Nitroaromatic amino acids as inhibitors of neuronal nitric oxide synthase

被引：30

作者：

Cowart, M ^{[1
]}

Kowaluk, EA ^{[1
]}

Daanen, JF ^{[1
]}

Kohlhaas, KL ^{[1
]}

Alexander, KM ^{[1
]}

Wagenaar, FL ^{[1
]}

Kerwin, JF ^{[1
]}

机构：

[1] Abbott Labs, Div Pharmaceut Prod, Neurol & Urol Dis Res, Abbott Pk, IL 60064 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1998年 / 41卷 / 14期

关键词：

D O I：

10.1021/jm980073h

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Nitric oxide (NO .) is an important biomodulator of many physiological processes. The inhibition of inappropriate production of NO . by the isoforms of nitric oxide synthase (NOS) has been proposed as a therapeutic approach for the treatment of stroke, inflammation, and other processes. In this study, certain 2-nitroaryl-substituted amino acid analogues were discovered to inhibit NOS. Analogues bearing a 5-methyl substituent on the aromatic ring demonstrated maximal inhibitory potency. For two selected inhibitors, investigation of the kinetics of the enzyme showed the inhibition to be competitive with L-arginine. Additionally, functional NOS inhibition in tissue preparations was demonstrated.

引用

页码：2636 / 2642

页数：7

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