Title of article :
Novel HCV NS5B polymerase inhibitors derived from 4-(1′,1′-dioxo-1′,4′-dihydro-1′λ6-benzo[1′,2′,4′]thiadiazin-3′-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 2: Variation of the 2- and 6-pyridazinone substituents
Author/Authors :
Yuefen Zhou، نويسنده , , Liansheng Li، نويسنده , , Peter S. Dragovich and Shella A. Fuhrman، نويسنده , , Douglas E. Murphy، نويسنده , , Chinh V. Tran، نويسنده , , Frank Ruebsam، نويسنده , , Stephen E. Webber، نويسنده , , Amit M. Shah، نويسنده , , Mei Tsan، نويسنده , , April Averill، نويسنده , , Richard E. Showalter، نويسنده , , Rupal Patel، نويسنده , , Qing Han، نويسنده , , Qiang Zhao، نويسنده , , Thomas Hermann، نويسنده , , Charles R. Kissinger، نويسنده , , Laurie LeBrun، نويسنده , , Maria V. Sergeeva، نويسنده ,
Abstract :
5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as inhibitors of genotype 1 HCV NS5B polymerase. The structure–activity relationship (SAR) associated with variation of the pyridazinone 2- and 6-substituents is discussed. The synthesis and metabolic stability of this new class of compounds are also described.
Keywords :
Pyridazinones , Hepatitis C virus (HCV) , 5-Hydroxy-3(2H)-pyridazinone derivatives , RNA-dependent RNA polymerase (RdRp) , structure-based design , Non-nucleoside NS5B inhibitors , Small molecule
