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
- 9 July 2005
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 48 (16) , 5373-5377
- https://doi.org/10.1021/jm050242f
Abstract
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.Keywords
This publication has 9 references indexed in Scilit:
- Mice Deficient in Sphingosine Kinase 1 Are Rendered Lymphopenic by FTY720Journal of Biological Chemistry, 2004
- FTY720: Sphingosine 1-Phosphate Receptor-1 in the Control of Lymphocyte Egress and Endothelial Barrier FunctionAmerican Journal of Transplantation, 2004
- Phosphorylation of the Immunomodulatory Drug FTY720 by Sphingosine KinasesJournal of Biological Chemistry, 2003
- Alteration of Lymphocyte Trafficking by Sphingosine-1-Phosphate Receptor AgonistsScience, 2002
- Ring-chain tautomerism and other versatile behaviour of 1,4-diimino- and 1,2-phenylene derivatives of some C-substituted serinolsTetrahedron, 2002
- FTY720: ALTERED LYMPHOCYTE TRAFFIC RESULTS IN ALLOGRAFT PROTECTIONTransplantation, 2001
- Synthesis and Immunosuppressive Activity of 2-Substituted 2-Aminopropane-1,3-diols and 2-AminoethanolsJournal of Medicinal Chemistry, 2000
- A High-Performance Liquid Chromatographic Method to Measure Sphingosine 1-Phosphate and Related Compounds from Sphingosine Kinase Assays and Other Biological SamplesAnalytical Biochemistry, 2000
- Synthesis and biological evaluation of 2,2-disubstituted 2-aminoethanols: analogues of FTY720Bioorganic & Medicinal Chemistry Letters, 1998