Indole amide hydroxamic acids as potent inhibitors of histone deacetylases.
A series of hydroxamic acid-based HDAC inhibitors with an indole amide residue at the terminus have been synthesized and evaluated. Compounds with a 2-indole amide moiety have been found as the most active inhibitors among the different regioisomers. Introduction of substituents on the indole ring further improved the potency and generated a series of very potent inhibitors with significant antiproliferative activity. A representative compound in the series, 7b, has been found to be orally active in tumor growth inhibition model.
Cancer Research, Abbott Laboratories, Dept. R47J, Bldg. AP10, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA. yujia.dai@abbott.com
Yujia
Y
Dai
Yan
Y
Guo
Jun
J
Guo
Lori J
LJ
Pease
Junling
J
Li
Patrick A
PA
Marcotte
Keith B
KB
Glaser
Paul
P
Tapang
Daniel H
DH
Albert
Paul L
PL
Richardson
Steven K
SK
Davidsen
Michael R
MR
Michaelides
D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000577:Amides; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; C030374:indole