Significant effort is being made to understand the role of HDAC isotypes in human cancer and to develop antitumor agents with better therapeutic windows. A part of this endeavor was the exploration of the 14 Å internal cavity adjacent to the enzyme catalytic site, which led to the design and synthesis of compound 4 with the unusual bis (aryl)-type pharmacophore. SAR studies around this lead resulted in optimization to potent, selective, ...
