摘要
目的为了改善缬沙坦的口服生物利用度,基于寡肽转运体(oligopeptide transporter,Pep T)的转运特点,设计并合成基于寡肽转运体的缬沙坦拟肽系列前药。方法基于寡肽转运体底物模型和缬沙坦分子结构,设计12个缬沙坦拟肽前药;以Trt-缬沙坦和带保护基的氨基酸原料,经缩合、脱保护得到2个缬沙坦氨基酸酯;以带保护基的不同氨基酸为原料,缩合得系列二肽化合物,然后分别与Trt-缬沙坦经缩合、脱保护得到10个缬沙坦二肽酯。结果合成了12个基于寡肽转运体的缬沙坦拟肽前药,目标化合物与关键中间体的化学结构经1H-NMR、MS确证。结论基于Pep T的底物特征,设计并合成了12个缬沙坦拟肽前药,为该类前药的深入研究奠定基础。
Objective To study the design and synthesis of valsartan peptidomimetic prodrugs based on oligopeptide transporter（Pep T）,with the aim of improving the intestinal absorption of valsartan.Methods Tw elve of valsartan peptidomimetic prodrugs were designed based on the molecular structure of valsartan and the substrate model of oligopeptide transporter.Valsartan amino acid esters were synthesized by condensation,followed by deprotection,then the intermediate condensed with Trt-valsartan,follow ed by deprotection to give valsartan dipeptide esters.Results Twelve valsartan peptidomimetic prodrugs were synthesized,and the chemical structures of targeting compounds and key intermediates were confirmed by 1H-NMR and MS spectra.Conclusions Twelve valsartan peptidomimetic prodrugs were designed and synthesized based on the characteristics of Pep T substrates,which might provide proof for the further investigation of the similar prodrugs.
出处
《沈阳药科大学学报》
CAS
CSCD
北大核心
2014年第12期955-961,共7页
Journal of Shenyang Pharmaceutical University
基金
吉林化工学院科技计划项目(201350)
关键词
寡肽转运体
缬沙坦
设计
合成
oligopeptide transporter
valsartan
design
synthesis
