Synthesis and local anesthetic activity of fluoro-substituted imipramine and its analogues.
A series of fluoro-substituted imipramines and its analogues, 6a-6e, were synthesized and evaluated for their in vitro local anesthetic activity. Compound 6b was found to have potency, onset, and duration of action comparable to those of lidocaine (lidocaine hydrochloride, CAS:6108-05-0). Dissociation constants (pK(a)) of these compounds have been determined to be 7.6-7.9.
Li
Wen
W
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China. liwen@zzu.edu.cn <liwen@zzu.edu.cn>
You
Qidong
Q
D000779:Anesthetics, Local / Q000138:chemical synthesis; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D004594:Electrophysiology; D005461:Fluorine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007099:Imipramine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry*; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology; D008956:Models, Chemical; D009407:Nerve Block; D009474:Neurons / Q000378:metabolism; D011898:Ranidae; D012584:Sciatic Nerve / Q000378:metabolism
D000779:Anesthetics, Local; D005461:Fluorine; D008012:Lidocaine; D007099:Imipramine