Design, synthesis, and in vitro bioactivity evaluation of fluorine-containing analogues for sphingosine-1-phosphate 2 receptor
| Autor: | Robyn S. Klein, Zhude Tu, Zonghua Luo, Hui Liu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Pharmaceutical Science chemistry.chemical_element 01 natural sciences Biochemistry Article chemistry.chemical_compound Drug Discovery Humans Potency Sphingosine-1-phosphate Receptor Sphingosine-1-Phosphate Receptors Molecular Biology S1PR1 S1PR2 010405 organic chemistry Chemistry Organic Chemistry Fluorine In vitro 0104 chemical sciences 010404 medicinal & biomolecular chemistry Molecular Medicine Selectivity |
| Zdroj: | Bioorg Med Chem |
| ISSN: | 0968-0896 |
| Popis: | Twenty eight new aryloxybenzene analogues were synthesized and their in vitro binding potencies toward S1PR2 were determined using a [32P]S1P competitive binding assay. Out of these new analogues, three compounds, 28c (IC50 = 29.9 ± 3.9 nM), 28e (IC50 = 14.6 ± 1.5 nM), and 28g (IC50 = 38.5 ± 6.3 nM) exhibited high binding potency toward S1PR2 and high selectivity over the other four receptor subtypes (S1PR1, 3, 4, and 5; IC50 > 1000 nM). Each of the three potent compounds 28c, 28e, and 28g contains a fluorine atom that will allow to develop F-18 labeled PET radiotracers for imaging S1PR2. |
| Databáze: | OpenAIRE |
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