Synthesis and biological evaluation of new potent and selective HCV NS5A inhibitors
NS5A inhibitors are a new class of direct-acting antiviral agents which display very potent anti-HCV activity in vitro and in humans. Rationally designed modifications to the central biphenyl linkage of a known NS5A series led to selection of several compounds that were synthesized and evaluated in...
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Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2012-05, Vol.22 (10), p.3488-3491 |
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Hauptverfasser: | , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | NS5A inhibitors are a new class of direct-acting antiviral agents which display very potent anti-HCV activity in vitro and in humans. Rationally designed modifications to the central biphenyl linkage of a known NS5A series led to selection of several compounds that were synthesized and evaluated in a HCV genotype 1b replicon. The straight triphenyl linked compound 11a showed similar anti-HCV activity to the clinical compound BMS-790052 and a superior cytotoxicity profile in three different cell lines, with an EC50 value of 26pM and a therapeutic index of over four million in an HCV replicon assay. This triphenyl analog warrants further preclinical evaluation as an anti-HCV agent. |
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ISSN: | 0960-894X 1464-3405 |
DOI: | 10.1016/j.bmcl.2012.03.089 |