title: 4-(Heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides and their analogs as a novel class of histone deacetylase inhibitors.
abstract: The synthesis and biological evaluation of a variety of 4-(heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides and their analogs is described. Some of these compounds were shown to inhibit HDAC1 with IC(50) values below the micromolar range, induce hyperacetylation of histones, upregulate expression of the tumor suppressor p21(WAF1/Cip1), and inhibit proliferation of human cancer cells. In addition, certain compounds of this class were active in several human tumor xenograft models in vivo.
authors.affiliation: MethylGene Inc., Department of Medicinal Chemistry, 7220 Frederick-Banting, Montréal, QC, Canada.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fréchette
authors.forename: Silvana
authors.initials: S
authors.lastname: Leit
authors.forename: Soon Hyung
authors.initials: SH
authors.lastname: Woo
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lapointe
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jeannotte
authors.forename: Oscar
authors.initials: O
authors.lastname: Moradei
authors.forename: Isabelle
authors.initials: I
authors.lastname: Paquin
authors.forename: Giliane
authors.initials: G
authors.lastname: Bouchain
authors.forename: Stéphane
authors.initials: S
authors.lastname: Raeppel
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gaudette
authors.forename: Nancy
authors.initials: N
authors.lastname: Zhou
authors.forename: Arkadii
authors.initials: A
authors.lastname: Vaisburg
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: Ann
authors.initials: A
authors.lastname: Kalita
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Robert
authors.forename: Aihua
authors.initials: A
authors.lastname: Lu
authors.forename: Jubrail
authors.initials: J
authors.lastname: Rahil
authors.forename: A
authors.initials: A
authors.lastname: Robert 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: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001940:Breast / Q000166:cytology / Q000187:drug effects; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D045325:HCT116 Cells; D056284:Histone Deacetylase 1; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D001549:Benzamides; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D007093:Imidazoles; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1