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 4. Optimization of DMPK properties
- Resource Type
- Article
- Authors
- Sergeeva, Maria V.; Zhou, Yuefen; Bartkowski, Darian M.; Nolan, Thomas G.; Norris, Daniel A.; Okamoto, Ellen; Kirkovsky, Leo; Kamran, Ruhi; LeBrun, Laurie A.; Tsan, Mei; Patel, Rupal; Shah, Amit M.; Lardy, Matthew; Gobbi, Alberto; Li, Lian-Sheng; Zhao, Jingjing; Bertolini, Thomas; Stankovic, Nebojsa; Sun, Zhongxiang; Murphy, Douglas E.
- Source
- Bioorganic & Medicinal Chemistry Letters. Jun2008, Vol. 18 Issue 11, p3421-3426. 6p.
- Subject
- *PYRIDAZINONES
*HEPATITIS C virus
*DRUG metabolism
*PHARMACOKINETICS
- Language
- ISSN
- 0960-894X
Abstract: 5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as potent inhibitors of genotype 1 HCV NS5B polymerase focusing on the optimization of their drug metabolism and pharmacokinetics (DMPK) profiles. This investigation led to the discovery of potent inhibitors with improved DMPK properties. [Copyright &y& Elsevier]