RESUMO
Influenza virus infection constitutes a significant health problem in need of more effective therapies. We have recently identified ((2R,3S,4R,5R)-3-acetoxy-5-(4-benzamido-2-oxopyrimidin-1(2H)-yl)-4-fluoro-3,4-dimethyl-tetrahydrofuran-2-yl) methyl benzoate (18c) as a potent influenza virus inhibitor. We now here report the synthesis and evaluation of a series of C-3' modified ribose nucleosides. These novel compounds were prepared, primarily by taking known ((2R,3R,4R)-3-benzoyloxy-4-fluoro-4-methyl-5-oxo-tetrahydrofuran-2-yl)methyl benzoate (1) and converting it in to C-3 keto sugar (7), reacting C-3 keto group with methyl magnesium bromide, followed by coupling these sugars with purine and pyrimidine bases. Anti influenza viral activity was determined by screening against both A and B viral strains.
Assuntos
Antivirais/síntese química , Nucleosídeos de Purina/química , Nucleosídeos de Purina/farmacologia , Nucleosídeos de Pirimidina/síntese química , Nucleosídeos de Pirimidina/farmacologia , Animais , Antivirais/farmacologia , Linhagem Celular , Cães , Humanos , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza B/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Relação Estrutura-AtividadeRESUMO
New styryl sulfone compounds have been synthesized and evaluated for their anti-proliferative activity. Among the compounds synthesized, one compound (7k) has shown 51% tumor growth inhibition in mice implanted with HT-29 human carcinoma at 400 mg kg(-1) orally.
Assuntos
Antineoplásicos/farmacologia , Sulfonas/farmacologia , Animais , Antineoplásicos/síntese química , Divisão Celular/efeitos dos fármacos , Células HT29 , Humanos , Camundongos , Camundongos Nus , Estrutura Molecular , Sulfonas/síntese química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
New 3-O-substituted benzyl pyridazinone compounds have been synthesised and evaluated for their cyclooxygenase inhibitory activity and COX-2 selectivity. Among the compounds synthesised, three compounds (11b-11d) have shown in vitro COX-2 selectivity. These compounds have been evaluated for their in vivo potential using carrageenan-induced rat paw edema assay. One compound (11b) showed 32% anti-inflammatory activity at 30 mgkg(-1) dose.
