Stereodefined and polyunsaturated inhibitors of histone deacetylase based on (2E,4E)-5-arylpenta-2,4-dienoic acid hydroxyamides

Charles M Marson; Nawal Serradji; Alphonso S Rioja; Sebastien P Gastaud; John P Alao; R Charles Coombes; David M Vigushin

doi:10.1016/j.bmcl.2004.03.012

Stereodefined and polyunsaturated inhibitors of histone deacetylase based on (2E,4E)-5-arylpenta-2,4-dienoic acid hydroxyamides

Bioorg Med Chem Lett. 2004 May 17;14(10):2477-81. doi: 10.1016/j.bmcl.2004.03.012.

Authors

Charles M Marson¹, Nawal Serradji, Alphonso S Rioja, Sebastien P Gastaud, John P Alao, R Charles Coombes, David M Vigushin

Affiliation

¹ Department of Chemistry, University College London, Christopher Ingold Laboratories, 20 Gordon Street, London WC1H OAJ, UK. [email protected]

PMID: 15109636
DOI: 10.1016/j.bmcl.2004.03.012

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amides / chemical synthesis
Amides / pharmacology
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Histone Deacetylase Inhibitors*
Humans
Hydroxamic Acids / chemical synthesis
Hydroxamic Acids / pharmacology*
Inhibitory Concentration 50
Stereoisomerism
Structure-Activity Relationship

Substances

Amides
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Hydroxamic Acids
oxamflatin