FLEXIBLE N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE ANALOGS - SYNTHESIS AND MONOAMINE-OXIDASE CATALYZED BIOACTIVATION

被引：38

作者：

EFANGE, SMN ^{[1
]}

MICHELSON, RH ^{[1
]}

REMMEL, RP ^{[1
]}

BOUDREAU, RJ ^{[1
]}

DUTTA, AK ^{[1
]}

FRESHLER, A ^{[1
]}

机构：

[1] UNIV MINNESOTA,DEPT MED CHEM,MINNEAPOLIS,MN 55455

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 33卷 / 12期

关键词：

D O I：

10.1021/jm00174a007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Eighteen analogues of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and evaluated as substrates of monoamine oxidase. In general, the flexible analogues, characterized by the presence of a methylene (or ethylene) bridge between the aryl/heteroaryl and tetrahydropyridyl moieties, were better substrates of the enzyme than the conformationally restricted MPTP. It is suggested that the increased oxidative activity of these flexible analogues reflects enhanced binding due to the ability of the C-4-aryl/heteroaryl substituent to gain access to a hydrophobic pocket within the substrate binding site. © 1990, American Chemical Society. All rights reserved.

引用

页码：3133 / 3138

页数：6

共 27 条

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