Chemical Characterization and in vitro Metabolism of a Novel Class of Delta Opioid Receptor Agonists, Analogs of SNC‐80

Abstract

The diazatricyclodecane derivatives belong to a novel class of δ opioid receptor agonists, conformationally restricted analogs of SNC‐80. To support further investigation on the potential use of this class of δ opioid receptor agonists in humans, synthesis and chemical characterization of three tricyclic compounds of this class, designated as 3–4‐5, was carried out. Moreover, drug metabolism of the same compounds was investigated using human liver microsomes. Being drug candidates chiral compounds, they were also evaluated in terms of stereoisomers presence in the drug substances. Pharmacokinetic profiles and kinetic parameters of compound 3 and compound 4 and Michaelis parameters of compound 3 were determined. Remaining percentages of the parent drug versus time were analyzed. Results indicated that the examined derivatives display good in vitro metabolic stability.

An updated synthesis of N1′‐([11C]methyl)naltrindole for positron emission tomography imaging of the delta opioid receptor

“…In the CNS, DORs are found in the cerebral cortex, caudate putamen, and the nucleus accumbens 6 . Activation of DORs results in many physiological and behavioral effects including modulation of antinociception, mood, sensory system, motor integration, and cognitive functions 6,17 . In addition, DORs are also present in several immunocompetent cells, which suggests their pivotal role in regulating the immune system 18 .…”