Chapter 8. The Hydrolysis of Carboxylic Acid Ester Prodrugs

  1. Prof. Bernard Testa and
  2. Dr. Joachim M. Mayer

Published Online: 9 NOV 2006

DOI: 10.1002/9783906390444.ch8

Hydrolysis in Drug and Prodrug Metabolism: Chemistry, Biochemistry, and Enzymology

Hydrolysis in Drug and Prodrug Metabolism: Chemistry, Biochemistry, and Enzymology

How to Cite

Testa, B. and Mayer, J. M. (2003) The Hydrolysis of Carboxylic Acid Ester Prodrugs, in Hydrolysis in Drug and Prodrug Metabolism: Chemistry, Biochemistry, and Enzymology, Verlag Helvetica Chimica Acta, Zürich. doi: 10.1002/9783906390444.ch8

Author Information

  1. Institute of Medicinal Chemistry, School of Pharmacy, University of Lausanne, CH-1015 Lausanne, Switzerland

Publication History

  1. Published Online: 9 NOV 2006
  2. Published Print: 17 JUN 2003

ISBN Information

Print ISBN: 9783906390253

Online ISBN: 9783906390444

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Keywords:

  • hydrolysis;
  • drug metabolism;
  • prodrug metabolism;
  • carboxylic acid ester prodrugs;
  • simple or functionalized alkyl pro-moiety;
  • prodrugs of active carboxylic acids;
  • incorporate fragmentable pro-moiety;
  • active carboxylic acids esterified with a phenol or hydroxylamine;
  • prodrugs of active alcohols;
  • prodrugs of active phenols;
  • lactones as prodrugs;
  • prodrugs of active amines;
  • prodrugs of active amides;
  • macromolecular prodrugs

Summary

This chapter contains sections titled:

  • Introduction

  • Prodrugs of Active Carboxylic Acids That Incorporate a Simple or Functionalized Alkyl Pro-Moiety

    • Prodrugs That Incorporate a Simple Alkyl Pro-Moiety

      • Ethyl Ester

      • Other Alkyl Esters

    • Prodrugs That Incorporate an Oxyalkyl, Hydroxyalkyl, or Arylalkyl Pro-Moiety

    • Carboxylic Acid Esters That Incorporate a Carbamoylmethyl, Aminoalkyl, or Amidoalkyl Pro-Moiety

      • Carbamoylmethyl Esters

      • Aminoalkyl Esters

      • Amidoalkyl Esters

    • Quantitative Structure–Metabolism Relationships in Prodrug Design

    • Carboxylic Acid Esters of Acylglycerols and Bis(acyl-amino)propan-2-ols

      • Hybrid Triglycerides

      • Hybrid Pseudolipid Analogues

  • Prodrugs of Active Carboxylic Acids That Incorporate Fragmentable Pro-Moiety

    • Glycolic Acid Esters

    • Prodrugs That Incorporate an (Acyloxy)alkyl or [(Alkoxycarbonyl)oxy]methyl Pro-Moiety

      • (Acyloxy)alkyl Esters

      • [(Alkoxycarbonyl)oxy]methyl Esters

    • Prodrugs That Incorporate an Amidomethyl, an Aminomethyl, or Another Fragmentable Pro-Moiety That Contains an Amino Group

    • Prodrugs That Incorporate an (Oxodioxolyl)methyl Pro-Moiety

  • Prodrugs of Active Carboxylic Acids Esterified with a Phenol or Hydroxylamine

    • Carboxylic Acid Esters of Phenols

    • Carboxylic Acid Esters of Hydroxylamines

  • Prodrugs of Active Alcohols and Phenols

    • Prodrugs That Incorporate an Alkanoyl Pro-Moiety

      • Acetic Acid Esters

      • Unbranched Alkanoic Acid Esters

      • Branched Alkanoic Acid Esters

      • Cycloalkanoic Acid Esters

    • Reactions of Intramolecular Acyl Transfer

    • Prodrugs That Incorporate an Aromatic Acyl Pro-Moiety

    • Prodrugs That Incorporate an Oxygenated Alkanoyl Pro-Moiety

    • Prodrugs That Incorporate an Amino Acyl Pro-Moiety

      • Esters of a-Amino Acids

      • Esters of Other Amino Acids

    • Prodrugs That Incorporate a Fragmentable Acyl Pro-Moiety

      • O-[(Acyloxy)methyl] Derivatives

      • Alkoxycarbonyl Derivatives

      • Carbamic Acid Esters

    • Cyclization-Activated Carboxylic Acid Ester Prodrugs

      • Nucleophilic Attack by a Basic Group

      • Intramolecular Attack by an Anionic N-Atom

      • Intramolecular Attack by a Carboxylate Group

      • Intramolecular Attack by a Hydroxy Group

    • Prodrugs That Incorporate a 1,4-Dihydropyridine Pro-Pro-Moiety

  • Lactones as Prodrugs

  • Prodrugs of Active Amines and Amides

    • Alkyl and Aryl Carbamates

    • (Acyloxy)methyl Carbamates

    • N-[(Acyloxy)methyl] Derivatives

      • Cleavage of the N-(Hydroxymethyl) Intermediate

      • Simple N-[(Acyloxy)methyl] Derivatives

      • Complex N-[(Acyloxy)methyl] Derivatives

    • Cyclization-Activated Double Prodrugs of Amines and Peptides

    • Special Cases

  • Macromolecular Prodrugs