title: Design and synthesis of 4-[(s-triazin-2-ylamino)methyl]-N-(2-aminophenyl)-benzamides and their analogues as a novel class of histone deacetylase inhibitors.
abstract: Inhibition of histone deacetylases (HDAC) is emerging as a new strategy in human cancer therapy. The synthesis and biological evaluation of a variety of 4-(heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides is presented herein. From the different series bearing a six-membered heteroaromatic ring studied, the s-triazine series showed the best HDAC1 enzyme and in vitro anti-proliferative activities with IC(50) values below micromolar range. Some of these compounds can also significantly reduce tumor growth in human tumor xenograft models in mice.
authors.affiliation: MethylGene Inc., Department of Medicinal Chemistry, 7220 Frederick-Banting, Montréal, QC, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Paquin
authors.forename: Stéphane
authors.initials: S
authors.lastname: Raeppel
authors.forename: Silvana
authors.initials: S
authors.lastname: Leit
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gaudette
authors.forename: Nancy
authors.initials: N
authors.lastname: Zhou
authors.forename: Oscar
authors.initials: O
authors.lastname: Moradei
authors.forename: Oscar
authors.initials: O
authors.lastname: Saavedra
authors.forename: Naomy
authors.initials: N
authors.lastname: Bernstein
authors.forename: Franck
authors.initials: F
authors.lastname: Raeppel
authors.forename: Giliane
authors.initials: G
authors.lastname: Bouchain
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fréchette
authors.forename: Soon H
authors.initials: SH
authors.lastname: Woo
authors.forename: Arkadii
authors.initials: A
authors.lastname: Vaisburg
authors.forename: Marielle
authors.initials: M
authors.lastname: Fournel
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: Marie-Claude
authors.initials: MC
authors.lastname: Trachy-Bourget
authors.forename: Pu Theresa
authors.initials: PT
authors.lastname: Yan
authors.forename: Jianhong
authors.initials: J
authors.lastname: Liu
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: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D011743:Pyrimidines / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D011743:Pyrimidines; D014227:Triazines; C523184:mocetinostat