Stereodefined and polyunsaturated inhibitors of histone deacetylase based on (2E,4E)-5-arylpenta-2,4-dienoic acid hydroxyamides.
Syntheses of (2E,4E)-5-arylpenta-2,4-dienoic acid hydroxyamides are described, some of which are potent inhibitors of histone deacetylase, a double bond conferring more than a 10-fold increase in potency compared with the triple bond analogue oxamflatin. Variation of substituents on the aromatic ring has a marked effect on potency, in vitro IC(50) values down to 50 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
Serradji
Nawal
N
Rioja
Alphonso S
AS
Gastaud
Sebastien P
SP
Alao
John P
JP
Coombes
R Charles
RC
Vigushin
David M
DM
D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000577:Amides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C100692:oxamflatin