Non-nucleoside inhibitors of HCV NS5B polymerase. Part 1: Synthetic and computational exploration of the binding modes of benzothiadiazine and 1,4-benzothiazine HCV NS5b polymerase inhibitors.

Autor: Hendricks RT; Roche Palo Alto, LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. Than.Hendricks@Roche.com, Fell JB, Blake JF, Fischer JP, Robinson JE, Spencer SR, Stengel PJ, Bernacki AL, Leveque VJ, Le Pogam S, Rajyaguru S, Najera I, Josey JA, Harris JR, Swallow S
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2009 Jul 01; Vol. 19 (13), pp. 3637-41. Date of Electronic Publication: 2009 May 03.
DOI: 10.1016/j.bmcl.2009.04.119
Abstrakt: The importance of internal hydrogen bonding in a series of benzothiadiazine and 1,4-benzothiazine NS5b inhibitors has been explored. Computational analysis has been used to compare the protonated vs. anionic forms of each series and we demonstrate that activity against HCV NS5b polymerase is best explained using the anionic forms. The syntheses and structure-activity relationships for a variety of new analogs are also discussed.
Databáze: MEDLINE
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