title: N-(2-Amino-phenyl)-4-(heteroarylmethyl)-benzamides as new histone deacetylase inhibitors.
abstract: A variety of N-(2-amino-phenyl)-4-(heteroarylmethyl)-benzamides were designed and synthesized. These compounds were shown to inhibit recombinant human HDAC1 with IC(50) values in the sub-micromolar range. In human cancer cells growing in culture these compounds induced hyperacetylation of histones, induced the expression of the tumor suppressor protein p21(WAF1/Cip1), and inhibited cellular proliferation. Certain compounds of this class also showed in vivo activity in various human tumor xenograft models in mice.
authors.affiliation: MethylGene Inc., Department of Chemistry, 7220 Frederick-Banting, Montréal, Que., Canada.
authors.forename: Arkadii
authors.initials: A
authors.lastname: Vaisburg
authors.forename: Isabelle
authors.initials: I
authors.lastname: Paquin
authors.forename: Naomy
authors.initials: N
authors.lastname: Bernstein
authors.forename: Sylvie
authors.initials: S
authors.lastname: Frechette
authors.forename: Frederic
authors.initials: F
authors.lastname: Gaudette
authors.forename: Silvana
authors.initials: S
authors.lastname: Leit
authors.forename: Oscar
authors.initials: O
authors.lastname: Moradei
authors.forename: Stephane
authors.initials: S
authors.lastname: Raeppel
authors.forename: Nancy
authors.initials: N
authors.lastname: Zhou
authors.forename: Giliane
authors.initials: G
authors.lastname: Bouchain
authors.forename: Soon Hyung
authors.initials: SH
authors.lastname: Woo
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Jin
authors.forename: Jeff
authors.initials: J
authors.lastname: Gillespie
authors.forename: James
authors.initials: J
authors.lastname: Wang
authors.forename: Marielle
authors.initials: M
authors.lastname: Fournel
authors.forename: Pu Theresa
authors.initials: PT
authors.lastname: Yan
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Trachy-Bourget
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Robert
authors.forename: Aihua
authors.initials: A
authors.lastname: Lu
authors.forename: Jimmy
authors.initials: J
authors.lastname: Yuk
authors.forename: Jubrail
authors.initials: J
authors.lastname: Rahil
authors.forename: A Robert
authors.initials: AR
authors.lastname: Macleod
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Besterman
authors.forename: Zuomei
authors.initials: Z
authors.lastname: Li
authors.forename: Daniel
authors.initials: D
authors.lastname: Delorme
mesh_terms: D000586:Amination; D000818:Animals; D001549:Benzamides / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008745:Methylation; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009525:Niacin / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry; D014664:Vasodilation / Q000187:drug effects; D062367:ortho-Aminobenzoates / Q000737:chemistry
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D009525:Niacin; D014508:Urea; D006655:Histone Deacetylases