Síntese e avaliação do potencial leishmanicida e tripanocida de 1,6-naftiridinas substituídas

by Schwartz, Melissa Geórgia

Abstract (Summary)
The trypanosomiasis and the leishmaniasis are serious problems of public health affecting millions of people in the country and worldwide. The majority of the drugsused in the treatment of these diseases was developed many decades ago, and present little efficacy and intense collateral effects. The biologycal importance of the naphthyridines and the interest in discovering new leishmanicides and trypanocides agents has stimulated the synthesis of 1,6-naphthyridine-4-substituted and the evaluation of its leishmanicidal and trypanocidal potential. The methodology used for the preparation of 4-(4´-diethylamino-1´-methylbutylamino)-1,6-naphthyridine involves the methoxymethylene derivative of Meldrum´s acid that has been widely used as precursor of a variety of the heterocyclic cores. The adduct of Meldrum´s acid is easily obtained by the reaction of Meldrum´s acid and trimethyl orthoformate with the 4-amino-pyridine. The thermal cyclization of this adduct in diphenyl ether supplies 1,6-naphthyridine-4-(1H)-one, that after chlorination with POCl3 results in 4-chloro-1,6-naphthyridine. The conversion of this compound in the aminonaphthyridine happens through a reaction of nucleophilic substitution with the 2-amino-5-diethylamino-pentane. This reaction was repeated many times, presenting difficultiesin the purification of the product and low yields, thus it needs better reaction conditions. The obtained compounds were characterized by spectroscopic techniques of IR, 1H NMR and 13C NMR. The evaluation of the leishmanicidal andtrypanocidal properties was made for the compound 4-chloro-1,6-naphthyridine, however it presented no activity
This document abstract is also available in Portuguese.
Bibliographical Information:

Advisor:Ricardo Andrade Rebelo; Angela Malheiros; Flávia Aparecida Fernandes da Rosa; Iêda Maria Begnini

School:Universidade Regional de Blumenau

School Location:Brazil

Source Type:Master's Thesis

Keywords:1,6-naftiridinassubstituídas synthesis substituted 1,6-naphthyridines


Date of Publication:02/10/2006

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