Sythesis of carporide Derivatives for Sodium-Proton Exchange Inhibition

Over 200,000 people in the United States are diagnosed annually with malignant brain tumors. Current therapeutic methods prove ineffective at treating this type of cancer due to the inability to selectively target cancer cells. Research has shown that brain cancer cells are heavily dependent on the sodium-proton exchanger (NHE) and sodium-calcium exchanger (NCX) due to their increased metabolic activity. Inhibiting these proteins disrupts pH and ion balances within cancer cells while leaving healthy cells unaffected, leading to selective glial cell death. Therefore, NHE and NCX inhibition allow for selective targeting of brain cancer cells. The challenge that remains in using these inhibitors as a treatment is effectively delivering them to poorly vascularized tissues. As part of our target-specific approach to treating brain cancer, we have synthesized analogs of cariporide, a potent NHE inhibitor, to address these challenges. The present thesis will discuss our efforts towards the preparation of our analogs.