title: Highly ligand efficient and selective N-2-(Thioethyl)picolinamide histone deacetylase inhibitors inspired by the natural product psammaplin A.
abstract: Novel picolinamide-based histone deacetylase (HDAC) inhibitors were developed, drawing inspiration from the natural product psammaplin A. We found that the HDAC potency and isoform selectivity provided by the oxime unit of psammaplin A could be reproduced by using carefully chosen heterocyclic frameworks. The resulting (hetero)aromatic amide based compounds displayed very high potency and isoform selectivity among the HDAC family, in addition to excellent ligand efficiency relative to previously reported HDAC inhibitors. In particular, the high HDAC1 isoform selectivity provided by the chloropyridine motif represents a valuable design criterion for the development of new lead compounds and chemical probes that target HDAC1.
authors.affiliation: Department of Chemistry, Imperial College London, London SW7 2AZ (UK).
authors.forename: Matthias G J
authors.initials: MG
authors.lastname: Baud
authors.forename: Patricia
authors.initials: P
authors.lastname: Haus
authors.forename: Thomas
authors.initials: T
authors.lastname: Leiser
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Meyer-Almes
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Fuchter
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D004220:Disulfides / Q000737:chemistry* / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D010848:Picolinic Acids / Q000737:chemistry* / Q000494:pharmacology*; D020033:Protein Isoforms / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000577:Amides; D004220:Disulfides; D056572:Histone Deacetylase Inhibitors; D010848:Picolinic Acids; D020033:Protein Isoforms; C098378:psammaplin A; D014443:Tyrosine; D006655:Histone Deacetylases; C003142:picolinamide