Design, synthesis and biological evaluation of novel arachidonic acid derivatives as highly potent and selective endocannabinoid transporter inhibitors

J Med Chem. 2001 Dec 20;44(26):4505-8. doi: 10.1021/jm015545y.

Abstract

In the present work, we have designed and synthesized a series of arachidonic acid derivatives of general structure I which have been characterized as highly potent and selective inhibitors of anandamide transporter (IC(50) = 24-0.8 microM, K(i) > 1000-5000 nM for CB(1) and CB(2) cannabinoid receptors and vanilloid VR(1) receptor). Among them, N-(3-furylmethyl)eicosa-5,8,11,14-tetraenamide deserves special attention as being the most potent endocannabinoid transporter inhibitor (IC(50) = 0.8 microM) described to date.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acids / chemical synthesis*
  • Arachidonic Acids / chemistry
  • Arachidonic Acids / metabolism
  • Arachidonic Acids / pharmacology
  • Cannabinoid Receptor Modulators
  • Cannabinoids / metabolism*
  • Carrier Proteins / antagonists & inhibitors*
  • Carrier Proteins / metabolism
  • Cell Line
  • Cerebellum / metabolism
  • Drug Design
  • Endocannabinoids
  • Furans / chemical synthesis*
  • Furans / chemistry
  • Furans / pharmacology
  • Humans
  • In Vitro Techniques
  • Membranes
  • Polyunsaturated Alkamides
  • Radioligand Assay
  • Receptors, Cannabinoid
  • Receptors, Drug / metabolism
  • Spinal Cord / metabolism
  • Structure-Activity Relationship

Substances

  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Carrier Proteins
  • Endocannabinoids
  • Furans
  • N-(3-furylmethyl)eicosa-5,8,11,14-tetraenamide
  • Polyunsaturated Alkamides
  • Receptors, Cannabinoid
  • Receptors, Drug
  • anandamide