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对羟基[双(邻吗啉基甲基)]苯基-1,4-DHP 化合物的抗高血压和抗心律失常性质:与同类其他化合物的比较及与 logP 值的关系。

Antihypertensive and antiarrhythmic properties of a para-hydroxy[bis(ortho-morpholinylmethyl)]phenyl-1,4-DHP compound: comparison with other compounds of the same kind and relationship with logP values.

机构信息

Universidad Nacional Autónoma de México, FES-Cuautitlán, Laboratorio de Química Medicinal, Campo 1. Av. 1ero de mayo S/N. 54714 Estado de México, México.

出版信息

Eur J Med Chem. 2010 Oct;45(10):4622-30. doi: 10.1016/j.ejmech.2010.07.027. Epub 2010 Jul 23.

Abstract

A new para-hydroxy[bis(ortho-morpholinylmethyl)]phenyl-1,4-DHP substituted compound, (4-(4-hydroxy-3,5-bis(morpholin-4-ylmethyl)phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester, LQM300), with antihypertensive and antiarrhythmic properties, has been synthesized. Four pKa values of this compound have been determined with the aid of the program SQUAD, at pseudo-physiological conditions (T = 37 degrees C and I = 0.15 M) by UV spectrophotometry and at T = 25 degrees C and I = 0.05 M by Capillary Zone Electrophoresis (CZE). The logP = 2.7 +/- 0.2 between n-octanol and water, has been estimated by UV spectrophotometry. The antihypertensive and antiarrhythmic efficacies as well as the logP values have been compared with other compounds of the same kind and related with their structure.

摘要

一种新的对-羟基[双(邻-吗啉基甲基)]苯基-1,4-DHP 取代化合物,(4-(4-羟基-3,5-双(吗啉-4-基甲基)苯基)-2,6-二甲基-1,4-二氢吡啶-3,5-二羧酸二乙酯,LQM300),具有抗高血压和抗心律失常的特性,已经被合成。该化合物的四个 pKa 值已经在程序 SQUAD 的帮助下确定,在假生理条件(T = 37 摄氏度,I = 0.15 M)下通过紫外分光光度法和在 T = 25 摄氏度,I = 0.05 M 下通过毛细管区带电泳(CZE)。通过紫外分光光度法估计的正辛醇和水之间的 logP = 2.7 +/- 0.2。已经将抗高血压和抗心律失常的疗效以及 logP 值与其他同类化合物进行了比较,并与它们的结构相关联。

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