【文章名】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-o ne (PF-00868554) as a Potent and Orally Available Hepatitis C Virus Polymerase Inhibitor.
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-o ne (PF-00868554) as a Potent and Orally Available Hepatitis C Virus Polymerase Inhibitor.
[摘要]：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 compd. aq. soly. and reduce CYP2D6 inhibition, which led to the discovery of compd. 24 (PF-00868554)(I). Compd. 24 is a potent and selective HCV polymerase inhibitor with a favorable pharmacokinetic profile and has recently entered a phase II clin. evaluation in patients with genotype 1 HCV.
