Design, synthesis, and binding studies of new potent ligands of cannabinoid receptors.

  title={Design, synthesis, and binding studies of new potent ligands of cannabinoid receptors.},
  author={Antonella Brizzi and Vittorio Brizzi and Maria Grazia Cascio and Tiziana Bisogno and Rossella Sirianni and Vincenzo Di Marzo},
  journal={Journal of medicinal chemistry},
  volume={48 23},
Despite their different chemical structures, delta9-tetrahydrocannabinol (THC) and anandamide (AEA) have common pharmacological properties. This study was aimed at finding new cannabinoid receptor ligands that overcome the instability of AEA and its analogues. To this end we planned the synthesis of a series of compounds which retained both a rigid structure, like that of plant cannabinoids, and a flexible portion similar to that of anandamide. Binding studies on CB1 and CB2 receptors… Expand
Synthesis and binding study of certain 6-arylalkanamides as molecular probes for cannabinoid receptor subtypes
Novel compounds based on aromatic moiety and flexible linker with various amides mimicking the outlook of the endogenous anandamide which could provide as CB2 receptor ligand are designed in an effort to refine a semi-rigid structural framework for CB2 receptors binding. Expand
Structure-affinity relationships and pharmacological characterization of new alkyl-resorcinol cannabinoid receptor ligands: Identification of a dual cannabinoid receptor/TRPA1 channel agonist.
Binding studies on CB1 and CB2 receptors, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) showed that some of the newly developed compounds behaved as very potent cannabinoid receptor ligands while, however, none of them was able to inhibit MAGL and/or FAAH. Expand
Design, synthesis, binding, and molecular modeling studies of new potent ligands of cannabinoid receptors.
Compounds with amidic 'heads' with alkyloxy chains varying in length from 8 to 12 carbon atoms showed nanomolar affinity for both receptors, depending on the type of aromatic backbone, and two of the new compounds exhibit selectivity for CB(1) receptors. Expand
New resorcinol-anandamide "hybrids" as potent cannabinoid receptor ligands endowed with antinociceptive activity in vivo.
The synthesis, docking studies, and structure-activity relationships of new resorcinol-anandamide "hybrids" differing in the side chain group are reported, with results similar to that of WIN 55-212. Expand
Fluorinated cannabinoid CB2 receptor ligands: synthesis and in vitro binding characteristics of 2-oxoquinoline derivatives.
Preliminary in vitro results suggest that six of these compounds may be useful for therapy of neuropathic pain, neuroinflammatory diseases and immune disorders. Expand
Cannabinoid receptor 1 ligands revisited: Pharmacological assessment in the ACTOne system.
The first detailed evaluation of the ACTOne assay for the pharmacological evaluation of CB1 ligands is reported, revealing some interesting deviations from previously reported functional activities of the aforementioned ligands. Expand
Novel sterically hindered cannabinoid CB1 receptor ligands.
This compound is the first of a novel class of tetraphenyl CB( 1) ligands that, in view of its easy synthesis and high affinity for CB(1) receptors and despite its sterical hindrance, will be useful for the design of new blockers of this therapeutically exploitable receptor type. Expand
Resorcinol-sn-glycerol derivatives: novel 2-arachidonoylglycerol mimetics endowed with high affinity and selectivity for cannabinoid type 1 receptor.
The cannabinoid receptor binding properties, the CB1 functional activity, and the stability to plasma esterases of a novel series of compounds characterized by the conversion of the amide head into the glycerol-ester or glycerl-ether head, typical of 2-AG or the "putative" endocannabinoid 2-AGE, respectively are explored. Expand
Investigations on the 4-quinolone-3-carboxylic acid motif. 6. Synthesis and pharmacological evaluation of 7-substituted quinolone-3-carboxamide derivatives as high affinity ligands for cannabinoid receptors.
A new series of compounds characterized by a fluoro or phenylthio group at 7-position and different substituents at N1 and carboxamide nitrogen were synthesized and evaluated for their binding ability to cannabinoid type 1 (CB1) and type 2 (CB2) receptors. Expand
Recent advances in the development of selective ligands for the cannabinoid CB(2) receptor.
This review will discuss the current advances and recent results in the structure-activity relationships (SAR) of selective ligands for the cannabinoid CB(2) receptor. Expand