N-(2-Amino-phenyl)-4-(heteroarylmethyl)-benzamides as new histone deacetylase inhibitors.
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.
Vaisburg
Arkadii
A
MethylGene Inc., Department of Chemistry, 7220 Frederick-Banting, Montréal, Que., Canada.
Paquin
Isabelle
I
Bernstein
Naomy
N
Frechette
Sylvie
S
Gaudette
Frederic
F
Leit
Silvana
S
Moradei
Oscar
O
Raeppel
Stephane
S
Zhou
Nancy
N
Bouchain
Giliane
G
Woo
Soon Hyung
SH
Jin
Zhiyun
Z
Gillespie
Jeff
J
Wang
James
J
Fournel
Marielle
M
Yan
Pu Theresa
PT
Trachy-Bourget
Marie-Claude
MC
Robert
Marie-France
MF
Lu
Aihua
A
Yuk
Jimmy
J
Rahil
Jubrail
J
Macleod
A Robert
AR
Besterman
Jeffrey M
JM
Li
Zuomei
Z
Delorme
Daniel
D
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
D001549:Benzamides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D009525:Niacin; D014508:Urea; D006655:Histone Deacetylases