Bisubstrate inhibitors of the enzyme catechol O-methyltransferase (COMT):: Efficient inhibition despite the lack of a nitro group

被引：30

作者：

Paulini, R

Lerner, C

Jakob-Roetne, R

Zürcher, G

Borroni, E

Diederich, F ^{[1
]}

机构：

[1] ETH Honggerberg, HCI, Organ Chem Lab, CH-8093 Zurich, Switzerland

[2] Hoffmann La Roche AG, Praklin Forsch, Pharma Div, CH-4070 Basel, Switzerland

来源：

CHEMBIOCHEM | 2004年 / 5卷 / 09期

关键词：

bisubstrate inhibitors; medicinal chemistry; structure-activity relationships; structure-based design transferases;

D O I：

10.1002/cbic.200400084

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A new generation of bisubstrate inhibitors for the S-adenosylmethionine- and magnesium ion-dependent enzyme catechol O-methyltransferase (COMT), feature binding affinities (IC50 values) in the double-digit nanomolar range despite the lack of a nitro group on the catechol moiety. Inhibitor potency does not directly correlate with the pKa value of the catechol HO groups and is strongly enhanced by hydrophobic aromatic substituents attached in a biaryl-type fashion to position 5 of the catechol ring.

引用

页码：1270 / 1274

页数：5

共 45 条

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