title: Synthesis and evaluation of arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 3: heterocyclic P3.
abstract: A series of N(alpha)-2-benzoxazolyl-alpha-amino acid-(arylaminoethyl)amides were identified as potent, selective, and noncovalent inhibitors of cathepsin S. Structure-activity relationships including strategies for modulating the selectivities among cathepsins S, K, and L, and in vivo pharmacokinetics are discussed. A X-ray structure of compound 3 bound to the active site of cathepsin S is also reported.
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: Phil B
authors.initials: PB
authors.lastname: Alper
authors.forename: Arnab K
authors.initials: AK
authors.lastname: Chatterjee
authors.forename: Robert
authors.initials: R
authors.lastname: Epple
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Roberts
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Williams
authors.forename: KhanhLinh T
authors.initials: KT
authors.lastname: Nguyen
authors.forename: David H
authors.initials: DH
authors.lastname: Woodmansee
authors.forename: Christine
authors.initials: C
authors.lastname: Tumanut
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Glen
authors.initials: G
authors.lastname: Spraggon
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chang
authors.forename: Tove
authors.initials: T
authors.lastname: Tuntland
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Harris
authors.forename: Donald S
authors.initials: DS
authors.lastname: Karanewsky
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D051381:Rats
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D002403:Cathepsins; C028217:cathepsin S