4-(Heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides and their analogs as a novel class of histone deacetylase inhibitors.
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.
Fréchette
Sylvie
S
MethylGene Inc., Department of Medicinal Chemistry, 7220 Frederick-Banting, Montréal, QC, Canada.
Leit
Silvana
S
Woo
Soon Hyung
SH
Lapointe
Guillaume
G
Jeannotte
Guillaume
G
Moradei
Oscar
O
Paquin
Isabelle
I
Bouchain
Giliane
G
Raeppel
Stéphane
S
Gaudette
Frédéric
F
Zhou
Nancy
N
Vaisburg
Arkadii
A
Fournel
Marielle
M
Yan
Pu Theresa
PT
Trachy-Bourget
Marie-Claude
MC
Kalita
Ann
A
Robert
Marie-France
MF
Lu
Aihua
A
Rahil
Jubrail
J
Robert Macleod
A
A
Besterman
Jeffrey M
JM
Li
Zuomei
Z
Delorme
Daniel
D
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
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