Synthesis of 7200 small molecules based on a substructural analysis of the histone deacetylase inhibitors trichostatin and trapoxin

被引：137

作者：

Sternson, SM ^{[1
]}

Wong, JC ^{[1
]}

Grozinger, CM ^{[1
]}

Schreiber, SL ^{[1
]}

机构：

[1] Harvard Univ, Howard Hughes Med Inst, Dept Chem & Biol Chem, Inst Chem & Cell Biol, Cambridge, MA 02138 USA

来源：

ORGANIC LETTERS | 2001年 / 3卷 / 26期

关键词：

D O I：

10.1021/ol016915f

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

[GRAPHICS] Seventy-two hundred potential inhibitors of the histone deacetylase (HDAC) enzyme family, based on a 1,3-dioxane diversity structure, were synthesized on polystyrene macrobeads. The compounds were arrayed for biological assays in a "one bead-one stock solution" format. Metal-chelating functional groups were used to direct the 1,3-dioxanes to HDAC enzymes, which are zinc hydrolases. Representative structures from this library were tested for inhibitory activity and the 1,3-dioxane structure was shown to be compatible with HDAC inhibition.

引用

页码：4239 / 4242

页数：4

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