NOVEL 4-(ARYLOXY)TETRAHYDROPYRIDINE ANALOGS OF MPTP AS MONOAMINE-OXIDASE-A AND MONOAMINE-OXIDASE-B SUBSTRATES

被引：38

作者：

KALGUTKAR, AS ^{[1
]}

CASTAGNOLI, K ^{[1
]}

HALL, A ^{[1
]}

CASTAGNOLI, N ^{[1
]}

机构：

[1] VIRGINIA POLYTECH INST & STATE UNIV, DEPT CHEM, BLACKSBURG, VA 24061 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1994年 / 37卷 / 07期

关键词：

D O I：

10.1021/jm00033a012

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The exceptionally good monoamine oxidase (MAO) substrate properties of several 4-(arylmethyl)-1-methyl-1,2,3,6-tetrahydropyridine derivatives related to the neurotoxin MPTP have prompted studies to evaluate the corresponding properties of tetrahydropyridine derivatives bearing heteroatom-linked groups at C-4. The expected dihydropyridinium metabolites generated from these MAO-A- and MAO-B-catalyzed oxidations of the 4-(aryloxy)tetrahydropyridine analogs were found to undergo rapid hydrolytic cleavage to yield the corresponding arenol and 1-methyl-2,3-dihydro-4-pyridone, a species that could be monitored spectrophotometrically. We have exploited this reaction sequence to probe the active sites of beef liver MAO-B and human placental MAO-A with a variety of 4-(aryloxy)-1-methyl-1,2,3,6-tetrahydropyridine derivatives. The results are discussed in relationship to recently published reports describing the MAO-A vs MAO-B selectivity of various 4-(arylmethyl)tetrahydropyridine derivatives.

引用

页码：944 / 949

页数：6

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