A novel monoacylglycerol lipase inhibitor with analgesic and anti-inflammatory activity

Bioorg Med Chem Lett. 2008 Oct 15;18(20):5424-7. doi: 10.1016/j.bmcl.2008.09.039. Epub 2008 Sep 12.

Abstract

A variety of long chain 1,2-diamines and related compounds were synthesized and tested for their activity on fatty acid amide hydrolase (FAAH) and monoacyglycerol lipase (MGL). (2S,9Z)-Octadec-9-ene-1,2-diamine selectively inhibits MGL (K(i) 21.8 microM) without significantly affecting FAAH. This compound exhibited interesting in vivo analgesic and anti-inflammatory properties, suggesting that selective inhibitors of MGL may be valuable novel agents for the treatment of inflammatory pain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / chemistry
  • Analgesics / chemical synthesis*
  • Analgesics / chemistry
  • Analgesics / pharmacology
  • Animals
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / pharmacology
  • Aspirin / pharmacology
  • Cannabinoid Receptor Modulators / chemistry
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Enzyme Inhibitors / pharmacology
  • Indomethacin / chemistry
  • Inflammation
  • Kinetics
  • Models, Chemical
  • Monoacylglycerol Lipases / antagonists & inhibitors*
  • Monoacylglycerol Lipases / chemistry
  • Rats

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Cannabinoid Receptor Modulators
  • Enzyme Inhibitors
  • Monoacylglycerol Lipases
  • Amidohydrolases
  • fatty-acid amide hydrolase
  • Aspirin
  • Indomethacin