title: Diphenylmethylene hydroxamic acids as selective class IIa histone deacetylase inhibitors.
abstract: We have identified a series of diphenylmethylene hydroxamic acids as novel and selective HDAC class IIa inhibitors. The original hit, N-hydroxy-2,2-diphenylacetamide (6), has sub-micromolar class IIa HDAC inhibitory activity, while the rigidified oxygen analogue, N-hydroxy-9H-xanthene-9-carboxamide (13), is slightly more selective for HDAC7 with an IC(50) of 0.05muM. Substitution of 6 allows for the modulation of selectivity and potency amongst the class IIa HDAC isotypes.
authors.affiliation: MethylGene Inc., Department of Medicinal Chemistry, 7220 Frederick-Banting, Montréal, Québec, Canada H4S 2A1.
authors.forename: Pierre
authors.initials: P
authors.lastname: Tessier
authors.forename: David V
authors.initials: DV
authors.lastname: Smil
authors.forename: Amal
authors.initials: A
authors.lastname: Wahhab
authors.forename: Silvana
authors.initials: S
authors.lastname: Leit
authors.forename: Jubrail
authors.initials: J
authors.lastname: Rahil
authors.forename: Zuomei
authors.initials: Z
authors.lastname: Li
authors.forename: Robert
authors.initials: R
authors.lastname: Déziel
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Besterman
mesh_terms: D002460:Cell Line; D004158:Diphenylacetic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D014966:Xanthenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004158:Diphenylacetic Acids; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C545109:N-hydroxy-2,2-diphenylacetamide; C545110:N-hydroxy-9H-xanthene-9-carboxamide; D020033:Protein Isoforms; D014966:Xanthenes; D006655:Histone Deacetylases