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Discovery of novel cyanamide-based inhibitors of cathepsin C.

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.

SUBMITTER: Laine D

PROVIDER: S-EPMC4018094 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Discovery of novel cyanamide-based inhibitors of cathepsin C.

Lainé Dramane D Palovich Michael M McCleland Brent B Petitjean Emilie E Delhom Isabelle I Xie Haibo H Deng Jianghe J Lin Guoliang G Davis Roderick R Jolit Anais A Nevins Neysa N Zhao Baoguang B Villa Jim J Schneck Jessica J McDevitt Patrick P Midgett Robert R Kmett Casey C Umbrecht Sandra S Peck Brian B Davis Alicia Bacon AB Bettoun David D

ACS medicinal chemistry letters 20101110 2

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. ...[more]

PMID: 24900293

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