Conformation-based restrictions and scaffold replacements in the design of hepatitis C virus polymerase inhibitors: discovery of deleobuvir (BI 207127)
…, B Thavonekham, PL Beaulieu, G Kukolj…
文献索引：Beaulieu, Pierre L.; Bousquet, Yves; Gauthier, Jean; Gillard, James; Marquis, Martin; McKercher, Ginette; Pellerin, Charles; Valois, Serge; Kukolj, George Journal of Medicinal Chemistry, 2004 , vol. 47, # 27 p. 6884 - 6892
Conformational restrictions of flexible torsion angles were used to guide the identification of new chemotypes of HCV NS5B inhibitors. Sites for rigidification were based on an acquired conformational understanding of compound binding requirements and the roles of substituents in the free and bound states. Chemical bioisosteres of amide bonds were explored to improve cell-based potency. Examples are shown, including the design ...
