title: 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.
authors.affiliation: Zhongnan Hospital of Wuhan University, Department of Anesthesiology, Wuhan University, Wuhan 430071, China. ranyanqwe@sina.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ran
authors.affiliation: Department of Doppler Ultrasound, PLA421 Hospital, Guangzhou 510318, China. liming8782@sina.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Zhongnan Hospital of Wuhan University, Department of Anesthesiology, Wuhan University, Wuhan 430071, China. zhongzongze@hotmail.com.
authors.forename: Zong-Ze
authors.initials: ZZ
authors.lastname: Zhang
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D002384:Catalysis; D003315:Cornea / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D011817:Rabbits; D013451:Sulfonic Acids / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000779:Anesthetics, Local; D007093:Imidazoles; D013451:Sulfonic Acids; D047392:beta-Cyclodextrins; C029899:imidazole; D008012:Lidocaine; C031215:betadex
keywords: imidazoles; local anesthetic agent; synthesis