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
Article Menu

Export Article

Open AccessReview
Molecules 2007, 12(11), 2484-2506; doi:10.3390/12112484

Cyclization-activated Prodrugs

Centro de Investigação em Química da Universidade do Porto, Departamento de Química, Faculdade de Ciências, Universidade do Porto, Porto, Portugal
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]   |  


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 View Full-Text
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 alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

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

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top