title: Synthesis and activity of quinolinylmethyl P1' alpha-sulfone piperidine hydroxamate inhibitors of TACE.
abstract: A series of alpha-sulfone piperidine hydroxamate TACE inhibitors 11a-n bearing a quinolinyl methyl P1' group was prepared, and their activity was compared to analogous alpha- and beta-sulfone piperidine hydroxamates with a butynyloxy P1' group. The quinolinyl methyl P1' group affords increased inhibitory enzyme activity relative to the corresponding butynyloxy P1' analogs in the alpha-sulfone piperidine hydroxamate series, and greater selectivity than the corresponding butynyloxy P1' analogs in the beta-sulfone piperidine hydroxamate series.
authors.affiliation: Chemical and Screening Science, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, USA. zhangc9@wyeth.com
authors.forename: Chunchun
authors.initials: C
authors.lastname: Zhang
authors.forename: Frank
authors.initials: F
authors.lastname: Lovering
authors.forename: Mark
authors.initials: M
authors.lastname: Behnke
authors.forename: Arie
authors.initials: A
authors.lastname: Zask
authors.forename: Vincent
authors.initials: V
authors.lastname: Sandanayaka
authors.forename: Linhong
authors.initials: L
authors.lastname: Sun
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Weixin
authors.initials: W
authors.lastname: Xu
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* / Q000378:metabolism; D000072198:ADAM17 Protein; D000818:Animals; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D006877:Hydroxamic Acids; D010880:Piperidines; D011480:Protease Inhibitors; D013450:Sulfones; C032727:piperidine; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse