Structure-activity relationships of aryloxyalkanoic acid hydroxyamides as potent inhibitors of histone deacetylase.
Syntheses of aryloxyalkanoic acid hydroxyamides are described, all of which are potent inhibitors of histone deacetylase, some being more potent in vitro than trichostatin A (IC(50)=3 nM). Variation of the substituents on the benzene ring as well as fusion of a second ring have marked effects on potency, in vitro IC(50) values down to 1 nM being obtained.
Marson
Charles M
CM
Department of Chemistry, University College London, Christopher Ingold Laboratories, 20 Gordon Street, London WC1H OAJ, UK. c.m.marson@ucl.ac.uk
Mahadevan
Thevaki
T
Dines
Jon
J
Sengmany
Stéphane
S
Morrell
James M
JM
Alao
John P
JP
Joel
Simon P
SP
Vigushin
David M
DM
Charles Coombes
R
R
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000737:chemistry; D006801:Humans; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000577:Amides; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases