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.
Dai
Yujia
Y
Cancer Research, Abbott Laboratories, Dept. R47J, Bldg. AP10, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA. yujia.dai@abbott.com
Guo
Yan
Y
Guo
Jun
J
Pease
Lori J
LJ
Li
Junling
J
Marcotte
Patrick A
PA
Glaser
Keith B
KB
Tapang
Paul
P
Albert
Daniel H
DH
Richardson
Paul L
PL
Davidsen
Steven K
SK
Michaelides
Michael R
MR
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