2. Academic Validation
  3. 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

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

  • J Med Chem. 2009 Mar 12;52(5):1255-8. doi: 10.1021/jm8014537.
Hui Li 1,  John Tatlock,  Angelica Linton,  Javier Gonzalez,  Tanya Jewell,  Leena Patel,  Sarah Ludlum,  Matthew Drowns,  Sadayappan V Rahavendran,  Heather Skor,  Robert Hunter,  Stephanie T Shi,  Koleen J Herlihy,  Hans Parge,  Michael Hickey,  Xiu Yu,  Fannie Chau,  Jim Nonomiya,  Cristina Lewis
Affiliations

Affiliation

  • 1 Pfizer Global Research and Development, La Jolla Laboratories, San Diego, California 92121, USA. hui.li@pfizer.com
PMID: 19209845 DOI: 10.1021/jm8014537
Abstract

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.

Figures