title: (2-amino-phenyl)-amides of omega-substituted alkanoic acids as new histone deacetylase inhibitors.
abstract: A variety of omega-substituted alkanoic acid (2-amino-phenyl)-amides were designed and synthesized. These compounds were shown to inhibit recombinant human histone deacetylases (HDACs) with IC(50) values in the low micromolar range and induce hyperacetylation of histones in whole cells. They induced expression of p21WAF1/Cip1 and caused cell-cycle arrest in human cancer cells. Compounds in this class showed efficacy in human tumor xenograft models.
authors.affiliation: Department of Medicinal Chemistry, MethylGene Inc., 7220 Frederick-Banting, Montreal, Quebec, Canada H4S 2A1. vaisburga@methylgene.com
authors.forename: Arkadii
authors.initials: A
authors.lastname: Vaisburg
authors.forename: Naomy
authors.initials: N
authors.lastname: Bernstein
authors.forename: Sylvie
authors.initials: S
authors.lastname: Frechette
authors.forename: Martin
authors.initials: M
authors.lastname: Allan
authors.forename: Elie
authors.initials: E
authors.lastname: Abou-Khalil
authors.forename: Silvana
authors.initials: S
authors.lastname: Leit
authors.forename: Oscar
authors.initials: O
authors.lastname: Moradei
authors.forename: Giliane
authors.initials: G
authors.lastname: Bouchain
authors.forename: James
authors.initials: J
authors.lastname: Wang
authors.forename: Soon Hyung
authors.initials: SH
authors.lastname: Woo
authors.forename: Marielle
authors.initials: M
authors.lastname: Fournel
authors.forename: Pu T
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: Carole
authors.initials: C
authors.lastname: Beaulieu
authors.forename: Zuomei
authors.initials: Z
authors.lastname: Li
authors.forename: A Robert
authors.initials: AR
authors.lastname: MacLeod
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Besterman
authors.forename: Daniel
authors.initials: D
authors.lastname: Delorme
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases