Diseño, Síntesis y Evaluación Biológica de Derivados Carboxamídicos e Imidamídicos como Inhibidores de Óxido Nítrico Sintasa

Abstract

The main goal of this doctoral thesis is the design, synthesis and biological evaluation of new carboxamidic and imidamidic derivatives as inhibitors for the different NOS isoforms. By this means, we are able to contribute developing potent and selective compounds to target NO overproduction in potential drugs for the diseases where is involved. The specific objectives necessaries for this purpose are: I. Following the path of previous articles from our research group, design new compounds blending together the characteristics which proportionate the highest selectivity and the most potent inhibition in each NOS isoform. II. Incorporate amidine and guanidine substructures, proven in bibliography to be great moieties for NOS inhibition, to our own molecules. III. Develop a synthetic strategy that will allow obtaining the final products with the highest yield possible. IV. Purification and characterization of any new molecule synthesized by nuclear magnetic resonance studies (NMR) and high resolution mass spectrometry (HRMS). V. Biological activity determination for the neuronal and inducible NOS isoforms in all the final products, and in the endothelial one on those with the best inhibition values. VI. Analyze how the structural modifications influence on the potency and selectivity of the inhibitors.