Substituted N-Phenylisothioureas: Potent Inhibitors of Human Nitric Oxide Synthase with Neuronal Isoform Selectivity
- 1 June 1997
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 40 (12), 1901-1905
- https://doi.org/10.1021/jm960785c
Abstract
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.Keywords
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