title: Design and synthesis of arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 1.
abstract: A series of Nalpha-acyl-alpha-amino acid-(arylaminoethyl)amides were found to be potent and noncovalent cathepsin S inhibitors. Compound 20 possessed high cathepsin S affinity (Ki=3.3 nM) and showed excellent selectivity over cathepsin K, L, F, and V. Molecular modeling, design, synthesis, and in vitro activity are described.
authors.affiliation: Genomics Institute of the Novartis Research Foundation, 10675 John J. Hopkins Dr., San Diego, CA 92121, USA. hliu@gnf.org
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: David C
authors.initials: DC
authors.lastname: Tully
authors.forename: Robert
authors.initials: R
authors.lastname: Epple
authors.forename: Badry
authors.initials: B
authors.lastname: Bursulaya
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Harris
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Williams
authors.forename: Ross
authors.initials: R
authors.lastname: Russo
authors.forename: Christine
authors.initials: C
authors.lastname: Tumanut
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Roberts
authors.forename: Phil B
authors.initials: PB
authors.lastname: Alper
authors.forename: Yun
authors.initials: Y
authors.lastname: He
authors.forename: Donald S
authors.initials: DS
authors.lastname: Karanewsky
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry*; D000586:Amination; D001665:Binding Sites; D056657:Cathepsin K; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D000431:Ethanol / Q000737:chemistry*; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D011480:Protease Inhibitors; D000431:Ethanol; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C028217:cathepsin S; D056657:Cathepsin K