Síntese de novos derivados 1h-pirazolo[3,4-b]piridina fosforamidatos candidatos a atividade antileishmania

• Ano de defesa: 2011
• Autor(a) principal: Furtado, Antonia Carlene Rodrigues
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Programa de Pós-graduação em Química; Química
• Palavras-chave em Português: Pirazolopiridina; Derivados; Leishmania; Síntese orgânica; Fosforamidato; Síntes orgânica; Aminoalquilfosforamidato; Pyrazolopyridine; Derivatives; Organic synthesis; Phosphoramidate; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
• Link de acesso: https://app.uff.br/riuff/handle/1/20703

The leishmaniases are zoonoses considered initially broadcast essentially wild, being limited to rural areas and small urban areas. Currently shows changes in transmission patterns due to the socio-environmental changes such as deforestation and the migration process characterized by the rural exodus, taking the man to the outskirts of large cities. Its dynamics is different between the sites of occurrence as a function of variables related to parasites, vectors, ecosystems and social processes of production of land use. The search for new drugs that have both antileishmanial activity and low toxicity has stimulated the interest of the scientific community. Aiming to contribute to the treatment of this neglected disease, this work presents the synthesis of 15 new compounds X-(1H-pyrazolo[3,4-b] pyridine-4-ylamino alkylphosphoramidate of diisopropyl 73a-e, 74a-e and 75a-e possessing different substituents on the heterocyclic system and methylene spacers of increasing size. Derivatives 73, 74 and 75 were obtained with yields between 67-83% by nucleophilic aromatic substitution reaction of chlorine atom present in position -4 of substrates 1H-pyrazolo[3,4-b]pyridine 64, 68 and 72 promoted by the terminal amino group of 29a-e. There was no appreciable difference in earnings the change in the size of the alkylene chain, but it is suggested that the lowest income found in 75 series over the series 73 and 74 due to issues caused by steric R = phenyl group at position 3 heterocyclic ring.Intermediaries 1H pyrazolo[3,4-b]pyridine 64, 68 and 72 were obtained with yields ranging from 62-75% for the conversion of 5 aminopyrazoles replaced the corresponding acrylates, followed by reaction with chlorocyclization dowtherm and POCl3. The aminoalkylphosphoramidate 29a-e were obtained from direct reaction of diamines with monofosforilação of diisopropyl phosphonate 25 in yields between 50-53%. The evaluation of antileishmanial activity of 15 new compounds with the promastigotes of Leishmania amazonensis is in progress.