Synthesis and binding study of certain 6-arylalkanamides as molecular probes for cannabinoid receptor subtypes

Abstract

Tetrahydrocannabinol and other mixed cannabinoid (CB) receptors CB₁/CB₂ receptor agonists are well established to elicit antinociceptive effects and psychomimetic actions, however, their potential for abuse have dampened enthusiasm for their therapeutic development. In an effort to refine a semi-rigid structural framework for CB₂ receptors binding, we designed 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. In this direction, we developed and synthesized new aryl or arylidene hexanoic acid amides and aryl alkanoic acid diamide carrying different head groups. These new compounds were tested for their affinities for human recombinant CB receptors CB₁ and CB₂ and fatty acid amide hydrolase. Although, the preliminary screening of these compounds demonstrated weak binding activity towards CB receptor subtypes at 10 µmole, yet this template still could serve up as probes for further optimization and development of affinity ligand for CB receptors.

Keywords::

• Cannabinoid
• selective CB₂ ligands
• synthesis

Acknowledgment

The authors are grateful to the staff members micro-analytical unit, Cairo University for performing the spectra data for the synthesized compounds.

Declaration of interest

The authors report no conflict of interest.