title: Anthranilate sulfonamide hydroxamate TACE inhibitors. Part 2: SAR of the acetylenic P1' group.
abstract: The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors bearing novel acetylenic P1' groups was explored. In particular, compound 4t bearing a butynyloxy P1' moiety has excellent in vitro potency against isolated TACE enzyme and in cells, good selectivity over MMP-1 and oral activity in an in vivo model of TNF-alpha production.
authors.affiliation: Wyeth-Ayerst Research, 401N. Middletown Road, Pearl River, NY 10965, USA. levinj@war.wyeth.com
authors.forename: J I
authors.initials: JI
authors.lastname: Levin
authors.forename: J M
authors.initials: JM
authors.lastname: Chen
authors.forename: M T
authors.initials: MT
authors.lastname: Du
authors.forename: F C
authors.initials: FC
authors.lastname: Nelson
authors.forename: L M
authors.initials: LM
authors.lastname: Killar
authors.forename: S
authors.initials: S
authors.lastname: Skala
authors.forename: A
authors.initials: A
authors.lastname: Sung
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: C J
authors.initials: CJ
authors.lastname: March
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*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*; 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