COUMARIN-BASED PRODRUGS - PART-3 - STRUCTURAL EFFECTS ON THE RELEASE KINETICS OF ESTERASE-SENSITIVE PRODRUGS OF AMINES

To study the structural effects on the release kinetics of a coumarin- based esterase-sensitive prodrug system, two series of compounds with varying structural features of the ester 'trigger' part and the amine 'drug' part were synthesized. The half-lives of the nine model prodrug s in the presence of porcine liver esterase ranged from about 2 min to 190 min. The steric bulkiness of the acyl group seems to have only a very minor effect on the half-lives of the esterase-triggered release of amines from the model prodrugs. The rate of the lactonization depen ds on the steric and electronic properties of the amine moiety. (C) 19 98 Elsevier Science Ltd. All rights reserved.