New metabolically stable fatty acid amide ligands of cannabinoid receptors: Synthesis and receptor affinity studies

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:16

Article

Urbani, P ; Cavallo, P ; Cascio, MG ; Buonerba, M ; De Martino, G ; Di Marzo, V ; Saturnino, C

关键词: cannabinoid;    anandamide;    CB1;    CB2;    receptor;   

DOI  :  10.1016/j.bmcl.2005.09.023

来源: Elsevier

【 摘 要 】

We investigated the structure-activity relationships for the interactions of fatty acid amide analogs of the endocannabinoid anandamide with human recombinant cannabinoid receptors. Thirty-five novel fatty acid amides were synthesized using five different types of acyl chains and 11 different aromatic amine 'heads.' Although none of the new compounds was a more potent ligand than anandamide, we identified three amine groups capable of improving the metabolic stability of arachidonoylamides and their CB1/CB2 selectivity ratio to over 20-fold, and several aromatic amines capable of improving the affinity of short chain or monosaturated fatty acids for cannabinoid CB1 receptors. For the first time a tertiary amide of arachidonic acid was found to possess moderate affinity (K-i = 300 nM) for cannabinoid CB1, but not CB2, receptors. (c) 2005 Elsevier Ltd. All rights reserved.

【 授权许可】

Free