A quimioterapia para as leishmanioses, doenças causadas por protozoários do gênero Leishmania, ainda permanece ineficiente em diversos tratamentos. Portanto, existe a necessidade de pesquisa por novos fármacos. Nesse trabalho, foram sintetizados derivados 1-aril-1H-pirazol-4-carboximidamidas, avaliadas as atividades leishmanicida e os efeitos citotóxicos in vitro, e realizado um estudo de relação estrutura-atividade (REA) com a série de compostos. O composto 2 apresentou um perfil de atividade que pode ser melhorado através de estratégias de modificação molecular da química medicinal.Chemotherapy for leishmaniasis, diseases caused by protozoa of the genus Leishmania, remains inefficient in several treatments. So there is a need to search for new drugs. In this work, we have synthesized 1-aryl-1H-pyrazole-4-carboximidamides derivatives and evaluated antileishmanial activities in vitro, as well as cytotoxic effects. Structure-activity relationship (SAR) studies were carried out with all the compounds of the series. Compound 2 showed an activity profile that can be improved through medicinal chemistry strategies.
SummaryThree new porphyrin aminoalkyl dibenzylphosphoramidates were synthesized by nucleophilic aromatic substitution of one p-fluorine atom of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (TPPF
20) by primary aminoalkyl dibenzylphosphoramidates. The nucleophilic aromatic substitution was promoted by microwave irradiation in N-methyl-2-pyrrolidinone. Attempts to remove the benzyl groups of the phosphoramidate moiety by hydrogenolysis with 10% Pd/C led to the cleavage of the P–N bond and the reduction of the macrocycle to hydroporphyrin-type derivatives. The extent of the effect of the catalytic hydrogenation to TPPF
20 with 10% Pd/C was then studied with a variety of solvents. The results showed that ethanol/DMF is the solvent of choice to produce chlorin TPCF
20 and an ethanol/DMF/NEt3 mixture is more adequate to produce isobacteriochlorin (TPIF
20).
meso-Tetrakis(pentafluorophenyl)porphyrin reacts with aminoalkylphosphoramidates to afford porphyrins substituted with one or four phosphoramidate groups in the 4-position of the meso-aryl groups. The new porphyrin derivatives show high photostability and some are better singlet oxygen generators than meso-tetrakis(1-methylpyridinium-4-yl)porphyrin, a well known good singlet oxygen producer.
This article describes an improved method to synthesize phosphoramidic acid aminoalkyl esters from diamines by the adaptation of industrial patents. Four mono-phosphorylated products having amino sites were obtained in good a yield. Such compounds have potential coordination properties with transition metals and also potential biological activity.
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