title: Synthesis and structure-activity relationship of a novel, non-hydroxamate series of TNF-alpha converting enzyme inhibitors.
abstract: A novel series of TNF-alpha converting enzyme (TACE) inhibitors which are non-hydroxamate have been discovered. These compounds use a triazolethione moiety as the zinc binding ligand and exhibit IC50 values from 1.5 to 100 nM in a porcine TACE assay. They also have excellent selectivities over other MMPs.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA. john.gilmore@bms.com
authors.forename: John L
authors.initials: JL
authors.lastname: Gilmore
authors.forename: Bryan W
authors.initials: BW
authors.lastname: King
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Asakawa
authors.forename: Kimberly
authors.initials: K
authors.lastname: Harrison
authors.forename: Andrew
authors.initials: A
authors.lastname: Tebben
authors.forename: James E
authors.initials: JE
authors.lastname: Sheppeck
authors.forename: Rui-Qin
authors.initials: RQ
authors.lastname: Liu
authors.forename: Maryanne
authors.initials: M
authors.lastname: Covington
authors.forename: James J-W
authors.initials: JJ
authors.lastname: Duan
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors*; D000072198:ADAM17 Protein; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D051722:ADAM Proteins; D000072198:ADAM17 Protein