Journal of Medicinal Chemistry p. 705 - 716 (1992)
Update date:2022-08-02
Topics: Sulfonamides
Ellingboe, John W.
Spinelli, Walter
Winkley, Michael W.
Nguyen, Thomas T.
Parsons, Roderick W.
et al.
The synthesis and Class III antiarrhythmic activity of a series of 4-<(methylsulfonyl)amino>benzamides and sulfonamides are described.Selected compounds shown a potent Class III activity and are devoid of effects on conduction both in vitro (dog Purkinje fibers) and in vivo (anesthetized dogs).Compounds having a 2-aminobenzimidazole group were found to be the most potent, and one compound having the heterocycle (5, WAY-123,398) was selected for further characterization.Compound 5 was shown to have good oral bioavailability and a favorable hemodynamic profile to produce a 3-fold increase of the ventricular fibrillation threshold and to terminate ventricular fibrillation, restoring sinus rhythm in anesthetized dogs.Voltage-clamp studies in isolated myocytes show that 5 is a potent and specific blocker of the delayed rectifier potassium current (IK) at concentrations that cause significant prolongation of action potential duration.
View MoreHebei Kangtai Pharmaceutical Co.,Ltd
Contact:+86-0317-3512963
Address:Wugang Road,Mengcun of Cangzhou City,Hebei Province ,China
Beijing Stable Chemcial Co.ltd
Contact:86-10-63785052
Address:A1301 Technological Edifice. No.4 FuFeng Road,FengTai District, Beijing. China
Contact:18669908765
Address:Zibo City, Shandong Province, P.R.China
Contact:+86-25-52346955
Address:199,JIANYE ROAD,NANJING,CHINA
Nanjing Chemlin Chemical Co., Ltd.
website:http://www.echemlin.cn
Contact:+86-25-83697070
Address:Rm.902 Longyin Plaza, No. 217 Zhongshan Rd.(N) Nanjing 210009,China
Doi:10.1134/S0022476618050244
(2018)Doi:10.1039/P29910001649
(1991)Doi:10.1016/j.jorganchem.2012.04.023
(2012)Doi:10.1039/c2cc32731g
(2012)Doi:10.1002/ejoc.201901206
(2019)Doi:10.1246/bcsj.66.3760
(1993)