Síntese e avaliação farmacológica de novos aciclonucleosídeos quinolônicos como potenciais antivirais e tuberculostáticos

• Ano de defesa: 2006
• Autor(a) principal: Santos, Fernanda da Costa
• Orientador(a): Souza, Maria Cecília Bastos Vieira de
• Banca de defesa: Echevarria, Aurea , Ferreira, Vítor Francisco , Bernardino, Alice Maria Rolim , Alves, Thatyana Rocha
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Programa de Pós-Graduação: Programa de Pós-graduação em Química Orgânica
• Departamento: Química Orgânica
• Palavras-chave em Português: Aciclonucleosídeos; Quinolonas; Antivirais; Tuberculásticos; Síntese orgânica
• Área do conhecimento CNPq: CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA
• Link de acesso: https://app.uff.br/riuff/handle/1/21074

In this work 10 (ten) new compounds were synthesized. 3-carbethoxy-4-oxo-1,4-dihydroquinolines 53a-d and 4-oxo-1,4-dihydroquinoline-3-carboxybenzylamides 52a-d were obtained in 83-95% yields. Acyclonucleosides 1-[(2-hydroxiethoxy)methyl]-3-carbethoxy-4-oxo-1,4-dihydroquinolines 58a-d and 1-[(2-hydroxiethoxy)methyl]-4-oxo-1,4-dihydroquinoline-3-carboxybenzilamides 49a-b and 49d were synthesizede employing a one pot reaction: silylation of the desired quinolone (BSTFA, 1% CTMS) followed by equimolar amount addition of 1,3-dioxolane, chlorotrimethylsilane and KI, at room temperature. These substances were obtained in 52-96% yields. New quinolone acyclonucleosides with potential biological activity, 1-[(2-hydroxiethoxy)methyl]-4-oxo-1,4-dihydroquinoline-3-carbohydrazides 50a-d, were prepared in 55-75% yields by nucleofilic substitution reaction between of the 1-[(2-hydroxiethoxy)methyl]-3-carbethoxy-4-oxo-1,4dihydroquinolines 58a-d and hidrazine. The acyclonucleosides 50b and 50d were reacted with 4-chlorobenzaldehyde under acid catalysis, leading to the corresponding acylhidrazones 51b and 51d, in 95 and 90% yields, respectively. The structures of the new compounds are supported by spectrostopic analysis. Antiviral or tuberculostatic activity of some of the new quinolone acyclonucleosides 49, 50 and 51 was evaluated.