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.
M L López-Rodríguez  1 ,  A Viso ,  S Ortega-Gutiérrez ,  I Lastres-Becker ,  S González ,  J Fernández-Ruiz ,  J A Ramos
Affiliations
  • 1. Departamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense, 28040 Madrid, Spain. [email protected]
PMID: 11741470 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.