The present proposal is concerned with the synthesis of anticystinotic agents. Cystinosis is a rare, inborn, fatal, metabolic disorder resulting from the inability of the lysosomal tissues to clear cystine. Cystinosis is presently controlled by administration of cysteamine or phosphocysteamine. The repulsive odor of cysteamine frequently causes outright rejection by the patient. Although Phosphocysteamine is superior in this respect, it is not entirely odor free; both are inadequate due to the short duration of their activity and a limited ability to cross the blood-brain barrier.
The specific aims are:l) To synthesize a new, superior anticytinotic agent. Target compounds are: a) thiazolidine and thiazoline derivatives capable of releasing cysteamine """"""""in vivo"""""""" (pro-drug approach) and b) fatty chain substituted cysteamine derivatives capable of crossing the blood-barrier and alleviate CNS effects of cystinosis. Compounds of this type have also the potential to stimulate growth hormone release via somastatinergic blockade. Consequently, they may be beneficial to wound healing, normal growth, skin transplants, aging, and maintenance of correct body weight. 2) To develop and to standardize a manufacturing process for Phosphocysteamine on a larger scale in order to meet the growing demand and to comply with NDA requirements.
