Treatment of Type II Diabetes: Synthesis and Analysis of Five Analogs of Compound NEt-4IB that Target the Retinoid-X-Receptor

This project details the synthesis and analysis of five analogs of model compound NEt-4IB (6-[ethyl(4-isobutoxy-3-isopropylphenyl)amino]nicotinic acid), that target the retinoid-X-receptor (RXR). These molecules were synthesized by substituting, adding, or removing substituents in the nitrogen-containing ring of NEt-4IB. The parent compound is a RXR partial agonist and has proven to be effective in the treatment of type II diabetes without the unwanted side effects seen with full agonists. Many of the current drugs used to treat type II diabetes are accompanied by adverse effects including increased triglyceride levels, weight gain, and hypoglycemia. Biological evaluation with KK-Ay (obese diabetic) model mice indicates that NEt-4IB may even be more effective than current drugs on the market, like pioglitazone. As a result, it is predicted that due to such structural similarity, the analogs synthesized for this work will perform equally, if not better than, NEt-4IB.