Discovery of fluorobenzimidazole HCV NS5A inhibitors.

Autor: Randolph JT; AbbVie Inc., North Chicago, IL, USA., Flentge CA; AbbVie Inc., North Chicago, IL, USA., Donner P; AbbVie Inc., North Chicago, IL, USA., Rockway TW; AbbVie Inc., North Chicago, IL, USA., Patel SV; AbbVie Inc., North Chicago, IL, USA., Nelson L; AbbVie Inc., North Chicago, IL, USA., Hutchinson DK; AbbVie Inc., North Chicago, IL, USA., Mondal R; AbbVie Inc., North Chicago, IL, USA., Mistry N; AbbVie Inc., North Chicago, IL, USA., Reisch T; AbbVie Inc., North Chicago, IL, USA., Dekhtyar T; AbbVie Inc., North Chicago, IL, USA., Krishnan P; AbbVie Inc., North Chicago, IL, USA., Pilot-Matias T; AbbVie Inc., North Chicago, IL, USA., Stolarik DF; AbbVie Inc., North Chicago, IL, USA., Beno DWA; AbbVie Inc., North Chicago, IL, USA., Wagner R; AbbVie Inc., North Chicago, IL, USA., Maring C; AbbVie Inc., North Chicago, IL, USA., Kati WM; AbbVie Inc., North Chicago, IL, USA.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2016 Nov 15; Vol. 26 (22), pp. 5462-5467. Date of Electronic Publication: 2016 Oct 13.
DOI: 10.1016/j.bmcl.2016.10.030
Abstrakt: Research toward a next-generation HCV NS5A inhibitor has identified fluorobenzimidazole analogs that demonstrate potent, broad-genotype in vitro activity against HCV genotypes 1-6 replicons as well as HCV NS5A variants that are orders of magnitude less susceptible to inhibition by first-generation NS5A inhibitors in comparison to wild-type replicons. The fluorobenzimidazole inhibitors have improved pharmacokinetic properties in comparison to non-fluorinated benzimidazole analogs. Discovery of these inhibitors was facilitated by exploring SAR in a structurally simplified inhibitor series.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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