Novel histone deacetylase inhibitors: N-hydroxycarboxamides possessing a terminal bicyclic aryl group

Utilizing tranexamic acid as a starting material, a series of N-hydroxycarboxamides were synthesized in order to seek new histone deacetylase (HDAC) inhibitors. Further structure optimization involving the replacement of the 1,4-cyclohexylene group with the 1,4-phenylene group yielded the promising HDAC inhibitors which possess a terminal bicyclic aryl amide. Synthesis of the promising histone deacetylase inhibitors including 10a and 10e is reported. The terminal bicyclic aryl amide groups of these compounds played an important role in increment of their inhibitory activities.