Institute of Microbial Chemistry, Tokyo, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
Bioorg Med Chem Lett. 2010 Oct 1;20(19):5807-10. doi: 10.1016/j.bmcl.2010.07.131. Epub 2010 Aug 3.
Pyrrole- and 1,2,3-triazole-based 2,3-oxidosqualene cyclase (OSC) inhibitors 3 and 4 were discovered by conducting a virtual screening, a docking study based on the crystallographic structure of OSC, and biological assays. The hit rate of the assays was increased by establishing appropriate substructural filters in the virtual screening stage. Amide derivatives of 8 and 12 preserved the inhibitory activity of parent compound 3, which provided a reasonable starting point for further structure-activity-relationship (SAR) studies on related compounds.
吡咯并[1,2-a]1,2,4-三唑基 2,3-氧化鲨烯环化酶 (OSC) 抑制剂 3 和 4 是通过虚拟筛选、基于 OSC 晶体结构的对接研究和生物测定发现的。通过在虚拟筛选阶段建立适当的亚结构筛选，可以提高测定的命中率。8 和 12 的酰胺衍生物保留了母体化合物 3 的抑制活性，这为进一步研究相关化合物的构效关系 (SAR) 提供了合理的起点。
