Síntese e caracterização estrutural de novos derivados 1-h-pirazolo[3,4-b]piridina potencialmente leishmanicidas

Abstract

Based on our previous results of a significant anti-leishmanial activity of pyrazolopyridine derivatives, new derivatives of this system were synthesized searching for a more similarly structure of anti-parasitic Amodiaquine. In this work we related the synthesis of 3 new pyrazolopyridine derivatives by synthetical approach involving the 1,3-dimethyl-5-aminopyrazole (C1) and diethyl ethoxymalonatc to afford diethyl α-carboethoxy- β-(1,3-dimethyl-5-aminopyrazolilacrilate (C2) later under POCl3 reaction fumishing the ester-pyrazolopyridine intermediate (C3). This intermediate was treated with appropriate substituted anilines and amines to afford the anilino and amino-pyrazolopyridines, respectively. The 1,3-dimethy1-4-[amino or anilino]-1H-pyrazolo[3,4-b]pyridine were obtained by two descarboxylation methods, the first startcd by the corresponding carboxylic acids at reflux in DowTherm® and, in the second method the corresponding esters were directly refluxed in concentrated phosphoric acid. The second method presented the best results for anilinopyrazolopyridine series. The hydrogen bond influence betwcen amine-nitrogen and carboxylic hydrogen, involved in descarboxylation reactions was studied by molecular modelling using the semi-empirical method AM1 (MOPAC program). The values of the reaction enthalpies showed a relationship with the experimental results, indicating the electronic effects importance of moieties in aniline ring on hydrogen bond power whose break is involved in descarboxylation reactions.