Presenter : Muhammad Khalifa
Mentor : Michael Haley
Major : Biochemistry
Poster 16
Myotonic dystrophy (DM) is the most common adult form of muscular dystrophy. Recently, the small molecule pentamidine has been shown to relieve symptoms of DM in cell models; however, pentamidine is an inadequate drug for DM because of toxicity and bioavailability problems. Analogs of pentamidine, generically termed amidines, have proven to be significant candidates in the search for an effective cure for DM. It is therefore important to have access to the widest possible range of amidine structures for study against symptoms of DM. Existing methods of synthesizing amidines have largely depended upon reactions with acidic con- ditions; features of these reactions have limited the accessible range of amidines, especially substituted amidines. Here we outline a new method of preparing substituted amidines using alkaline conditions that features shorter reaction times, better yields, and better compatibility with many of our compounds of interest. Through synthesis and NMR characterization, we explore the range of usable starting materials, test the method’s selectivity in the presence of competing reactions, and demonstrate its application to the synthesis of several novel compounds. This method makes possible a host of new substituted amidine compounds that could prove useful in the search for a cure for DM, and provides a new, potentially more efficient, synthetic path to unsubstituted amidines for the same purpose.