title: Design and synthesis of butynyloxyphenyl beta-sulfone piperidine hydroxamates as TACE inhibitors.
abstract: A series of butynyloxyphenyl beta-sulfone piperidine hydroxamate TACE inhibitors was designed and synthesized. The resulting structure-activity relationship and MMP selectivity of the series were examined. Of the compounds investigated, 17s has excellent in vitro potency against isolated TACE enzyme, shows good selectivity over MMP-1, -2, -7, -8, -9, -13, and -14, and oral activity in an in vivo mouse model of TNF-alpha production.
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, 401 N. Middletown Rd., Pearl River, NY 10965, USA. ParkK3@wyeth.com
authors.forename: Kaapjoo
authors.initials: K
authors.lastname: Park
authors.forename: Alexis
authors.initials: A
authors.lastname: Aplasca
authors.forename: Mila T
authors.initials: MT
authors.lastname: Du
authors.forename: LinHong
authors.initials: L
authors.lastname: Sun
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jeremy I
authors.initials: JI
authors.lastname: Levin
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors*; D000072198:ADAM17 Protein; D000818:Animals; D015195:Drug Design; D051379:Mice; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D010880:Piperidines; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606463:Adam17 protein, mouse