Santos Cledir, Mateus Maria Luísa, dos Santos Ana Paula, Moreira Rui, de Oliveira Eliandre, Gomes Paula
CIQUP, Departamento de Química, Faculdade de Ciências do Porto, P-4169-007 Porto, Portugal.
Bioorg Med Chem Lett. 2005 Mar 15;15(6):1595-8. doi: 10.1016/j.bmcl.2005.01.065.
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.
对乙酰氨基酚的二肽酯以高收率制备。这些化合物在pH 7.4和37℃下定量水解为对乙酰氨基酚和相应的2,5 - 二酮哌嗪。在肌氨酸和脯氨酸肽中反应性增加，而在二肽载体的N - 和C - 末端残基处的庞大侧链会使其反应性降低。此外，对乙酰氨基酚的二肽酯不影响肝脏谷胱甘肽水平。因此，二肽似乎是环化激活前药载体的有前景的候选物。
