Cyclization-activated prodrugs. Synthesis, reactivity and toxicity of dipeptide esters of paracetamol

Dipeptide esters of paracetamol were prepared in high yields. These compounds are quantitatively hydrolyzed to paracetamol and corresponding 2,5-diketopiperazines at pH 7.4 and 37 degrees C. The reactivity is increased in sarcosine and proline peptides and decreased by bulky side chains at both the...

Full description

Bibliographic Details
Main Author: Santos, C (author)
Other Authors: Mateus, ML (author), dos Santos, AP (author), Moreira, R (author), de Oliveira, E (author), Gomes, P (author)
Format: article
Language:eng
Published: 2005
Subjects:
Química
Chemical sciences
Online Access:https://hdl.handle.net/10216/82058
Country:Portugal
Oai:oai:repositorio-aberto.up.pt:10216/82058
Description
Summary:Dipeptide esters of paracetamol were prepared in high yields. These compounds are quantitatively hydrolyzed to paracetamol and corresponding 2,5-diketopiperazines at pH 7.4 and 37 degrees C. The reactivity is increased in sarcosine and proline peptides and decreased by bulky side chains at both the N- and C-terminal residues of the dipeptide carrier. Moreover, dipeptide esters of paracetamol did not affect the levels of hepatic glutathione. Thus, dipeptides seem promising candidates as carriers for cyclization-activated prodrugs.

Similar Items