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Design, synthesis and biological evaluation of 4-methoxy diaryl isophthalates as antiplatelet agents
- Source :
- Medicinal Chemistry Research. 27:488-496
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- A series of 4-methoxy diphenyl isophthalates, which are the isosturctural analogs of picotamide, were designed and synthesized using the concept of isosterism. The structures of these new analogs were characterized by all means of spectroscopy, including 1H NMR, 13C NMR, and MS spectra. In vitro antiplatelet aggregation activities of these compounds were investigated by using Born’s test method. Among the 19 compounds tested for both ADP and collagen inducers, six of them (P216–P219 and P220–P221) were found to exhibit higher activity in vitro antiplatelet aggregation than Picotamide. In particular, the compound P220 bearing a nitrooxyl group showed the highest acitivity 72.1% (induced by collagen) and 72.5% (induced by ADP), with IC50 values of 0.30 μM/L induced by ADP (1.3 μM/L) and LD50 > 2500 mg/kg, could have dual mechanism of action. Evaluation of cytotoxic activity of the compounds against L929 cell line revealed that none of the compounds have significant cytotoxicity. Through the careful analysis of in vitro activity data, the SAR of these compounds was preliminarily deduced. The results of this study showed that 4-methoxy diaryl isophthalates derivatives are potential to become an antiplatelet aggregation agents.
- Subjects :
- 010405 organic chemistry
Chemistry
Stereochemistry
Organic Chemistry
Carbon-13 NMR
01 natural sciences
In vitro
0104 chemical sciences
010404 medicinal & biomolecular chemistry
Design synthesis
medicine
Proton NMR
Picotamide
Inducer
General Pharmacology, Toxicology and Pharmaceutics
Cytotoxicity
Biological evaluation
medicine.drug
Subjects
Details
- ISSN :
- 15548120 and 10542523
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Medicinal Chemistry Research
- Accession number :
- edsair.doi...........ef4634d3e3fb2583210df2ef70efc24b