Design and synthesis of novel hybrid benzamide-peptide histone deacetylase inhibitors.
作者信息
Hu Fang, Chou C James, Gottesfeld Joel M
机构信息
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
出版信息
Bioorg Med Chem Lett. 2009 Jul 15;19(14):3928-31. doi: 10.1016/j.bmcl.2009.03.085. Epub 2009 Mar 25.
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.
摘要
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