Coumarin-based prodrugs. Part 3: Structural effects on the release kinetics of esterase-sensitive prodrugs of amines

Bioorg Med Chem. 1998 Apr;6(4):417-26. doi: 10.1016/s0968-0896(98)00014-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Amines / metabolism*
  • Animals
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Coumarins / chemistry
  • Coumarins / metabolism*
  • Esterases / metabolism*
  • Half-Life
  • Kinetics
  • Liver / enzymology
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Pharmaceutic Aids / chemistry
  • Pharmaceutic Aids / metabolism*
  • Prodrugs / chemistry
  • Prodrugs / metabolism*
  • Spectrophotometry, Ultraviolet
  • Structure-Activity Relationship
  • Swine

Substances

  • Amines
  • Coumarins
  • Pharmaceutic Aids
  • Prodrugs
  • Esterases