1. Spiro-1-benzofuranpiperidinylalkanoic acids as a novel and selective sphingosine S1P5 receptor agonist chemotype
- Author
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Axel Stoit, Sjoerd van Schaik, Josephus H. M. Lange, Annemieke Rensink, Adri van den Hoogenband, Chris G. Kruse, Hein K. A. C. Coolen, and Arnold P. den Hartog
- Subjects
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 - Abstract
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.
- Published
- 2018