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Substituted benzothiadizine inhibitors of Hepatitis C virus polymerase. | LitMetric
The synthesis and optimisation of HCV NS5B polymerase inhibitors with improved potency versus the existing compound 1 is described. Substitution in the benzothiadiazine portion of the molecule, furnishing improvement in potency in the high protein Replicon assay, is highlighted, culminating in the discovery of 12h, a highly potent oxyacetamide derivative.
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Collegeville , PA 19426, USA.
The synthesis and optimisation of HCV NS5B polymerase inhibitors with improved potency versus the existing compound 1 is described. Substitution in the benzothiadiazine portion of the molecule, furnishing improvement in potency in the high protein Replicon assay, is highlighted, culminating in the discovery of 12h, a highly potent oxyacetamide derivative.
A series of 4-propylderivatives of 2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c] [1,2,4]benzothiadizine-5,5-dioxide substituted or unsubstituted in the benzene ring was synthesized. Derivatives of these compounds together with those of the corresponding 4-methyl and 4-ethyl derivatives prepared previously were tested for cardiovascular effects in the anesthesized rat. All the compounds studied showed hypotensive activity which was particularly intense for compounds (X), (XIX), (XXII), (XXV), and produced an increase in differential pressure marked for (XXV) and (XXVIII) which was often accompanied by pronounced bradycardia (XVII), (XVIII) and (XIX).
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