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Merck

Discovery of novel cyanamide-based inhibitors of cathepsin C.

ACS medicinal chemistry letters (2011-02-10)
Dramane Lainé, Michael Palovich, Brent McCleland, Emilie Petitjean, Isabelle Delhom, Haibo Xie, Jianghe Deng, Guoliang Lin, Roderick Davis, Anais Jolit, Neysa Nevins, Baoguang Zhao, Jim Villa, Jessica Schneck, Patrick McDevitt, Robert Midgett, Casey Kmett, Sandra Umbrecht, Brian Peck, Alicia Bacon Davis, David Bettoun
ZUSAMMENFASSUNG

The discovery of potent and selective cyanamide-based inhibitors of the cysteine protease cathepsin C is detailed. Optimization of the template with regard to plasma stability led to the identification of compound 17, a potent cathepsin C inhibitor with excellent selectivity over other cathepsins and potent in vivo activity in a cigarette smoke mouse model.