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Review
. 2008 Mar 3;13(3):519-47.
doi: 10.3390/molecules13030519.

Prodrugs for amines

Ana L Simplício  1 , John M Clancy, John F Gilmer
Affiliations
Review

Prodrugs for amines

Ana L Simplício et al. Molecules. .

Abstract

The purpose of this work is to review the published strategies for the production of prodrugs of amines. The review is divided in two main groups of approaches: those that rely on enzymatic activation and those that take advantage of physiological chemical conditions for release of the drugs. A compilation of the most important approaches is presented in the form of a table, where the main advantages and disadvantages of each strategy are also referred.

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Figures

Scheme 1
Scheme 1
Tripartite prodrug system for tertiary amines (illustrated for fosphenytoin).
Scheme 2
Scheme 2
Hydrolysis of (acyloxy)alkyl carbamate and amine prodrugs.
Scheme 3
Scheme 3
Intramolecular acyl transfer in N-acyloxyalkoxycarbonyl derivatives of primary amines.
Scheme 4
Scheme 4
Generalised reduction pathway for nitro-heterocycles [55].
Scheme 5
Scheme 5
Mechanism of activation of 2-aminoaryl derivatives.
Scheme 6
Scheme 6
Activation of the 4-azidobenzyloxycarbonyl prodrug system.
Scheme 7
Scheme 7
Redox carrier system to the brain.
Scheme 8
Scheme 8
Metabolism of progabide.
Scheme 9
Scheme 9
Synthesis of N-Mannich bases.
Scheme 10
Scheme 10
Esterase sensitive N-Mannich bases of salicylamide as prodrugs for amines.
Scheme 11
Scheme 11
(Oxodioxolenyl)methyl carbamate prodrugs of amines: mechanism of base-catalysed cleavage.
Scheme 12
Scheme 12
Enzymatic hydrolysis of Prulifloxacin [95].
Scheme 13
Scheme 13
Stabilisation of enaminones.
Scheme 14
Scheme 14
Hydrolysis of enaminones.
Scheme 15
Scheme 15
"Trimethyl lock" prodrug system for amino drugs.
Figure 1
Figure 1
Tripartite "trimethyl lock" systems.
Scheme 16
Scheme 16
Coumarin-based esterase sensitive system for amino drugs.
Figure 2
Figure 2
THTT prodrug system for amines and amino acids.
Figure 3
Figure 3
Coumarin system applied to peptides.
Scheme 17
Scheme 17
Conversion of 2-pyrrolidinone to GABA.
See this image and copyright information in PMC

References

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