title: Benzo[b]thiophene-based histone deacetylase inhibitors.
abstract: Benzo[b]thienyl hydroxamic acids, a novel class of histone deacetylase (HDAC) inhibitors, were identified via a targeted screen of small molecule hydroxamic acids. Various substitutions were explored in the C5- and C6-positions of the benzo[b]thiophene core to characterize SAR and develop optimal inhibitors. It was determined that substitution at the C6-position of the benzo[b]thiophene core with a three-atom spacer yielded optimal HDAC1 inhibition and anti-proliferative activity in murine erythroleukemia (SC-9) cells.
authors.affiliation: Merck Research Laboratories, Department of Drug Design & Optimization, 33 Avenue Louis Pasteur, Boston, MA 02115, USA. David_Witter@merck.com
authors.forename: David J
authors.initials: DJ
authors.lastname: Witter
authors.forename: Sandro
authors.initials: S
authors.lastname: Belvedere
authors.forename: Liqiang
authors.initials: L
authors.lastname: Chen
authors.forename: J Paul
authors.initials: JP
authors.lastname: Secrist
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Mosley
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Miller
mesh_terms: D020650:Combinatorial Chemistry Techniques; D003198:Computer Simulation; D056572:Histone Deacetylase Inhibitors; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D056572:Histone Deacetylase Inhibitors; D013876:Thiophenes