NEW DRUG FOR CHELATION THERAPY OF IRON OVERLOAD

THE RESEARCH IS DESIGNED TO DEVELOP AN IMPROVED SYNTHETIC METHOD FOR THE PRODUCTION OF A NEW BIOEFFICIENT DERIVATIVE OF AN ORALLY ACTIVE IRON CHELATOR FOR THE TREATMENT OF IRON OVERLOAD. IN PHASE I HUMAN TRIALS, THE PARENT DRUG (GIVEN ORALLY IN CAPSULES) PRODUCED AN AMOUNT OF IRON EXCRETION THAT WOULD BE CLINICALLY USEFUL IN THE TREATMENT OF NON- TRANSFUSION-DEPENDENT PATIENTS WITH IRON-LOADING ANEMIAS. THE BIOEFFICIENCY OF THE PARENT FORMULATION WAS MUCH LESS THAN THAT EXPECTED FROM ANIMAL STUDIES WITH THE PARENT DRUG GIVEN IN SOLUTION. HYPOTHESIZING THAT THE LIMITED BIOEFFICIENCY OBSERVED IN THE HUMAN STUDIES WAS THE RESULT OF THE POOR SOLUBILITY OF THE PARENT DRUG, WE HAVE DEVELOPED A PILOT-SCALE SYNTHESIS FOR THE PRODUCTION OF A NEW DERIVATIVE THAT IS MORE THAN 200-FOLD MORE WATER SOLUBLE. THIS NEW DRUG SHOULD SUBSTANTIALLY ENHANCE BIOEFFICIENCY AND MAKE THE CHELATOR CLINICALLY USEFUL IN THE TREATMENT OF TRANSFUSION-DEPENDENT PATIENTS. THE PHASE I PROJECT WILL DEVELOP A LARGER-SCALE METHOD OF SYNTHESIS OF THE NEW PRODRUG THAT WILL PERMIT THE PRODUCTION OF CLINICAL SUPPLIES FOR FURTHER HUMAN TRIALS DURING A PHASE II PROJECT.