Design, synthesis and biological evaluation of new endocannabinoid transporter inhibitors.

@article{LpezRodrguez2003DesignSA,
  title={Design, synthesis and biological evaluation of new endocannabinoid transporter inhibitors.},
  author={Mar{\'i}a L. L{\'o}pez-Rodr{\'i}guez and Alma Viso and Silvia Ortega‐Guti{\'e}rrez and Christopher John Fowler and Gunnar Tiger and Eva de Lago and Javier Fern{\'a}ndez-Ruiz and Jos{\'e} Antonio Ramos},
  journal={European journal of medicinal chemistry},
  year={2003},
  volume={38 4},
  pages={
          403-12
        }
}
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References

SHOWING 1-10 OF 44 REFERENCES
Design, synthesis and biological evaluation of novel arachidonic acid derivatives as highly potent and selective endocannabinoid transporter inhibitors.
TLDR
A series of arachidonic acid derivatives of general structure I which have been characterized as highly potent and selective inhibitors of anandamide transporter deserves special attention as being the most potent endocannabinoid transporter inhibitor described to date.
Structure—Activity Relationships Among N‐Arachidonylethanolamine (Anandamide) Head Group Analogues for the Anandamide Transporter
TLDR
The structural requirements for ligandbinding to the CB1 receptor and binding to the transporter are very different; however, the transporter and FAAH share most, but not all, structural requirements.
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.
2-amino-4H-3,1-benzoxazin-4-ones as inhibitors of C1r serine protease.
TLDR
A series of 2-amino-4H-3,1-benzoxazin-4-ones have been synthesized and evaluated as inhibitors of the complement enzyme C1r, and many of these active compounds show improved potency compared to the reference compound FUT-175.
Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor.
TLDR
Virodhamine produced hypothermia in the mouse and acted as an antagonist in the presence of anandamide both in vivo and in vitro, adding a new form of regulation to the endocannabinoid system.
Effects of homologues and analogues of palmitoylethanolamide upon the inactivation of the endocannabinoid anandamide
TLDR
Palmitoylisopropylamide may prove useful as a template for design of compounds that reduce the cellular accumulation and metabolism of AEA without affecting either CB1 or CB2 receptors.
Cannabinoid receptor ligands: clinical and neuropharmacological considerations, relevant to future drug discovery and development
  • R. Pertwee
  • Biology, Chemistry
    Expert opinion on investigational drugs
  • 2000
This review highlights some important advances that have taken place in cannabinoid research over the last four years. It focuses on novel ligands that are of interest either as experimental tools or
...
...