ABSTRACT
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.
Subject(s)
Antiviral Agents/chemical synthesis , Purine Nucleosides/chemistry , Purine Nucleosides/pharmacology , Pyrimidine Nucleosides/chemical synthesis , Pyrimidine Nucleosides/pharmacology , Animals , Antiviral Agents/pharmacology , Cell Line , Dogs , Humans , Influenza A virus/drug effects , Influenza B virus/drug effects , Influenza, Human/drug therapy , Influenza, Human/virology , Structure-Activity RelationshipABSTRACT
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.
Subject(s)
Antineoplastic Agents/pharmacology , Sulfones/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Cell Division/drug effects , HT29 Cells , Humans , Mice , Mice, Nude , Molecular Structure , Sulfones/chemical synthesis , Xenograft Model Antitumor AssaysABSTRACT
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.
