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

Castano, Tania; Encinas, Arantxa; Perez, Concepcion; Castro Ana; Campillo, Nuria E.; Gil, Carmen

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. (C) 2008 Elsevier Ltd. All rights reserved.

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Título según WOS: ID WOS:000256378200037 Not found in local WOS DB
Título de la Revista: BIOORGANIC & MEDICINAL CHEMISTRY
Volumen: 16
Número: 11
Editorial: PERGAMON-ELSEVIER SCIENCE LTD
Fecha de publicación: 2008
Página de inicio: 6193
Página final: 6206
DOI:

10.1016/j.bmc.2008.04.036

Notas: ISI