Succinimide hydroxamic acids as potent inhibitors of histone deacetylase (HDAC).
A series of succinimide hydroxamic acids was prepared and evaluated in vitro for HDAC inhibition and tumor cell antiproliferation. While the original macrocyclic analogue 6 was quite potent in both assays, several appropriately substituted non-macrocyclic succinimides, such as 23, were equipotent.
Curtin
Michael L
ML
Cancer Research Area, Abbott Laboratories, Dept. 47J, Bldg. AP10, 100 Abbott Park Road, Abbott Park, IL 60064, USA. mike.curtin@abbott.com
Garland
Robert B
RB
Heyman
H Robin
HR
Frey
Robin R
RR
Michaelides
Michael R
MR
Li
Junling
J
Pease
Lori J
LJ
Glaser
Keith B
KB
Marcotte
Patrick A
PA
Davidsen
Steven K
SK
D000596:Amino Acids / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D007202:Indicators and Reagents; D020014:K562 Cells; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007202:Indicators and Reagents; D013388:Succinimides; D006655:Histone Deacetylases