title: Novel histone deacetylase 6 (HDAC6) selective inhibitors: a patent evaluation (WO2014181137).
abstract: Histone deacetylases (HDACs) are known to deacetylate histones and other proteins, which makes HDAC inhibitors able to affect cell survival, cell signaling, transport, and gene expression. Those effects have been associated to the therapeutic success of HDAC inhibitors. Class I-selective or pan-HDAC inhibitors have been approved for cancer therapy by the US Food and Drug Administration (FDA). Moreover, HDAC6 selective inhibitors entered phase I and II clinical trials for treating multiple myeloma. The development of potent and selective HDAC inhibitors is a hot topic in current drug discovery. Areas covered: The invention described in this patent (WO2014181137) is related to hydroxamic acid derivatives with inhibitory activity towards HDACs, their synthetic process and pharmaceutical formulations, as well as a method for treating patients suffering from a list of selected tumoral, inflammatory, cardiac and chronic disorders. Expert opinion: The compounds disclosed within this patent are selective against HDAC6 and their structure is related to tubastatin A, a known HDAC6 selective inhibitor. They are newly synthesized diarylamines showing an improved selectivity profile compared to other diarylamines under clinical investigation.
authors.affiliation: a School of Pharmaceutical Sciences , University of Geneva, University of Lausanne , Geneva , Switzerland.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Simões-Pires
authors.affiliation: b Institut de Chimie des Milieux et Matériaux de Poitiers, UMR CNRS 7285 , Poitiers , France.|c Réseau Epigénétique du Cancéropôle Grand Ouest , France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertrand
authors.affiliation: a School of Pharmaceutical Sciences , University of Geneva, University of Lausanne , Geneva , Switzerland.
authors.forename: Muriel
authors.initials: M
authors.lastname: Cuendet
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D015195:Drug Design; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000187:drug effects*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010330:Patents as Topic
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases
keywords: Diarylamine; HDAC inhibitor; HDAC6 selectivity; hydroxamic acid