β–Cyclodextrin–Propyl Sulfonic Acid Catalysed One-Pot Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles as Local Anesthetic Agents

Molecules

Yan Ran²  Ming Li¹  Zong-Ze Zhang²  Derek J. McPhee³ 

[1] Department of Doppler Ultrasound, PLA421 Hospital, Guangzhou 510318, China;Zhongnan Hospital of Wuhan University, Department of Anesthesiology, Wuhan University, Wuhan 430071, China;;Zhongnan Hospital of Wuhan University, Department of Anesthesiology, Wuhan University, Wuhan 430071, China

关键词: synthesis;    imidazoles;    local anesthetic agent;   

DOI  :  10.3390/molecules201119696

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.