N-Arylaminonitriles as bioavailable peptidomimetic inhibitors of cathepsin B

To improve the pharmacokinetics of a previously reported series of dipeptidyl nitrile cathepsin B inhibitors, the P 2–P 3 amide group was replaced with an arylamine. Further optimization of this template resulted in highly potent and selective inhibitors with excellent oral availability. To improve the pharmacokinetics of a previously reported series of dipeptidyl nitrile cathepsin B inhibitors, the P 2–P 3 amide group was replaced with an arylamine. Further optimization of this template resulted in highly potent and selective inhibitors with excellent oral availability.