title: 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.
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Dramane
authors.initials: D
authors.lastname: Lainé
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Palovich
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Brent
authors.initials: B
authors.lastname: McCleland
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Emilie
authors.initials: E
authors.lastname: Petitjean
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Delhom
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Haibo
authors.initials: H
authors.lastname: Xie
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Jianghe
authors.initials: J
authors.lastname: Deng
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Lin
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Roderick
authors.initials: R
authors.lastname: Davis
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Anais
authors.initials: A
authors.lastname: Jolit
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Neysa
authors.initials: N
authors.lastname: Nevins
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Baoguang
authors.initials: B
authors.lastname: Zhao
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Jim
authors.initials: J
authors.lastname: Villa
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Jessica
authors.initials: J
authors.lastname: Schneck
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Patrick
authors.initials: P
authors.lastname: McDevitt
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Midgett
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Casey
authors.initials: C
authors.lastname: Kmett
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Sandra
authors.initials: S
authors.lastname: Umbrecht
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Peck
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: Alicia Bacon
authors.initials: AB
authors.lastname: Davis
authors.affiliation: GlaxoSmithKline, Respiratory CEDD, 709 Swedeland Road, P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, United States.
authors.forename: David
authors.initials: D
authors.lastname: Bettoun
keywords: Cathepsin C inhibitors; cigarette smoke; cyanamides; potent; selective