Substituted N-Phenylisothioureas: Potent Inhibitors of Human Nitric Oxide Synthase with Neuronal Isoform Selectivity
| Autor: | Barry G. Shearer, Edward P. Garvey, Jeffrey Alan Oplinger, Lloyd Frick, Furfine Eric Steven, Shuliang Lee |
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| Rok vydání: | 1997 |
| Předmět: |
Gene isoform
Stereochemistry Arginine Binding Competitive Isozyme Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Animals Humans Structure–activity relationship Enzyme Inhibitors Neurons chemistry.chemical_classification Trifluoromethyl Molecular Structure biology Thiourea Brain Rats Isoenzymes Nitric oxide synthase Enzyme Biochemistry chemistry Enzyme inhibitor biology.protein Citrulline Molecular Medicine Nitric Oxide Synthase Selectivity |
| Zdroj: | Journal of Medicinal Chemistry. 40:1901-1905 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | S-Ethyl N-phenylisothiourea (4) has been found to be a potent inhibitor of both the human constitutive and inducible isoforms of nitric oxide synthase. A series of substituted N-phenylisothiourea analogues was synthesized to investigate the structure-activity relationship of this class of inhibitor. Each analogue was evaluated for human isoform selectivity. One analogue, S-ethyl N-[4-(trifluoromethyl)phenyl]isothiourea (39), exhibited 115-fold and 29-fold selectivity for the neuronal isoform versus the inducible and endothelial derived constitutive isoforms, respectively. Studies have shown the substituted N-phenylisothiourea 39 binds competitively with L-arginine. |
| Databáze: | OpenAIRE |
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