fed mice lowered plasma cholesterol, triglyceride, and glucose, as well as inhibited weight gain.

MeSH terms

  • ATP Citrate (pro-S)-Lyase / antagonists & inhibitors*
  • Adipose Tissue / drug effects
  • Animals
  • Anti-Obesity Agents / chemical synthesis
  • Anti-Obesity Agents / chemistry*
  • Anti-Obesity Agents / pharmacology*
  • Benzene / chemistry*
  • Blood Glucose / analysis
  • Body Weight / drug effects
  • Cells, Cultured
  • Cholesterol / blood
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Mice
  • Rats
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology*
  • Triglycerides / blood

Substances

  • Anti-Obesity Agents
  • Blood Glucose
  • Enzyme Inhibitors
  • Sulfonamides
  • Triglycerides
  • Cholesterol
  • ATP Citrate (pro-S)-Lyase
  • Benzene