Chinese Journal of Organic Chemistry >
Design, Synthesis and Biological Activity of Dipeptide Derivatives Bearing Uracil Unit
Received date: 2018-11-30
Revised date: 2019-01-26
Online published: 2019-02-19
Supported by
Project supported by the National Natural Science Foundation of China (No. 21542003) and the Natural Science Foundation of Chongqing City (No. cstc2016jcyjA0421).
In order to explore a new type of anti-diabetic molecules, dipeptide derivatives containing uracil structural units were designed. The key intermediate S-thymine-L-cysteine (IM-2) was obtained from uracil, paraformaldehyde and cysteine through two step reactions, and then 16 dipeptide derivatives were successfully synthesized through amino protection, carboxylation and amino acid coupling. All new compounds have been characterized by 1H NMR, 13C NMR and HRMS, and the peroxisome proliferator response element (PPRE) activated activity, α-glucosidase-rat inhibitory activity and dipeptidyl peptidase-4 (DPP-4) inhibitory activity were screened for all target molecules. The results showed that these molecules had weak above-mentioned activities, meanwhile the change trend of α-glucosidase-rat inhibitory activity of these molecules is opposite to that of PPRE agonistic activity and DPP-4 inhibitory activity. It maybe provides an idea for the research of designing novel polypeptide multi-target drugs.
Tang Xuemei , Fan Li , Zhang Zechao , Yang Dacheng . Design, Synthesis and Biological Activity of Dipeptide Derivatives Bearing Uracil Unit[J]. Chinese Journal of Organic Chemistry, 2019 , 39(5) : 1460 -1468 . DOI: 10.6023/cjoc201811040
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