β-Cyclodextrin-propyl sulfonic acid catalysed one-pot synthesis of 1,2,4,5-tetrasubstituted imidazoles as local anesthetic agents

Abstract

Some functionalized 1,2,4,5-tetrasubstituted imidazole derivatives were synthesized using a one-pot, four component reaction involving 1,2-diketones, aryl aldehydes, ammonium acetate and substituted aromatic amines. the synthesis has been efficiently carried out in a solvent free medium using β-cyclodextrin-propyl sulfonic acid as a catalyst to afford the target compounds in excellent yields. the local anesthetic effect of these derivatives was assessed in comparison to lidocaine as a standard using a rabbit corneal and mouse tail anesthesia model. the three most potent promising compounds were subjected to a rat sciatic nerve block assay where they showed considerable local anesthetic activity, along with minimal toxicity. among the tested analogues, 4-(1-benzyl-4,5-diphenyl-1h-imidazol-2-yl)-n,n-dimethylaniline (5g) was identified as most potent analogue with minimal toxicity. it was further characterized by a more favourable therapeutic index than the standard.