Benzo[b]thiophene-based histone deacetylase inhibitors

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.

Graphical abstractBenzo[b]thienyl hydroxamic acids were identified via a targeted screen of small molecule hydroxamic acids. Various substitutions were explored in the benzo[b]thiophene C5- and C6-positions which lead to a consistent finding that a three-atom spacer in the C6-position yielded optimal HDAC1 inhibition and anti-proliferative activity.Figure optionsDownload full-size imageDownload as PowerPoint slide