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Discovery of novel cyanamide-based inhibitors of cathepsin C
Dramane Lainé1, Michael Palovich1, Brent McCleland1
1GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
Abstract:
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.
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