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
Journal of Medicinal Chemistry2005Vol. 48(16), pp. 5373–5377
Citations Over TimeTop 10% of 2005 papers
Rainer Albert, Klaus Hinterding, Volker Brinkmann, Danilo Guerini, Constanze Müller-Hartwieg, Helmut Knecht, Corinne Simeon, Markus Streiff, Trixie Wagner, Karl Welzenbach, Frédéric J. Zécri, Markus Zollinger, Nigel G. Cooke, Eric Francotte
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.
Related Papers
- → Role of the C8 gem-dimethyl group of bryostatin 1 on its unique pattern of biological activity(2012)25 cited
- → Synthesis and biological activity of aminophthalazines and aminopyridazines as novel inhibitors of PGE2 production in cells(2012)12 cited
- → Synthesis and biological activity of enantiomers of a conformationally restricted muscarone analog(1995)6 cited
- → Chemotactic Peptide Analogues. Synthesis and Chemotactic Activity of N‐Formyl‐Met‐Leu‐Phe Analogues Containing (S)‐Phenylalaninol Derivatives(1995)5 cited
- → New nonpeptide angiostensin II receptor antagonists. Synthesis, biological properties and structure-activity relationships of 3-substituted 2,6-dialkyl-4-(biphenyll)methylaminopyridine derivatives.(1994)1 cited