title: Stereodefined and polyunsaturated inhibitors of histone deacetylase based on (2E,4E)-5-arylpenta-2,4-dienoic acid hydroxyamides.
abstract: 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.
authors.affiliation: Department of Chemistry, University College London, Christopher Ingold Laboratories, 20 Gordon Street, London WC1H OAJ, UK. c.m.marson@ucl.ac.uk
authors.forename: Charles M
authors.initials: CM
authors.lastname: Marson
authors.forename: Nawal
authors.initials: N
authors.lastname: Serradji
authors.forename: Alphonso S
authors.initials: AS
authors.lastname: Rioja
authors.forename: Sebastien P
authors.initials: SP
authors.lastname: Gastaud
authors.forename: John P
authors.initials: JP
authors.lastname: Alao
authors.forename: R Charles
authors.initials: RC
authors.lastname: Coombes
authors.forename: David M
authors.initials: DM
authors.lastname: Vigushin
mesh_terms: 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
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C100692:oxamflatin