Novel Immunomodulator FTY720 Is Phosphorylated in Rats and Humans To Form a Single Stereoisomer. Identification, Chemical Proof, and Biological Characterization of the Biologically Active Species and Its Enantiomer
| Autor: | Eric Francotte, Danilo Guerini, Markus Streiff, Markus Zollinger, Karl Welzenbach, Rainer Albert, Klaus Hinterding, Trixie Wagner, Helmut Knecht, Nigel Graham Cooke, Frédéric Zecri, Corinne Simeon, Constanze Müller-Hartwieg, Volker Brinkmann |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
Stereochemistry Stereoisomerism CHO Cells Crystallography X-Ray Chemical synthesis Radioligand Assay Structure-Activity Relationship chemistry.chemical_compound Cricetulus Adjuvants Immunologic Sphingosine Cricetinae Drug Discovery Animals Humans Structure–activity relationship Phosphorylation Rats Wistar Derivatization Chromatography High Pressure Liquid Fingolimod Hydrochloride Chemistry Enantioselective synthesis Biological activity Organophosphates Rats Receptors Lysosphingolipid Propylene Glycols Molecular Medicine Enantiomer Ex vivo |
| Zdroj: | Journal of Medicinal Chemistry. 48:5373-5377 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | In vivo phosphorylation of FTY720 (1) in rats and humans resulted exclusively in the biologically active (S)-configured enantiomer, which was proven by an ex vivo o-phthaldialdehyde derivatization protocol especially elaborated for phosphates of 1. Starting from the prochiral amino alcohol 1, racemic and enantiomerically pure phosphates of 1 were synthesized. Pure enantiomers were obtained after purification of a partially protected key intermediate on an enantioselective support. The absolute stereochemistry was determined by X-ray diffraction. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|