Hendricks Robert T, Fell Jay B, Blake James F, Fischer John P, Robinson John E, Spencer Stacey R, Stengel Peter J, Bernacki April L, Leveque Vincent J P, Le Pogam Sophie, Rajyaguru Sonal, Najera Isabel, Josey John A, Harris Jason R, Swallow Steven
Roche Palo Alto, LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA.
Bioorg Med Chem Lett. 2009 Jul 1;19(13):3637-41. doi: 10.1016/j.bmcl.2009.04.119. Epub 2009 May 3.
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.
已对一系列苯并噻二嗪和1,4 - 苯并噻嗪NS5b抑制剂中分子内氢键的重要性进行了探究。已运用计算分析来比较每个系列的质子化形式与阴离子形式，并且我们证明，使用阴离子形式能最好地解释对丙型肝炎病毒NS5b聚合酶的活性。还讨论了多种新类似物的合成及其构效关系。
