Abstract
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 prodrugs 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 depends on the steric and electronic properties of the amine moiety.
Original language | English (US) |
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Pages (from-to) | 417-426 |
Number of pages | 10 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 6 |
Issue number | 4 |
DOIs | |
State | Published - Apr 1998 |
Externally published | Yes |
Keywords
- Coumarin
- Coumarinic acid
- Esterase
- Prodrug
- Structural effect
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry