In this study, we developed a simple, solvent- and metal-free one-pot method to synthesize 4-acyl-1,2,3-triazoles from readily available acetophenones and various aryl azides.Thirty-three compounds were obtained with yields ranging from 40 to 82 % within 2 h under thermal conditions.This research also investigates these compounds as precursors to bioactive hydroxy-1,2,3-triazoles, aiming to identify new drug candidates for Cystic Fibrosis (CF) treatment.Specifically, we evaluated their ability to rescue the common CF-causing variant p.Phe508del-CFTR.Two new compounds, LSO-162 and LSO-168, successfully rescued p.Phe508del-CFTR trafficking with EC50 values of 2.41 and 1.91 μM, resp.For comparison, the clin. approved drug VX-445, a compound in a triple combination therapy, has an EC50 of 0.245 μM.Computational studies provided insights into the structure-activity relationship, particularly the role of carbonylated and hydroxylated triazole-based compounds as potential new p.Phe508del-CFTR traffic correctors.These findings highlight the potential for developing new, effective CF treatments.