Stereospecific synthesis of "para-hydroxymexiletine" and sodium channel blocking activity evaluation
Stereospecific synthesis of "para-hydroxymexiletine" and sodium channel blocking activity evaluation
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DOI：
10.1002/chir.10307
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发表时间：
2004-02-01
期刊：
影响因子：
2
通讯作者：
Camerino, DC
中科院分区：
文献类型：
--
作者：
Catalano, A;Carocci, A;Camerino, DC
合成了美西律的主要代谢产物之一“对羟基美西律”（PHM）的两种对映体，并对其进行了充分表征。评价了（R）-和（S）-PHM在对蛙骨骼肌Na+通道的阻断效力和立体选择性方面的性质。在4-位芳氧基部分上存在羟基，如在PHM中，相对于美西律降低I-Na（max）的效力降低。然而，PHM表现出明显的使用依赖性行为类似于美西律，并与观察到的母体化合物相比，在使用依赖性阻滞期间保持其立体选择性。(C)2004Wiley-Liss，Inc.
Both enantiomers of "para-hydroxymexiletine" (PHM), one of the main metabolites of mexiletine, were synthesized and fully characterized. Properties of (R)- and (S)-PHM, in terms of blocking potency and stereoselectivity on frog skeletal muscle Na+ channels, were evaluated. The presence of a hydroxy group on the aryloxy moiety in the 4-position, as in PHM, reduced potency with respect to mexiletine in reducing I-Na (max). However, PHM showed clear use-dependent behavior similar to that of mexiletine and, in contrast with what is observed with the parent compound, maintained its stereoselectivity during the use-dependent block. (C) 2004Wiley-Liss, Inc.