I. Novel HCV NS5B polymerase inhibitors: Discovery of indole 2-carboxylic acids with C3-heterocycles
Journal Article
·
· Bioorg. Med. Chem. Lett.
SAR development of indole-based palm site inhibitors of HCV NS5B polymerase exemplified by initial indole lead 1 (NS5B IC{sub 50} = 0.9 {micro}M, replicon EC{sub 50} > 100 {micro}M) is described. Structure-based drug design led to the incorporation of novel heterocyclic moieties at the indole C3-position which formed a bidentate interaction with the protein backbone. SAR development resulted in leads 7q (NS5B IC{sub 50} = 0.032 {micro}M, replicon EC{sub 50} = 1.4 {micro}M) and 7r (NS5B IC{sub 50} = 0.017 {micro}M, replicon EC{sub 50} = 0.3 {micro}M) with improved enzyme and replicon activity.
- Research Organization:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- Sponsoring Organization:
- INDUSTRY
- OSTI ID:
- 1026535
- Journal Information:
- Bioorg. Med. Chem. Lett., Journal Name: Bioorg. Med. Chem. Lett. Journal Issue: (18) ; 09, 2011 Vol. 21
- Country of Publication:
- United States
- Language:
- ENGLISH
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