3h2l

Publication Abstract from PubMed

A novel series of non-nucleoside small molecules containing a tricyclic dihydropyridinone structural motif was identified as potent HCV NS5B polymerase inhibitors. Driven by structure-based design and building on our previous efforts in related series of molecules, we undertook extensive SAR studies, in which we identified a number of metabolically stable and very potent compounds in genotype 1a and 1b replicon assays. This work culminated in the discovery of several inhibitors, which combined potent in vitro antiviral activity against both 1a and 1b genotypes, metabolic stability, good oral bioavailability, and high C(12) (PO)/EC(50) ratios.

Discovery of tricyclic 5,6-dihydro-1H-pyridin-2-ones as novel, potent, and orally bioavailable inhibitors of HCV NS5B polymerase.,Ruebsam F, Murphy DE, Tran CV, Li LS, Zhao J, Dragovich PS, McGuire HM, Xiang AX, Sun Z, Ayida BK, Blazel JK, Kim SH, Zhou Y, Han Q, Kissinger CR, Webber SE, Showalter RE, Shah AM, Tsan M, Patel RA, Thompson PA, Lebrun LA, Hou HJ, Kamran R, Sergeeva MV, Bartkowski DM, Nolan TG, Norris DA, Khandurina J, Brooks J, Okamoto E, Kirkovsky L Bioorg Med Chem Lett. 2009 Nov 15;19(22):6404-12. Epub 2009 Sep 17. PMID:19818610^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.