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

Cyclization-activated Prodrugs

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; in revised form: 8 November 2007 / Accepted: 9 November 2007 / Published: 12 November 2007
(This article belongs to the Special Issue Prodrugs)
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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.

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MDPI and ACS Style

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

AMA Style

Gomes P, Vale N, Moreira R. Cyclization-activated Prodrugs. Molecules. 2007; 12(11):2484-2506.

Chicago/Turabian Style

Gomes, Paula; Vale, Nuno; Moreira, Rui. 2007. "Cyclization-activated Prodrugs." Molecules 12, no. 11: 2484-2506.

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