Design and synthesis of novel hybrid benzamide-peptide histone deacetylase inhibitors.

Abstract

We designed and synthesized a series of novel hybrid histone deacetylase inhibitors based on conjugation of benzamide-type inhibitors with either linear or cyclic peptides. Linear tetrapeptides (compounds 13 and 14), cyclic tetrapeptides (compounds 1 and 11), and heptanediamide-peptide conjugates (compounds 10, 12, 15 and 16) were synthesized through on-resin solid-phase peptide synthesis (SPPS). All compounds were found to be moderate HDAC1 and HDAC3 inhibitors, with IC(50) values ranging from 1.3 microM to 532 microM. Interestingly, compound 15 showed 19-fold selectivity for HDAC3 versus HDAC1.

DOI: 10.1016/j.bmcl.2009.03.085

Cite this paper

@article{Hu2009DesignAS, title={Design and synthesis of novel hybrid benzamide-peptide histone deacetylase inhibitors.}, author={Fang Hu and Chiyan James Chou and Joel M. Gottesfeld}, journal={Bioorganic & medicinal chemistry letters}, year={2009}, volume={19 14}, pages={3928-31} }