Síntesis y evaluación de heteroariliden-3,5-dihidroimidazolonas y 4H-oxazolonas como inhibidores de calpaína
- Autores: María Morón Galán
- Directores de la Tesis: Juan J. Vaquero López (dir. tes.), Carolina Burgos García (codir. tes.)
- Lectura: En la Universidad de Alcalá ( España ) en 2012
- Idioma: español
- Tribunal Calificador de la Tesis: Julio Álvarez-Builla Gómez (presid.), Manuel Rodríguez Puyol (secret.), Bernardo Herradón García (voc.), María del Pilar Cabildo Miranda (voc.), Jesus Ezquerra Carrera (voc.)
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- Resumen
The calpain family is a group of cysteine proteases unique in their dependency on calcium to attain functionally active forms. Calpains are involved in a wide range of cellular calcium-regulated functions. Moreover, altered calpain activity has been observed in several human diseases. Therefore, the design and synthesis of calpain inhibitors remains an important area of research directed at the development of new pharmaceuticals. In this context, this Thesis has focused on the design and synthesis of new calpain inhibitors, as the main purpose. Firstly, we envisaged the pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine system and other related azolopyrimidines could be of interest as new heterocyclic templates in the development of new calpain inhibitors, several series of new azolopyrimidine-peptide hibrids prepared were inactive as calpain inhibitors. In the course of this work, the reaction of methyl-5-bromo-pyrido[3¿,2¿: 4,5]pyrrolo[1, 2-c]pyrimidine-7-carboxilate with of 2-methoxyethylamine afforded 3-(2-metoxietil)-5-[(2-metoxietilamino)-(1H-pirrolo[2,3-b]piridin-2-il)-metilen]-3,5-dihidroimidazol-4-ona.This unexpective azaindole derivative showed good activity as calpain inhibitor. Consequently we focused our work on a structure-activity relationship (SAR) study on this compound. We selected 3 domains to achieve structural diversity. This study generated around 60 analogs, eight of them showed really good activity as calpain inhibitor.
