| Structural highlights
Publication Abstract from PubMed
Benzothiazine-substituted tetramic acids were discovered as highly potent non-nucleoside inhibitors of HCV NS5B polymerase. X-ray crystallography studies confirmed the binding mode of these inhibitors with HCV NS5B polymerase. Rational optimization of time dependent inactivation of CYP 3A4 and clearance was accomplished by incorporation of electron-withdrawing groups to the benzothiazine core.
Non-nucleoside inhibitors of HCV polymerase NS5B. Part 3: synthesis and optimization studies of benzothiazine-substituted tetramic acids.,de Vicente J, Hendricks RT, Smith DB, Fell JB, Fischer J, Spencer SR, Stengel PJ, Mohr P, Robinson JE, Blake JF, Hilgenkamp RK, Yee C, Zhao J, Elworthy TR, Tracy J, Chin E, Li J, Lui A, Wang B, Oshiro C, Harris SF, Ghate M, Leveque VJ, Najera I, Le Pogam S, Rajyaguru S, Ao-Ieong G, Alexandrova L, Fitch B, Brandl M, Masjedizadeh M, Wu SY, de Keczer S, Voronin T Bioorg Med Chem Lett. 2009 Oct 1;19(19):5648-51. Epub 2009 Aug 8. PMID:19700319[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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References
- ↑ de Vicente J, Hendricks RT, Smith DB, Fell JB, Fischer J, Spencer SR, Stengel PJ, Mohr P, Robinson JE, Blake JF, Hilgenkamp RK, Yee C, Zhao J, Elworthy TR, Tracy J, Chin E, Li J, Lui A, Wang B, Oshiro C, Harris SF, Ghate M, Leveque VJ, Najera I, Le Pogam S, Rajyaguru S, Ao-Ieong G, Alexandrova L, Fitch B, Brandl M, Masjedizadeh M, Wu SY, de Keczer S, Voronin T. Non-nucleoside inhibitors of HCV polymerase NS5B. Part 3: synthesis and optimization studies of benzothiazine-substituted tetramic acids. Bioorg Med Chem Lett. 2009 Oct 1;19(19):5648-51. Epub 2009 Aug 8. PMID:19700319 doi:10.1016/j.bmcl.2009.08.023
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