Journal of Medicinal Chemistry p. 2582 - 2595 (1995)
Update date:2022-08-03
Topics:
Estep
Josef
Bacon
Carabateas
Rumney IV
Pilling
Krafte
Volberg
Dillon
Dugrenier
Briggs
Canniff
Gorczyca
Stankus
Ezrin
Purine-based analogs of SDZ 211-500 (5) were prepared and evaluated as inactivation modifiers of guinea pig or human cardiac sodium (Na) channels expressed in Xenopus oocytes. Substances which remove or slow the Na channel inactivation process in cardiac tissue are anticipated to prolong the effective refractory period and increase inotropy and thus have potential utility as antiarrhythmic agents. Heterocyclic substitution at the 6-position of the purine ring resulted in compounds with increased Na activity and potency, with 5-membered heterocycles being optimal. Only minor modifications to the benzhydrylpiperazine side chain were tolerated. Selected compounds which delayed the inactivation of Na channels were found to increase refractoriness and contractility in a rabbit Langendorff heart model, consistent with the cellular mechanism. Activity in both the oocyte and rabbit heart assays was specific to the S enantiomers. Preliminary in vivo activity has been demonstrated following intravenous infusion. The most promising compound on the basis of in vitro data is the formylpyrrole (S)74, which is 25-fold more potent than DPI 201-106 (1) in the human heart Na channel assay.
View Morewebsite:http://www.easchem.com
Contact:+86-731-89722861 89722891
Address:2/F-4/Bld Colorful Palace, No.605 Changsha Ave, Yuhua Area Changsha Hunan China.
TIANJIN DONGRUXIANG MINERALS MARKETING CO.,LTD(expird)
Contact:22-58516360
Address:tianjin
HANGZHOU EVC CHEMICAL CO.,LTD.(expird)
Contact:+86-571-88296056
Address:Room#3001,Zhejiang Chemical Market,No.10,Road Shenban,Hangzhou,Zhejiang,China
Beijing Century Richap Chemistry Co.,Ltd
Contact:+86- 010-64455497
Address:Guannan County, Lianyungang City, Jiangsu Province, China
Tengzhou Runlong Fragrance Co., Ltd.
website:http://www.tzrunlong.com/
Contact:0086-15665710862
Address:No. 78, Fushan Road, Biomedical Industrial Park, Dawu Town, Tengzhou, Shandong, 277514 China
Doi:10.1039/DT9950002215
(1995)Doi:10.1055/s-2004-831296
(2004)Doi:10.1016/j.bmc.2006.05.006
(2006)Doi:10.1021/acs.orglett.7b02150
(2017)Doi:10.1007/BF00699142
(1994)Doi:10.1039/b405837b
(2004)