943779-01-9Relevant academic research and scientific papers
Discovery of pyrido[2,3-d]pyrimidine-based inhibitors of HCV NS5A
Degoey, David A.,Betebenner, David A.,Grampovnik, David J.,Liu, Dachun,Pratt, John K.,Tufano, Michael D.,He, Wenping,Krishnan, Preethi,Pilot-Matias, Tami J.,Marsh, Kennan C.,Molla, Akhteruzzaman,Kempf, Dale J.,Maring, Clarence J.
, p. 3627 - 3630 (2013/07/19)
Efforts to improve the genotype 1a potency and pharmacokinetics of earlier naphthyridine-based HCV NS5A inhibitors resulted in the discovery of a novel series of pyrido[2,3-d]pyrimidine compounds, which displayed potent inhibition of HCV genotypes 1a and 1b in the replicon assay. SAR in this system revealed that the introduction of amides bearing an additional 'E' ring provided compounds with improved potency and pharmacokinetics. Introduction of a chiral center on the amide portion resulted in the observation of a stereochemical dependence for replicon potency and provided a site for the attachment of functional groups useful for improving the solubility of the series. Compound 21 was selected for administration in an HCV-infected chimpanzee. Observation of a robust viral load decline provided positive proof of concept for inhibition of HCV replication in vivo for the compound series.
ANTI-VIRAL COMPOUNDS
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, (2008/12/08)
Compounds effective in inhibiting replication of Hepatitis C virus ( HCV ) or other viruses are disclosed. This invention is also directed to compositions comprising such compounds, coformulation or co-administration of such compounds with other anti-viral or therapeutic agents, processes and intermediates for the syntheses of such compounds, and methods of using such compounds for the treatment of HCV or other viral infections.
