5-氟和8-氟曲美喹诺：选择性β2-肾上腺素能受体激动剂。

5-fluoro- and 8-fluorotrimetoquinol: selective beta 2-adrenoceptor agonists.

作者信息

Clark M T, Adejare A, Shams G, Feller D R, Miller D D

出版信息

J Med Chem. 1987 Jan;30(1):86-90. doi: 10.1021/jm00384a015.

DOI:10.1021/jm00384a015

Abstract

The 5-fluoro and 8-fluoro analogues of trimetoquinol, TMQ, have been synthesized and evaluated for beta 2- and beta 1-adrenoceptor activity in guinea pig trachea and atria, respectively. The fluoro analogues of TMQ maintained potent beta 2-adrenoceptor agonist activity but had reduced beta 1-adrenoceptor agonist activity. The changes in beta 1-activity of these compounds were correlated to differences in phenolic pKa's. The beta 1- and beta 2-adrenoceptor actions of 2 and 3 were blocked in a competitive manner by propranolol. The enhanced beta 2/beta 1 selectivity for the analogues was found to be 8-fluoro analogue 3 greater than 5-fluoro analogue 2 greater than trimetoquinol (1).

摘要

已合成了曲美托喹（TMQ）的5-氟和8-氟类似物，并分别在豚鼠气管和心房中对其β2和β1肾上腺素能受体活性进行了评估。TMQ的氟类似物保持了强效的β2肾上腺素能受体激动剂活性，但β1肾上腺素能受体激动剂活性有所降低。这些化合物β1活性的变化与酚类pKa的差异相关。普萘洛尔以竞争性方式阻断了2和3的β1和β2肾上腺素能受体作用。发现类似物的β2/β1选择性增强为8-氟类似物3大于5-氟类似物2大于曲美托喹（1）。

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