title: Synthesis and SAR of bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors.
abstract: Potent and selective bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors were synthesized by a novel convergent route. Selectivity and efficacy versus MMPs and TACE could be controlled by appropriate substitution on the scaffolds and by variation of the P1' group. Select compounds were found to be effective in in vivo models of arthritis.
authors.affiliation: Wyeth-Ayerst Research, 401N. Middletown Road, Pearl River, NY 10965, USA. zaska@wyeth.com
authors.forename: A
authors.initials: A
authors.lastname: Zask
authors.forename: Y
authors.initials: Y
authors.lastname: Gu
authors.forename: J D
authors.initials: JD
authors.lastname: Albright
authors.forename: X
authors.initials: X
authors.lastname: Du
authors.forename: M
authors.initials: M
authors.lastname: Hogan
authors.forename: J I
authors.initials: JI
authors.lastname: Levin
authors.forename: J M
authors.initials: JM
authors.lastname: Chen
authors.forename: L M
authors.initials: LM
authors.lastname: Killar
authors.forename: A
authors.initials: A
authors.lastname: Sung
authors.forename: J F
authors.initials: JF
authors.lastname: DiJoseph
authors.forename: M A
authors.initials: MA
authors.lastname: Sharr
authors.forename: C E
authors.initials: CE
authors.lastname: Roth
authors.forename: S
authors.initials: S
authors.lastname: Skala
authors.forename: G
authors.initials: G
authors.lastname: Jin
authors.forename: R
authors.initials: R
authors.lastname: Cowling
authors.forename: K M
authors.initials: KM
authors.lastname: Mohler
authors.forename: D
authors.initials: D
authors.lastname: Barone
authors.forename: R
authors.initials: R
authors.lastname: Black
authors.forename: C
authors.initials: C
authors.lastname: March
authors.forename: J S
authors.initials: JS
authors.lastname: Skotnicki
mesh_terms: D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000818:Animals; D001168:Arthritis / Q000188:drug therapy / Q000473:pathology; D001682:Biological Availability; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002356:Cartilage / Q000187:drug effects / Q000473:pathology; D002417:Cattle; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051379:Mice; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606463:Adam17 protein, mouse; C000606464:Adam17 protein, rat