Design, synthesis, and screen of cathepsin K inhibitors

We synthesized a series of epoxysuccinic acid derivatives and evaluated their in vitro cathepsin K inhibitory activity The screening results show that the potency of compounds 9e, 9d, 9p, 9j and 9k (IC50 ≤ 0.005 μmol/L) were equal to or greater than that of the lead compound 9a. Less hydrophobic compounds showed weaker potency, which can be explained by the hydrophobic nature of the cathepsin K binding pockets.

Graphical abstractWe synthesized a series of epoxysuccinic acid derivatives and evaluated their in vitro cathepsin K inhibitory activity. The screeningresults show that the potency of compounds 9e, 9d, 9p, 9j and 9k (IC50 ≤ 0.005 μmol/L) were equal to or greater than that of the lead compound 9a.Figure optionsDownload full-size imageDownload as PowerPoint slide