Design and synthesis of (13S)-methyl-substituted arachidonic acid analogues: templates for novel endocannabinoids.
Two novel methyl-substituted arachidonic acid derivatives were prepared in an enantioselective manner from commercially available chiral building blocks, and were found to be excellent templates for the development of (13S)-methyl-substituted anandamide analogues. One of the compounds synthesized, namely, (13S,5Z,8Z,11Z,14Z)-13-methyl-eicosa-5,8,11,14-tetraenoic acid N-(2-hydroxyethyl)amide, is an endocannabinoid analogue with remarkably high affinity for the CB1 cannabinoid receptor.
Papahatjis
Demetris P
DP
Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vass. Constantinou, Athens 116-35, Greece. dpapah@eie.gr
Nahmias
Victoria R
VR
Nikas
Spyros P
SP
Schimpgen
Marion
M
Makriyannis
Alexandros
A
D000478:Alkylation; D016718:Arachidonic Acid / Q000138:chemical synthesis* / Q000737:chemistry; D001095:Arachidonic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D063385:Cannabinoid Receptor Modulators / Q000737:chemistry* / Q000378:metabolism; D063388:Endocannabinoids; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D043884:Receptor, Cannabinoid, CB1 / Q000737:chemistry* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C550434:(13S,5Z,8Z,11Z,14Z)-13-methyl-eicosa-5,8,11,14-tetraenoic acid N-(2-hydroxyethyl)amide; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D016718:Arachidonic Acid