Metabolic Considerations in Prodrug Design

Abstract

This review concentrates on prodrugs designed by pharmaceutical chemists to overcome biopharmaceutical or pharmacokinetic (essentially metabolic) problems encountered with active principles. The investigations presented in this review illustrate the types of problems pharmaceutical chemists have tried to solve and the metabolic, kinetic, or biopharmaceutical rationale behind these attempts. Although very little published information is available on pharmacokinetic methods useful in the study of prodrugs and on the regulatory requirements needed for prodrug development, the authors have tried to develop some general ideas that might be useful in this regard.

Cobaltocene-Induced Low-Temperature Radical Coupling Reactions in a Cobalt–Alkyne Series

“…To further expand the scope of the reaction, an intramolecular variant was explored in order to develop access to 1,5-cyclodecadiynes with acid-sensitive moieties located on the periphery of the aromatic rings. Given the structural proximity to the cytotoxic enediynes, radical cyclization products can provide a novel carbon framework in the development of the new generation of nontoxic prodrugs for cancer treatment. Dimethyl ether 15 was synthesized from the respective bis alcohol by treatment with methanol in the presence of BF 3 ·Me 2 O .…”

Planejamento, síntese e avaliação biológica de novos derivados da oxamniquina

“…-Sistemas de controle químico: aqueles no qual a taxa do fármaco liberado é predominantemente controlada pela taxa de degradação (Balant, Doelker, 1995). pode melhorar a solubilidade em água (Soyez et ai., 1996;Hoste et ai., 2000).…”

“…O desenvolvimento de pró-fármacos, na química medicinal, equivale ao desenvolvimento de grupos protetores na química orgânica. (Balant, Doelker, 1995). Normalmente a conversão do pró-fármaco ao fármaco protótipo dentro do organismo pode ocorrer por catálise enzimática e por variação de pH (Bundgaard, 1985;Balant, Doelker, 1995;Soyez et ai., 1996).…”

“…(Balant, Doelker, 1995). Normalmente a conversão do pró-fármaco ao fármaco protótipo dentro do organismo pode ocorrer por catálise enzimática e por variação de pH (Bundgaard, 1985;Balant, Doelker, 1995;Soyez et ai., 1996).…”