Spiro-1-benzofuranpiperidinylalkanoic acids as a novel and selective sphingosine S1P5 receptor agonist chemotype
| Autor: | Axel Stoit, Sjoerd van Schaik, Josephus H. M. Lange, Annemieke Rensink, Adri van den Hoogenband, Chris G. Kruse, Hein K. A. C. Coolen, Arnold P. den Hartog |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Agonist medicine.drug_class Clinical Biochemistry Pharmaceutical Science Pharmacology 01 natural sciences Biochemistry Compound 32 03 medical and health sciences chemistry.chemical_compound Oral administration Drug Discovery medicine Structure–activity relationship Homology modeling Receptor Molecular Biology Sphingosine 010405 organic chemistry Organic Chemistry 0104 chemical sciences Bioavailability 030104 developmental biology chemistry Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 28:459-465 |
| ISSN: | 0960-894X |
| Popis: | The synthesis and SAR of a novel class of spirobenzofuranpiperidinyl-derived alkanoic acids 6-34 as sphingosine S1P5 receptor agonists are described. The target compounds generally elicit high S1P5 receptor agonistic potencies and in general are selective against both S1P1 and S1P3 receptor subtypes. The key compound 32 shows a high bioavailability of 73% and a CNS/plasma ratio of 0.8 after oral administration in rats. |
| Databáze: | OpenAIRE |
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