Novel norsufentanil analogues containing triazole ring; synthesis, radioligand binding assay, and pharmacological evaluation.

A series of 12 novel triazoles containing derivatives of norsufentanil were put into synthesis having the construction of the alkynyl group on norsufentanil followed by copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. Every single one of the synthesized compounds was evaluated through radioligand binding experiments. The compounds with the best affinities in the in vitro studies were selected to be investigated for their anti-nociceptive activity by way of tail flick test. Compounds 3h and 3i (Ki = 0.55 nM; IC₅₀ = 1.25 nM and, Ki = 0.83 nM; IC₅₀ = 1.87 nM, respectively) displayed the best affinities compared to that of sufentanil's (K_i = 0.70 nM; IC₅₀ = 1.59 nM). 3h put on display the highest potency (ED₅₀ = 4.21 µg/kg) for tail flick test amongst the entire selected compounds. [ABSTRACT FROM AUTHOR]