(2-amino-phenyl)-amides of omega-substituted alkanoic acids as new histone deacetylase inhibitors.
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.
Vaisburg
Arkadii
A
Department of Medicinal Chemistry, MethylGene Inc., 7220 Frederick-Banting, Montreal, Quebec, Canada H4S 2A1. vaisburga@methylgene.com
Bernstein
Naomy
N
Frechette
Sylvie
S
Allan
Martin
M
Abou-Khalil
Elie
E
Leit
Silvana
S
Moradei
Oscar
O
Bouchain
Giliane
G
Wang
James
J
Woo
Soon Hyung
SH
Fournel
Marielle
M
Yan
Pu T
PT
Trachy-Bourget
Marie-Claude
MC
Kalita
Ann
A
Beaulieu
Carole
C
Li
Zuomei
Z
MacLeod
A Robert
AR
Besterman
Jeffrey M
JM
Delorme
Daniel
D
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
D000577:Amides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases