1 research outputs found
Synthesis and Structure–Activity Relationship Study of a New Series of Selective σ<sub>1</sub> Receptor Ligands for the Treatment of Pain: 4‑Aminotriazoles
The
synthesis and pharmacological activity of a new series of 4-aminotriazoles
as potent σ<sub>1</sub> receptor (σ<sub>1</sub>R) ligands
are reported. The compounds were prepared using a 4–5-step
process, involving as a key step a click chemistry reaction between
ynamides and azides. The most active compounds exhibited nanomolar
potency for the σ<sub>1</sub>R, and the selectivity over the
σ<sub>2</sub>R was improved on decreasing the central amine
basicity. It was concluded that in order to achieve good σ<sub>1</sub>R potency a minimum lipophilicity was required, while limiting
to a defined range of cLog<i>P</i> avoided human ether-a-go-go-related
gene channel inhibition. This made the most interesting derivatives
to be concentrated in a narrow margin of lipophilicity. Among them,
compound <b>13g</b> exhibited the most potent in vivo antinociceptive
properties, which are indicative of its antagonist character