Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors?

Article abstract of DOI:10.1016/j.bmcl.2005.10.108

Starting from potent aldehyde inhibitors with poor drug properties, derivatization to semicarbazones led to the identification of a series of semicarbazone-based cathepsin K inhibitors with greater solubility and better pharmacokinetic profiles than their parent aldehydes. Furthermore, a representative semicarbazone inhibitor attenuated bone resorption in an ex vivo rat calvarial bone resorption model. However, based on enzyme inhibition comparisons at neutral pH, semicarbazone hydrolysis rates, and ¹³C NMR experiments, these semicarbazones probably function as prodrugs of aldehydes.