Síntesis one pot del antiinflamatorio naproxeno y evaluación in-silico de nuevos candidatos a fármaco aines

Abstract

In the synthesis of the anti-inflammatory Naproxen, the asymmetric synthesis and separation of racemates have been studied for several years in order to achieve higher yields, reduce costs and waste products of the previous methodologies. This is why, in this work, a synthetic ONE POT methodology is studied, in order to achieve the same objectives. The procedure consists of the synthesis of 2-chloro-1-propanol and 2-methoxynaphthalene, 2 precursors that, with their subsequent alkylation and oxidation, are expected to synthesize 2- (6-methoxynaphthalen-2-yl) propanoic acid or (Naproxen). Once the syntheses have been carried out, infrared spectroscopy analysis is carried out in each of the steps to confirm the success of each step. Where the presence of the relevant bands are found to indicate the final success of the synthesis, however, it is recommended to perform nuclear magnetic resonance analysis of hydrogen and carbon in order to corroborate it. On the other hand, the current non-steroidal anti-inflammatory drugs (NSAIDs) that are on the market have the great disadvantage of presenting gastrointestinal insults, liver failure and cardiovascular effects. Consequently, the computational study of new drugs based on analogous structures and showing high affinities for the enzymes that interact in these processes are important in pharmacological advancement. Thus, the design of 40 structures based on the naproxen pharmacophore is carried out together with functional groups such as; sulfonyls, sulfonates, sulfonamides, amides and the addition of a wide variety of 5 and 6 membered heterocycles such as; pyrroles, pyrazoles, thiazoles, oxazoles, oxadiazoles, imidazoles and some series of pyridines. The computational analysis of the ligand-enzyme coupling was carried out using the AutoDock Vina program and the AutoDock Tools graphical interface.