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  • Title: Nitroaromatic amino acids as inhibitors of neuronal nitric oxide synthase.
    Author: Cowart M, Kowaluk EA, Daanen JF, Kohlhaas KL, Alexander KM, Wagenaar FL, Kerwin JF.
    Journal: J Med Chem; 1998 Jul 02; 41(14):2636-42. PubMed ID: 9651169.
    Abstract:
    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.
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