Dottorato in Scienze Farmaceutiche e Biomolecolari

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Phd thesis

Uses of the4-hydroxy-1,2,5-oxadiazole-3-yl moiety as novel bioisoster of the carboxylgroup.

Isosteric replacement of functional groups in a lead compound is a widely used approach to study receptor chemistry and to develop new drugs with optimized behaviour. When this replacement affords products with broadly similar biological properties, the groupsare called bioisosters. A number of clear bioisosteric relationships have beenestablished for many functional groups, in particular for the carboxyl group whichhas been substituted by heterocycles such as, 3-hydroxyisoxazole,3-hydroxyisothiazole and.3-hydroxy-1,2,5-thiadiazole.

The 1,2,5-oxadiazole (furazan) system and its 2-oxide (furoxan) are heterocyclic rings whose pharmacochemistry have been studying for many years. Similarly to hydroxy substituted 1,2,5-thiadiazoles, hydroxy-1,2,5-oxadiazoles are known todisplay marked acidic properties. Consequently, the4-hydroxy-1,2,5-oxadiazol-3-yl moiety could reasonably behave as a bioisoster of the carboxy function.