3e51

Publication Abstract from PubMed

The synthesis of 4-(1',1'-dioxo-1',4'-dihydro-1'lambda(6)-benzo[1',2',4']thiadiazin-3'-yl)- 5-hydroxy-2H-pyridazin-3-ones bearing 6-amino substituents as potent inhibitors of the HCV RNA-dependent RNA polymerase (NS5B) is described. Several of these agents also display potent antiviral activity in cell culture experiments (EC(50)<0.10 microM). In vitro DMPK data (microsome t(1/2), Caco-2 P(app)) for many of the compounds are also disclosed, and a crystal structure of a representative inhibitor complexed with the NS5B protein is discussed.

Novel HCV NS5B polymerase inhibitors derived from 4-(1',1'-dioxo-1',4'-dihydro-1'lambda(6)-benzo[1',2',4']thiadiazin-3'-yl)- 5-hydroxy-2H-pyridazin-3-ones. Part 5: Exploration of pyridazinones containing 6-amino-substituents.,Dragovich PS, Blazel JK, Ellis DA, Han Q, Kamran R, Kissinger CR, LeBrun LA, Li LS, Murphy DE, Noble M, Patel RA, Ruebsam F, Sergeeva MV, Shah AM, Showalter RE, Tran CV, Tsan M, Webber SE, Kirkovsky L, Zhou Y Bioorg Med Chem Lett. 2008 Oct 15;18(20):5635-9. Epub 2008 Aug 29. PMID:18796353^[1]

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