Next Article in Journal
Synthesis and Molecular Structure of Ethyl [N-tosyl-(R)-prolyloxy]-2(S)-[4-cyano-8,8-ethylenedioxy-5-oxo-5,6,7,8-tetrahydroindolizin-3-yl] Acetate, a Key Intermediate in the Total Synthesis of (20S)-Camptothecins
Next Article in Special Issue
The Drug Release Profile from Calcium-induced Alginate Gel Beads Coated with an Alginate Hydrolysate
Previous Article in Journal
A Novel Synthesis of Bromobenzenes Using Molecular Bromine
Previous Article in Special Issue
Bioreversible Derivatives of Phenol. 2. Reactivity of Carbonate Esters with Fatty Acid-like Structures Towards Hydrolysis in Aqueous Solutions
Molecules 2007, 12(11), 2484-2506; doi:10.3390/12112484
Review

Cyclization-activated Prodrugs

1,* , 1 and 2
1 Centro de Investigação em Química da Universidade do Porto, Departamento de Química, Faculdade de Ciências, Universidade do Porto, Porto, Portugal 2 Centro de Estudos de Ciências Farmacêuticas, Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal
* Author to whom correspondence should be addressed.
Received: 6 October 2007 / Revised: 8 November 2007 / Accepted: 9 November 2007 / Published: 12 November 2007
(This article belongs to the Special Issue Prodrugs)
View Full-Text   |   Download PDF [167 KB, uploaded 18 June 2014]   |  

Abstract

Many drugs suffer from an extensive first-pass metabolism leading to druginactivation and/or production of toxic metabolites, which makes them attractive targets forprodrug design. The classical prodrug approach, which involves enzyme-sensitive covalentlinkage between the parent drug and a carrier moiety, is a well established strategy toovercome bioavailability/toxicity issues. However, the development of prodrugs that canregenerate the parent drug through non-enzymatic pathways has emerged as an alternativeapproach in which prodrug activation is not influenced by inter- and intraindividualvariability that affects enzymatic activity. Cyclization-activated prodrugs have beencapturing the attention of medicinal chemists since the middle-1980s, and reached maturityin prodrug design in the late 1990s. Many different strategies have been exploited in recentyears concerning the development of intramoleculary-activated prodrugs spanning fromanalgesics to anti-HIV therapeutic agents. Intramolecular pathways have also a key role intwo-step prodrug activation, where an initial enzymatic cleavage step is followed by acyclization-elimination reaction that releases the active drug. This wor
Keywords: Cyclization; prodrugs; peptides; intramoleculary-activated prodrugs; two-step activation. Cyclization; prodrugs; peptides; intramoleculary-activated prodrugs; two-step activation.
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
SciFeed

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote |
RIS
MDPI and ACS Style

Gomes, P.; Vale, N.; Moreira, R. Cyclization-activated Prodrugs. Molecules 2007, 12, 2484-2506.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert