Potent histone deacetylase inhibitors derived from 4-(aminomethyl)-N-hydroxybenzamide with high selectivity for the HDAC6 isoform

…, K Garcia, K Gigstad, A Gould, J Gutierrez…

Index: Blackburn, Christopher; Barrett, Cynthia; Chin, Janice; Garcia, Kris; Gigstad, Kenneth; Gould, Alexandra; Gutierrez, Juan; Harrison, Sean; Hoar, Kara; Lynch, Chrissie; Rowland, R. Scott; Tsu, Chris; Ringeling, John; Xu, He Journal of Medicinal Chemistry, 2013 , vol. 56, # 18 p. 7201 - 7211

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Citation Number: 16

Abstract

A screen for HDAC6 inhibitors identified acyl derivatives of 4-(aminomethyl)-N- hydroxybenzamide as potent leads with unexpected selectivity over the other subtypes. We designed and synthesized constrained heterocyclic analogues such as tetrahydroisoquinolines that show further enhanced HDAC6 selectivity and inhibitory activity in cellular assays. Selectivity may be attributed to the benzylic spacer more effectively ...