Structure-based design, synthesis, and biological evaluation of 1,1-dioxoisothiazole and benzo[b]thiophene-1,1-dioxide derivatives as novel inhibitors of hepatitis C virus NS5B polymerase
Journal Article
·
· Bioorg. Med. Chem. Lett.
A novel series of HCV NS5B polymerase inhibitors comprising 1,1-dioxoisothiazoles and benzo[b]thiophene-1,1-dioxides were designed, synthesized, and evaluated. SAR studies guided by structure-based design led to the identification of a number of potent NS5B inhibitors with nanomolar IC{sub 50} values. The most potent compound exhibited IC{sub 50} less than 10 nM against the genotype 1b HCV polymerase and EC{sub 50} of 70 nM against a genotype 1b replicon in cell culture. The DMPK properties of selected compounds were also evaluated.
- Research Organization:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1006738
- Journal Information:
- Bioorg. Med. Chem. Lett., Journal Name: Bioorg. Med. Chem. Lett. Journal Issue: (14) ; 07, 2008 Vol. 18; ISSN 0960-894X
- Country of Publication:
- United States
- Language:
- ENGLISH
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