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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; in revised form: 8 November 2007 / Accepted: 9 November 2007 / Published: 12 November 2007
(This article belongs to the Special Issue Prodrugs
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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Cite This Article
MDPI and ACS Style
Gomes, P.; Vale, N.; Moreira, R. Cyclization-activated Prodrugs. Molecules 2007, 12, 2484-2506.
Gomes P, Vale N, Moreira R. Cyclization-activated Prodrugs. Molecules. 2007; 12(11):2484-2506.
Gomes, Paula; Vale, Nuno; Moreira, Rui. 2007. "Cyclization-activated Prodrugs." Molecules 12, no. 11: 2484-2506.