New resorcinol-anandamide "hybrids" as potent cannabinoid receptor ligands endowed with antinociceptive activity in vivo.

@article{Brizzi2009NewR,
  title={New resorcinol-anandamide "hybrids" as potent cannabinoid receptor ligands endowed with antinociceptive activity in vivo.},
  author={Antonella Brizzi and Vittorio Brizzi and Maria Grazia Cascio and Federico Corelli and Francesca Guida and Alessia Ligresti and Sabatino Maione and Adriano Martinelli and Serena Pasquini and Tiziano Tuccinardi and Vincenzo Di Marzo},
  journal={Journal of medicinal chemistry},
  year={2009},
  volume={52 8},
  pages={
          2506-14
        }
}
Bearing in mind the pharmacophoric requirements of both (-)-trans-Delta(9)-tetrahydrocannabinol (THC) and anandamide (AEA), we designed a novel pharmacophore consisting of both a rigid aromatic backbone and a flexible chain with the aim to develop a series of stable and potent ligands of cannabinoid receptors. In this paper we report the synthesis, docking studies, and structure-activity relationships of new resorcinol-anandamide "hybrids" differing in the side chain group. Compounds bearing a… Expand
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References

SHOWING 1-10 OF 61 REFERENCES
A structure/activity relationship study on arvanil, an endocannabinoid and vanilloid hybrid.
TLDR
The findings suggest that VR1 and/or as yet uncharacterized receptors produce cannabimimetic responses in mice in vivo. Expand
Design, synthesis, and binding studies of new potent ligands of cannabinoid receptors.
TLDR
This study 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, and showed that some of the newly developed compounds have high affinity and specificity for cannabinoid CB1 and CB2 receptors. Expand
Structure-activity analysis of anandamide analogs: relationship to a cannabinoid pharmacophore.
TLDR
When eight pharmacologically active anandamide analogs are aligned to delta 9-THC according to the proposed pharmacophore overlay, their potencies are predicted by a quantitative model of cannabinoid structure--activity relationships based solely on classical and nonclassical cannabinoids with a reasonable degree of accuracy. Expand
Cannabimimetic fatty acid derivatives: the anandamide family and other endocannabinoids.
TLDR
The metabolic pathways suggested so far to underlie the biosynthesis and inactivation of anandamide and 2-AG and the current knowledge of the chemical bases for the interactions of an andamide with proteins of the endogenous cannabinoid system characterized so far are reviewed. Expand
Design, synthesis, binding, and molecular modeling studies of new potent ligands of cannabinoid receptors.
TLDR
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
Synthesis and pharmacological comparison of dimethylheptyl and pentyl analogs of anandamide.
TLDR
The data indicate a structural equivalence between classical plant cannabinoids and 2a as well as different receptor-ligand interactions that characterize multiple receptor sites or binding modes. Expand
Pharmacophoric requirements for cannabinoid side chains: multiple bond and C1'-substituted delta 8-tetrahydrocannabinols.
TLDR
The synthesis and affinities for the CB1 and CB2 receptors of a series of novel delta 8-THC analogues in which the side-chain pharmacophores are conformationally more defined than in the parent molecule are described. Expand
Molecular characterization of a peripheral receptor for cannabinoids
TLDR
The cloning of a receptor for cannabinoids is reported that is not expressed in the brain but rather in macrophages in the marginal zone of spleen, which helps clarify the non-psychoactive effects of cannabinoids. Expand
Indoles and related compounds as cannabinoid ligands.
TLDR
This review reports the main aminoalkylindole derivatives, and other compounds which are hypothesized to interact in the same binding site, and analyses the pharmacological profiles, the mutagenesis data and computational models that describe their interaction in the cannabinoid receptors. Expand
Natural cannabinoids: templates for drug discovery.
TLDR
The C-3 side chain is identified as the key pharmacophore for ligand affinity and selectivity for the known cannabinoid receptors and for pharmacological potency in cannabinoids and endocannabinoids. Expand
...
1
2
3
4
5
...