Stock B, Spiteller G
Arzneimittelforschung. 1979;29(4):610-5.
The investigation of the metabolism of the antiparkinson drugs trihexyphenidyl (1), pridinol (2) and biperiden (3) revealed a graduate tendency for hydroxylation in the different structural elements: If alicyclic, saturated heterocyclic and aromatic ring systems are present in one compound like in 1, the alicyclic ring system is attacked predominately. The amount of metabolites with hydroxy-groups in the saturated heterocyclic ring is much lower, and no hydroxylation takes place in the aromatic ring. In drugs without alicyclic ring systems like 2 the saturated heterocyclus is attacked preferentially, but also some phenolic metabolites are formed. Consequently the following arrangement of falling hydroxylation-tendency can be established: Formula: see text. Probably this arrangement is of common validity and therefore a prediction on the hydroxylation-tendency of other compounds seems to be possible.
对抗帕金森药物苯海索(1)、丙环定(2)和安克痉(3)的代谢研究表明,在不同结构单元中存在羟基化的逐渐趋势:如果一种化合物中存在脂环族、饱和杂环和芳环系统,如在1中,脂环族环系统主要受到攻击。饱和杂环中带有羟基的代谢物数量要低得多,芳环中不发生羟基化。在没有脂环族环系统的药物中,如2,饱和杂环优先受到攻击,但也会形成一些酚类代谢物。因此,可以确定以下羟基化趋势降低的排列顺序:公式:见原文。可能这种排列具有普遍有效性,因此对其他化合物的羟基化趋势进行预测似乎是可能的。