title: Design and synthesis of 3,3-piperidine hydroxamate analogs as selective TACE inhibitors.
abstract: Structure-based methods were used to design beta-sulfone 3,3-piperidine hydroxamates as TACE inhibitors with the aim of improving selectivity for TACE versus MMP-13. Several compounds in this series were synthesized and evaluated in enzymatic and cell-based assays. These analogs exhibit excellent in vitro potency against isolated TACE enzyme and show good selectivity for TACE over the related metalloproteases MMP-2, -13, and -14.
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA. hglombart@wyeth.com
authors.forename: Henry-Georges
authors.initials: HG
authors.lastname: Lombart
authors.forename: Eric
authors.initials: E
authors.lastname: Feyfant
authors.forename: Diane
authors.initials: D
authors.lastname: Joseph-McCarthy
authors.forename: Adrian
authors.initials: A
authors.lastname: Huang
authors.forename: Frank
authors.initials: F
authors.lastname: Lovering
authors.forename: LinHong
authors.initials: L
authors.lastname: Sun
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Congmei
authors.initials: C
authors.lastname: Zeng
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jeremy
authors.initials: J
authors.lastname: Levin
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors*; D000072198:ADAM17 Protein; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D051722:ADAM Proteins; D000072198:ADAM17 Protein