Literature DB >> 16078855

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.

Rainer Albert1, Klaus Hinterding, Volker Brinkmann, Danilo Guerini, Constanze Müller-Hartwieg, Helmut Knecht, Corinne Simeon, Markus Streiff, Trixie Wagner, Karl Welzenbach, Frédéric Zécri, Markus Zollinger, Nigel 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.

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Year:  2005        PMID： 16078855     DOI： 10.1021/jm050242f

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  37 in total

Review 1.  A mechanistically novel, first oral therapy for multiple sclerosis: the development of fingolimod (FTY720, Gilenya).

Authors:  Jerold Chun; Volker Brinkmann
Journal:  Discov Med       Date:  2011-09       Impact factor: 2.970

Review 2.  Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis.

Authors:  Volker Brinkmann; Andreas Billich; Thomas Baumruker; Peter Heining; Robert Schmouder; Gordon Francis; Shreeram Aradhye; Pascale Burtin
Journal:  Nat Rev Drug Discov       Date:  2010-10-29       Impact factor: 84.694

3.  Immunomodulator FTY720 induces myofibroblast differentiation via the lysophospholipid receptor S1P3 and Smad3 signaling.

Authors:  Christina D Keller; Pilar Rivera Gil; Markus Tölle; Markus van der Giet; Jerold Chun; Heinfried H Radeke; Monika Schäfer-Korting; Burkhard Kleuser
Journal:  Am J Pathol       Date:  2007-01       Impact factor: 4.307

4.  Chiral vinylphosphonate and phosphonate analogues of the immunosuppressive agent FTY720.

Authors:  Xuequan Lu; Chaode Sun; William J Valentine; E Shuyu; Jianxiong Liu; Gabor Tigyi; Robert Bittman
Journal:  J Org Chem       Date:  2009-04-17       Impact factor: 4.354

5.  Stereochemistry-activity relationship of orally active tetralin S1P agonist prodrugs.

Authors:  Bin Ma; Kevin M Guckian; Edward Yin-Shiang Lin; Wen-Cherng Lee; Daniel Scott; Gnanasambandam Kumaravel; Timothy L Macdonald; Kevin R Lynch; Cheryl Black; Sowmya Chollate; Kyungmin Hahm; Gregg Hetu; Ping Jin; Yi Luo; Ellen Rohde; Anthony Rossomando; Robert Scannevin; Joy Wang; Chunhua Yang
Journal:  Bioorg Med Chem Lett       Date:  2010-02-06       Impact factor: 2.823

6.  Endocytosis of Ligand-Activated Sphingosine 1-Phosphate Receptor 1 Mediated by the Clathrin-Pathway.

Authors:  Patrick M Reeves; Yuan-Lin Kang; Tom Kirchhausen
Journal:  Traffic       Date:  2015-12-09       Impact factor: 6.215

7.  The Concise Guide to PHARMACOLOGY 2013/14: G protein-coupled receptors.

Authors:  Stephen P H Alexander; Helen E Benson; Elena Faccenda; Adam J Pawson; Joanna L Sharman; Michael Spedding; John A Peters; Anthony J Harmar
Journal:  Br J Pharmacol       Date:  2013-12       Impact factor: 8.739

8.  Asymmetric synthesis of conformationally constrained fingolimod analogues--discovery of an orally active sphingosine 1-phosphate receptor type-1 agonist and receptor type-3 antagonist.

Authors:  Ran Zhu; Ashley H Snyder; Yugesh Kharel; Lisa Schaffter; Qin Sun; Perry C Kennedy; Kevin R Lynch; Timothy L Macdonald
Journal:  J Med Chem       Date:  2007-11-10       Impact factor: 7.446

9.  Sphingosine-1-phosphate evokes unique segment-specific vasoconstriction of the renal microvasculature.

Authors:  Zhengrong Guan; Sean T Singletary; Anthony K Cook; Janet L Hobbs; Jennifer S Pollock; Edward W Inscho
Journal:  J Am Soc Nephrol       Date:  2014-02-27       Impact factor: 10.121

10.  FTY720 story. Its discovery and the following accelerated development of sphingosine 1-phosphate receptor agonists as immunomodulators based on reverse pharmacology.

Authors:  Kunitomo Adachi; Kenji Chiba
Journal:  Perspect Medicin Chem       Date:  2007-09-06
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