Furanonyl amino acid derivatives as hemostatic drugs: design, synthesis and hemostasis performance

Using 3,4-dihalo-2(5 H )-furanones and easily available hemostatic drugs, such as tranexamic acid (TA), 4-aminomethylbenzoic acid (ABA), aminocaproic acid (AA) as starting materials, serial multi-functional molecules 2(5 H )-furanonyl amino acids are designed by the combination of different pharmaco...

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Bibliographic Details
Published in:Amino acids 2022-07, Vol.54 (7), p.989-999
Main Authors: Wang, Neng, Lin, Jian-Yun, Luo, Shi-He, Zhou, Yong-Jun, Yang, Kai, Chen, Ren-Hong, Yang, Guo-Xian, Wang, Zhao-Yang
Format: Article
Language:English
Subjects:
Abscisic acid
Amino acids
Analytical Chemistry
Antifibrinolytic agents
Biochemical Engineering
Biochemistry
Biomedical and Life Sciences
Dichloromethane
Drug development
Drugs
Ethanol
Hemorrhage
Hemostasis
Hemostatics
Infrared spectroscopy
Life Sciences
Mass spectra
Model testing
Neurobiology
NMR
Nuclear magnetic resonance
Original Article
Performance evaluation
Pharmacophores
Proteomics
Room temperature
Spectrum analysis
Transition metals
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Summary:Using 3,4-dihalo-2(5 H )-furanones and easily available hemostatic drugs, such as tranexamic acid (TA), 4-aminomethylbenzoic acid (ABA), aminocaproic acid (AA) as starting materials, serial multi-functional molecules 2(5 H )-furanonyl amino acids are designed by the combination of different pharmacophores, and successfully synthesized by a transition metal-free Michael addition–elimination reaction. The reaction is carried out under mild conditions with ethanol-dichloromethane as solvent and only stirring at room temperature for 24 h, and the yield can be up to 91%. All products are well characterized by infrared spectroscopy (IR), nuclear magnetic resonance (NMR), high-resolution mass spectra (HRMS). Ten typical target compounds among them are selected out for the experiments of hemostasis performance by the evaluation of in vitro clot formation model and liver hemorrhage model. The test results show that, their hemostasis effect is better than the original drugs. Especially the target compound G , a TA derivative from 5-borneoloxy-3,4-dibromo-2(5 H )-furanone, has the best hemostasis effect among all the tested compounds. These obtained target molecules are expected to be used as multi-functional hemostatic drugs.
ISSN:0939-4451
1438-2199
DOI:10.1007/s00726-022-03155-3