title: N-hydroxyformamide peptidomimetics as TACE/matrix metalloprotease inhibitors: oral activity via P1' isobutyl substitution.
abstract: N-Hydroxyformamide-class metalloprotease inhibitors were designed and synthesized, which have potent broad-spectrum activity versus matrix metalloproteases and TNF-alpha converting enzyme (TACE). Compound 13c possesses good oral and intravenous pharmacokinetics in the rat and dog.
authors.affiliation: GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709, USA. dm12907@glaxowellcome.com
authors.forename: D L
authors.initials: DL
authors.lastname: Musso
authors.forename: M W
authors.initials: MW
authors.lastname: Andersen
authors.forename: R C
authors.initials: RC
authors.lastname: Andrews
authors.forename: R
authors.initials: R
authors.lastname: Austin
authors.forename: E J
authors.initials: EJ
authors.lastname: Beaudet
authors.forename: J D
authors.initials: JD
authors.lastname: Becherer
authors.forename: D G
authors.initials: DG
authors.lastname: Bubacz
authors.forename: D M
authors.initials: DM
authors.lastname: Bickett
authors.forename: J H
authors.initials: JH
authors.lastname: Chan
authors.forename: J G
authors.initials: JG
authors.lastname: Conway
authors.forename: D J
authors.initials: DJ
authors.lastname: Cowan
authors.forename: M D
authors.initials: MD
authors.lastname: Gaul
authors.forename: K C
authors.initials: KC
authors.lastname: Glennon
authors.forename: K M
authors.initials: KM
authors.lastname: Hedeen
authors.forename: M H
authors.initials: MH
authors.lastname: Lambert
authors.forename: M A
authors.initials: MA
authors.lastname: Leesnitzer
authors.forename: D L
authors.initials: DL
authors.lastname: McDougald
authors.forename: J L
authors.initials: JL
authors.lastname: Mitchell
authors.forename: M L
authors.initials: ML
authors.lastname: Moss
authors.forename: M H
authors.initials: MH
authors.lastname: Rabinowitz
authors.forename: M C
authors.initials: MC
authors.lastname: Rizzolio
authors.forename: L T
authors.initials: LT
authors.lastname: Schaller
authors.forename: J B
authors.initials: JB
authors.lastname: Stanford
authors.forename: T
authors.initials: T
authors.lastname: Tippin
authors.forename: J R
authors.initials: JR
authors.lastname: Warner
authors.forename: L G
authors.initials: LG
authors.lastname: Whitesell
authors.forename: R W
authors.initials: RW
authors.lastname: Wiethe
mesh_terms: D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000818:Animals; D004285:Dogs; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D005559:Formamides / Q000737:chemistry / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D005559:Formamides; D061965:Matrix Metalloproteinase Inhibitors; D009842:Oligopeptides; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606464:Adam17 protein, rat