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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Discovery of (R)-6-cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-3-((5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl)-4-hydroxy-5,6-dihydropyran-2-one (PF-00868554) as a potent and orally available hepatitis C virus polymerase inhibitor.

The HCV RNA-dependent RNA polymerase has emerged as one of the key targets for novel anti-HCV therapy development. Herein, we report the optimization of the dihydropyrone series inhibitors to improve compound aqueous solubility and reduce CYP2D6 inhibition, which led to the discovery of compound 24 (PF-00868554). Compound 24 is a potent and selective HCV polymerase inhibitor with a favorable pharmacokinetic profile and has recently entered a phase II clinical evaluation in patients with genotype 1 HCV.[1]

References

  1. Discovery of (R)-6-cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-3-((5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl)-4-hydroxy-5,6-dihydropyran-2-one (PF-00868554) as a potent and orally available hepatitis C virus polymerase inhibitor. Li, H., Tatlock, J., Linton, A., Gonzalez, J., Jewell, T., Patel, L., Ludlum, S., Drowns, M., Rahavendran, S.V., Skor, H., Hunter, R., Shi, S.T., Herlihy, K.J., Parge, H., Hickey, M., Yu, X., Chau, F., Nonomiya, J., Lewis, C. J. Med. Chem. (2009) [Pubmed]
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