title: Arylaminoethyl carbamates as a novel series of potent and selective cathepsin S inhibitors.
abstract: We report a novel series of noncovalent inhibitors of cathepsin S. The synthesis of the peptidomimetic scaffold is described and structure-activity relationships of P3, P1, and P1' subunits are discussed. Lead optimization to a non-peptidic scaffold has resulted in a new class of potent, highly selective, and orally bioavailable cathepsin S inhibitors.
authors.affiliation: Genomics Institute of the Novartis Research Foundation, 10675 John J. Hopkins Dr., San Diego, CA 92121, USA. dtully@gnf.org
authors.forename: David C
authors.initials: DC
authors.lastname: Tully
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Arnab K
authors.initials: AK
authors.lastname: Chatterjee
authors.forename: Phil B
authors.initials: PB
authors.lastname: Alper
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Williams
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Roberts
authors.forename: Daniel
authors.initials: D
authors.lastname: Mutnick
authors.forename: David H
authors.initials: DH
authors.lastname: Woodmansee
authors.forename: Thomas
authors.initials: T
authors.lastname: Hollenbeck
authors.forename: Perry
authors.initials: P
authors.lastname: Gordon
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chang
authors.forename: Tove
authors.initials: T
authors.lastname: Tuntland
authors.forename: Christine
authors.initials: C
authors.lastname: Tumanut
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Harris
authors.forename: Donald S
authors.initials: DS
authors.lastname: Karanewsky
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002219:Carbamates / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D002219:Carbamates; D009842:Oligopeptides; D011480:Protease Inhibitors; D002403:Cathepsins; C028217:cathepsin S