Arylamine based cathepsin K inhibitors: Investigating P3 heterocyclic substituents

A modification of novel cathepsin K inhibitors I was carried out. The structural design was aimed at reducing the lipophilic character of compounds I for obtaining better pharmacokinetic profiles. This modification afforded several less lipophilic compounds with good inhibitory activities and pharmacokinetic profiles, although the enzyme selectivity over cathepsin S was left at issue.

The synthesis, SARs, selectivity over other human cathepsins, and pharmacokinetics of heterocyclic substituted cathepsin K inhibitors are reported.Figure optionsDownload as PowerPoint slide