Synthesis and Biological Evaluation of a 5-6-5 Imidazole-Phenyl-Thiazole Based alpha-Helix Mimetic

The development of small molecules that disrupt protein-protein Interactions is a key goal in addressing a number of disease states. The cc-helix It, commonly found at protein Interaction interfaces and has been the focus of substantial small molecule mimetic efforts. One of the primary drawbacks of many small molecule alpha-helix mimetics is their hydrophobic core structures. To address this problem we have developed a novel scaffold based on a more water soluble 5-6-5 Imidazole-phenyl-thiazole core. An inhibitor of this class has been shown to disrupt the Cdc42/Dbs protein-protein Interaction at micromolar concentrations and may be useful in overcoming Cdc42-induced tumor resistance to anticancer therapies.