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 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.
Wang
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Department of Chemistry, North Carolina State University, Raleigh 27695-8204, USA. binghe_wang@ncsu.edu
Zhang
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Zheng
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Wang
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D000588:Amines / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003374:Coumarins / Q000737:chemistry / Q000378:metabolism*; D004950:Esterases / Q000378:metabolism*; D006207:Half-Life; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010592:Pharmaceutic Aids / Q000737:chemistry / Q000378:metabolism*; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013552:Swine
D000588:Amines; D003374:Coumarins; D010592:Pharmaceutic Aids; D011355:Prodrugs; D004950:Esterases