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

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.

Non-ATP competitive glycogen synthase kinase 3beta (GSK-3beta) inhibitors: study of structural requirements for thiadiazolidinone derivatives.

The 2,4-disubstituted thiadiazolidinones (TDZD) were described as the first non-ATP competitive GSK-3beta inhibitors. New modifications in this heterocyclic ring are here reported to study the influence on the biological activity. The basic skeleton of 1,2,4-thiadiazole and also one of the carbonyl groups are kept, while different modifications are introduced in positions 3 and 5, respectively.

Automated synthesis of heterocycles on solid supports.

The creation of novel diverse heterocycle libraries is an indispensable requirement of modern drug discovery processes. Currently, library sizes of over 10,000 discrete compounds are viable using programmed synthesis on solid supports. This review discusses the recent advances in the automated solid-phase syntheses of heterocycles to generate libraries of bioactive products, and illustrates library sizes that have been obtained, robots used for production of libraries, points of diversity and number of steps on the resin.

Advances in the synthesis and recent therapeutic applications of 1,2,4-thiadiazole heterocycles.

Chemical properties of 1,2,4-thiadiazole have been reviewed in the last few years. However, the usefulness of 1,2,4-thiadiazole as a privileged system in medicinal chemistry has prompted the advances on the therapeutic potential of this system. This review provides a brief summary of the medicinal chemistry of 1,2,4-thiadiazole system and highlights some examples of 1,2,4-thiadiazole-containing drug substances in the current literature.