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

被引：135

作者：

Albert, R ^{[1
]}

Hinterding, K ^{[1
]}

Brinkmann, V ^{[1
]}

Guerini, D ^{[1
]}

Müller-Hartwieg, C ^{[1
]}

Knecht, H ^{[1
]}

Simeon, C ^{[1
]}

Streiff, M ^{[1
]}

Wagner, T ^{[1
]}

Welzenbach, K ^{[1
]}

Zécri, F ^{[1
]}

Zollinger, M ^{[1
]}

Cooke, N ^{[1
]}

Francotte, E ^{[1
]}

机构：

[1] Novartis Inst Biomed Res, CH-4056 Basel, Switzerland

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 16期

关键词：

D O I：

10.1021/jm050242f

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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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页码：5373 / 5377

页数：5

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