title: Arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 2: Optimization of P1 and N-aryl.
abstract: A systematic study of anilines led to the discovery of a metabolically robust fluoroindoline replacement for the alkoxy aniline toxicophore in 1. Investigations of the P1 pocket resulted in the discovery of a wide tolerance of functionality leading to the discovery of 11 as a potent and selective inhibitor of cathepsin S.
authors.affiliation: Genomics Institute of the Novartis Research Foundation, 10675 John J. Hopkins Dr., San Diego, CA 92121, USA. palper@gnf.org
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Alper
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Arnab K
authors.initials: AK
authors.lastname: Chatterjee
authors.forename: KhanhLinh T
authors.initials: KT
authors.lastname: Nguyen
authors.forename: David C
authors.initials: DC
authors.lastname: Tully
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: Tove
authors.initials: T
authors.lastname: Tuntland
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chang
authors.forename: Perry
authors.initials: P
authors.lastname: Gordon
authors.forename: Thomas
authors.initials: T
authors.lastname: Hollenbeck
authors.forename: Donald S
authors.initials: DS
authors.lastname: Karanewsky
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000586:Amination; D001555:Benzene Derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; 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; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D000431:Ethanol / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D001555:Benzene Derivatives; D015853:Cysteine Proteinase Inhibitors; D000431:Ethanol; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C028217:cathepsin S; D056657:Cathepsin K