Design, synthesis, and evaluation of potential inhibitors of nitric oxide synthase.

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Castano T, Encinas A, Perez C, Castro A, Campillo NE, Gil C

Design, synthesis, and evaluation of potential inhibitors of nitric oxide synthase.

Bioorg Med Chem. 2008 Jun 1;16(11):6193-206. doi: 10.1016/j.bmc.2008.04.036. Epub 2008 Apr 18.

PubMed ID

18477512 [ View in PubMed

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Abstract

Selective inhibitors of neuronal nitric oxide synthase (nNOS) were shown to protect brain and may be useful in the treatment of neurodegenerative diseases. In this context, our purpose has been to design and synthesize a new family of derivatives of thiadiazoles as possible inhibitors of nNOS. To achieve it a supervised artificial neural network model has been developed for the prediction of inhibition of Nitric Oxide Synthase using a dataset of 119 nNOS inhibitors. The definition of the molecules was achieved from a not-supervised neural network using a home made program named CODES. Also, thiadiazole-based heterocycles, previously predicted, were prepared as conformationally restricted analogues of a selective nNOS inhibitor, S-ethyl N-phenylisothiourea.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
L-N(omega)-nitroarginine-(4R)-amino-L-proline amide	Nitric oxide synthase, brain	Ki (nM)	100	N/A	N/A	Details
L-N(omega)-nitroarginine-(4R)-amino-L-proline amide	Nitric oxide synthase, brain	Ki (nM)	1100	N/A	N/A	Details
L-N(omega)-Nitroarginine-2,4-L-diaminobutyric amide	Nitric oxide synthase, brain	Ki (nM)	130	N/A	N/A	Details
Nitroarginine	Nitric oxide synthase, brain	Ki (nM)	500	N/A	N/A	Details