Literature

Abstract

Novel indole-piperazine derivatives with a hydroxamic acid moiety were designed and synthesized as selective histone deacetylase 6 (HDAC6) inhibitors. In enzymatic assays, all compounds exhibited nanomolar IC50 values. N-hydroxy-4-((4-(7-methyl-1H-indole-3-carbonyl)piperazin-1-yl)methyl)benzamide, 9c, was the most potent HDAC6 inhibitor (IC50, 13.6 nM). In vitro, 9c induced neurite outgrowth of PC12 cells without producing toxic effects, better than Tubastatin A (Tub A). Additionally, 9c demonstrated blatant neuroprotective activity in PC12 cells against H2O2-induced oxidative damage. In western blot assay, 9c could increase the acetylation of α-tubulin in a dose-dependent manner.

DOI： 10.1016/j.bmcl.2023.129148

Discovery of indole-piperazine derivatives as selective histone deacetylase 6 inhibitors with neurite outgrowth-promoting activities and neuroprotective activities

Bioorganic & Medicinal Chemistry Letters 2023.0

Discovery of Benzylpiperazine Derivatives as CNS-Penetrant and Selective Histone Deacetylase 6 Inhibitors

ACS Medicinal Chemistry Letters 2022.0

Quinazolin-4-one Derivatives as Selective Histone Deacetylase-6 Inhibitors for the Treatment of Alzheimer’s Disease

Journal of Medicinal Chemistry 2013.0

Design and Synthesis of Mercaptoacetamides as Potent, Selective, and Brain Permeable Histone Deacetylase 6 Inhibitors

ACS Medicinal Chemistry Letters 2017.0

5-Aroylindoles Act as Selective Histone Deacetylase 6 Inhibitors Ameliorating Alzheimer’s Disease Phenotypes

Journal of Medicinal Chemistry 2018.0

Design, Synthesis, and Biological Evaluation of 2,4-Imidazolinedione Derivatives as HDAC6 Isoform-Selective Inhibitors