Arylaminoethyl carbamates as a novel series of potent and selective cathepsin S inhibitors

We report a novel series of noncovalent inhibitors of cathepsin S. The synthesis of the peptidomimetic scaffold is described and structure–activity relationships of P3, P1, and P1′ subunits are discussed. Lead optimization to a non-peptidic scaffold has resulted in a new class of potent, highly selective, and orally bioavailable cathepsin S inhibitors.

Graphical abstractThe synthesis and SAR of a novel series of arylaminoethyl carbamates is reported as potent, highly selective, and orally bioavailable noncovalent inhibitors of cathepsin S.Figure optionsDownload full-size imageDownload as PowerPoint slide