title: Synthesis and SAR of diazepine and thiazepine TACE and MMP inhibitors.
abstract: Potent and selective TACE and MMP inhibitors utilizing the diazepine and thiazepine ring systems were synthesized and evaluated for biological activity in in vitro and in vivo models of TNF-alpha release. Oral activity in the mouse LPS model of TNF-alpha release was seen. Efficacy in the mouse collagen induced arthritis model was achieved with diazepine 20.
authors.affiliation: Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, USA. zaska@wyeth.com
authors.forename: Arie
authors.initials: A
authors.lastname: Zask
authors.forename: Joshua
authors.initials: J
authors.lastname: Kaplan
authors.forename: XueMei
authors.initials: X
authors.lastname: Du
authors.forename: Gloria
authors.initials: G
authors.lastname: MacEwan
authors.forename: Vincent
authors.initials: V
authors.lastname: Sandanayaka
authors.forename: Nancy
authors.initials: N
authors.lastname: Eudy
authors.forename: Jeremy
authors.initials: J
authors.lastname: Levin
authors.forename: Guixian
authors.initials: G
authors.lastname: Jin
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Terri
authors.initials: T
authors.lastname: Cummons
authors.forename: Dauphine
authors.initials: D
authors.lastname: Barone
authors.forename: Semiramis
authors.initials: S
authors.lastname: Ayral-Kaloustian
authors.forename: Jerauld
authors.initials: J
authors.lastname: Skotnicki
mesh_terms: D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000818:Animals; D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051379:Mice; D008807:Mice, Inbred BALB C; D008956:Models, Chemical; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D001381:Azepines; D061965:Matrix Metalloproteinase Inhibitors; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606463:Adam17 protein, mouse