Novel pyrrole- and 1,2,3-triazole-based 2,3-oxidosqualene cyclase inhibitors

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.

Graphical abstractPyrrole- 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. A preliminary structure–activity-relationship study of 3 was also conducted.Figure optionsDownload full-size imageDownload as PowerPoint slide