title: Discovery of novel hydantoins as selective non-hydroxamate inhibitors of tumor necrosis factor-alpha converting enzyme (TACE).
abstract: A series of novel hydantoins was designed and synthesized as structural alternatives to hydroxamate inhibitors of TACE. 5-Mono- and di-substituted hydantoins exhibited activity with IC50 values of 11-60 nM against porcine TACE in vitro and excellent selectivity against other MMPs.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Discovery Chemistry, PO Box 4000, Princeton, NJ 08543-4000, USA. jim.sheppeck@bms.com
authors.forename: James E
authors.initials: JE
authors.lastname: Sheppeck
authors.forename: John L
authors.initials: JL
authors.lastname: Gilmore
authors.forename: Anle
authors.initials: A
authors.lastname: Yang
authors.forename: Xiao-Tao
authors.initials: XT
authors.lastname: Chen
authors.forename: Chu-Biao
authors.initials: CB
authors.lastname: Xue
authors.forename: John
authors.initials: J
authors.lastname: Roderick
authors.forename: Rui-Qin
authors.initials: RQ
authors.lastname: Liu
authors.forename: Maryanne B
authors.initials: MB
authors.lastname: Covington
authors.forename: Carl P
authors.initials: CP
authors.lastname: Decicco
authors.forename: James J-W
authors.initials: JJ
authors.lastname: Duan
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors*; D000072198:ADAM17 Protein; D000818:Animals; D015195:Drug Design; D006827:Hydantoins / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013552:Swine
chemical_list: D006827:Hydantoins; D051722:ADAM Proteins; D000072198:ADAM17 Protein