DEVELOPMENT OF ANTICYSTINOTIC AGENTS

THIS RESEARCH IS CONCERNED WITH ANTICYSTINOTIC AGENTS. CYSTINOSIS IS A FATAL METABOLIC DISORDER AFFLICTING 300 TO 400 CHILDREN NATIONWIDE. IT IS PRESENTLY CONTROLLED BY DAILY ADMINISTRATION OF CYSTEAMINE OR PHOSPHOCYSTEAMINE. THE REPULSIVE ODOR OF CYSTEAMINE BRINGS ABOUT AN OUTRIGHT REJECTION OF THIS MEDICATION. PHOSPHOCYSTEAMINE REPRESENTS A SIGNIFICANT IMPROVEMENT IN THIS RESPECT. IT IS, HOWEVER, NOT READILY AVAILABLE DUE TO LACK OF A SATISFACTORY MANUFACTURING PROCESS. IT IS PLANNED TO SYNTHESIZE ACID-LABILE CYCLIC CYSTEAMINE DERIVATIVES SUCH AS 2-THIAZOLINES AND THIAZOLIDINES. COMPOUNDS OF THIS TYPE ARE EXPECTED TO LIBERATE CYSTEAMINE WHEN ACTED UPON BY THE STOMACH ACID. A NUMBER OF COMPOUNDS HAVING A LONG ALKYL CHAIN ATTACHED TO THE CYSTEAMINE STRUCTURE WILL ALSO BE SYNTHESIZED. A LONGER ALKYL CHAIN IS KNOWN TO ABOLISH THE REPULSIVE STENCH OF THE LOWER ALKYL THIOLS. BECAUSE THIOCHOLINE IS ACTIVE, THE INTRODUCTION OF AN ALKYL GROUP INTO THE CYSTEAMINE MOIETY DOES NOT APPEAR TO IMPAIR ITS ANTICYSTINOTIC ACTIVITY. THE ANTICYSTINOTIC EFFICACY OF THE COMPOUNDS PREPARED WILL BE EVALUATED. IT IS ALSO PLANNED TO DEVELOP A REPRODUCIBLE, LARGER SCALE MANUFACTURING PROCESS FOR PHOSPHOCYSTEAMINE. AT PRESENT, PHOSPHOCYSTEAMINE CAN BE PRODUCED IN SMALL BATCHES ONLY, ANDMEDEA RESEARCH LABORATORIES, INC., HAS DIFFICULTIES SUPPLYING IT IN ADEQUATE QUANTITIES.