title: Acetylenic TACE inhibitors. Part 1. SAR of the acyclic sulfonamide hydroxamates.
abstract: The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors, all bearing a butynyloxy P1' group, was explored. In particular, compound 5j has excellent in vitro potency against isolated TACE enzyme and in cells, good selectivity over MMP-1 and MMP-9, and oral activity in an in vivo model of TNF-alpha production and a collagen-induced arthritis model.
authors.affiliation: Wyeth Research, 401 N Middletown Rd, Pearl River, NY 10965, USA. levinji@wyeth.com
authors.forename: J I
authors.initials: JI
authors.lastname: Levin
authors.forename: J M
authors.initials: JM
authors.lastname: Chen
authors.forename: K
authors.initials: K
authors.lastname: Cheung
authors.forename: D
authors.initials: D
authors.lastname: Cole
authors.forename: C
authors.initials: C
authors.lastname: Crago
authors.forename: E Delos
authors.initials: ED
authors.lastname: Santos
authors.forename: X
authors.initials: X
authors.lastname: Du
authors.forename: G
authors.initials: G
authors.lastname: Khafizova
authors.forename: G
authors.initials: G
authors.lastname: MacEwan
authors.forename: C
authors.initials: C
authors.lastname: Niu
authors.forename: E J
authors.initials: EJ
authors.lastname: Salaski
authors.forename: A
authors.initials: A
authors.lastname: Zask
authors.forename: T
authors.initials: T
authors.lastname: Cummons
authors.forename: A
authors.initials: A
authors.lastname: Sung
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.forename: S
authors.initials: S
authors.lastname: Ayral-Kaloustian
authors.forename: G
authors.initials: G
authors.lastname: Jin
authors.forename: R
authors.initials: R
authors.lastname: Cowling
authors.forename: D
authors.initials: D
authors.lastname: Barone
authors.forename: K M
authors.initials: KM
authors.lastname: Mohler
authors.forename: R A
authors.initials: RA
authors.lastname: Black
authors.forename: J S
authors.initials: JS
authors.lastname: Skotnicki
mesh_terms: D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000114:Acetylene / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000737:chemistry; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry; D062367:ortho-Aminobenzoates / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D013449:Sulfonamides; D062367:ortho-Aminobenzoates; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; D000114:Acetylene