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Discovery of PSI-353661, a Novel Purine Nucleotide Prodrug for the Treatment of HCV Infection.
- Source :
-
ACS medicinal chemistry letters [ACS Med Chem Lett] 2010 Dec 17; Vol. 2 (2), pp. 130-5. Date of Electronic Publication: 2010 Dec 17 (Print Publication: 2011). - Publication Year :
- 2010
-
Abstract
- Hepatitis C virus afflicts approximately 180 million people worldwide, and the development of direct acting antivirals may offer substantial benefit compared to the current standard of care. Accordingly, prodrugs of 2'-deoxy-2'-fluoro-2'-C-methylguanosine monophosphate analogues were prepared and evaluated for their anti-HCV efficacy and tolerability. These prodrugs demonstrated >1000 fold greater potency than the parent nucleoside in a cell-based replicon assay as a result of higher intracellular triphosphate levels. Further optimization led to the discovery of the clinical candidate PSI-353661, which has demonstrated strong in vitro inhibition against HCV without cytotoxicity and equipotent activity against both the wild type and the known S282T nucleoside/tide resistant replicon. PSI-353661 is currently in preclinical development for the treatment of HCV.
Details
- Language :
- English
- ISSN :
- 1948-5875
- Volume :
- 2
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- ACS medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 24900291
- Full Text :
- https://doi.org/10.1021/ml100209f