Stereochemistry-activity relationship of orally active tetralin S1P agonist prodrugs

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:20

Article

Ma, Bin¹  Guckian, Kevin M.¹  Lin, Edward Yin-Shiang¹  Lee, Wen-Cherng¹  Scott, Daniel¹  Kumaravel, Gnanasambandam¹  Macdonald, Timothy L.²  Lynch, Kevin R.^3,4  Black, Cheryl¹  Chollate, Sowmya¹  Hahm, Kyungmin¹  Hetu, Gregg¹  Jin, Ping¹  Luo, Yi¹  Rohde, Ellen¹  Rossomando, Anthony¹  Scannevin, Robert¹  Wang, Joy¹  Yang, Chunhua¹ 

[1] Biogenldec Inc, Cambridge, MA 02142 USA

[2] Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA

[3] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22904 USA

[4] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22904 USA

关键词: S1P;    FTY720;    Multiple sclerosis;    SphK2;    Prodrug;    Tetralin;    X-ray;   

DOI  :  10.1016/j.bmcl.2010.02.006

来源: Elsevier

【 摘 要 】

Modifying FTY720, an immunosuppressant modulator, led to a new series of well phosphorylated tetralin analogs as potent S1P1 receptor agonists. The stereochemistry effect of tetralin ring was probed, and (-)(R)-2-amino-2-((S)-6-octyl-1,2,3,4-tetrahydronaphthalen-2-yl)propan-1-ol was identified as a good SphK2 substrate and potent S1P1 agonist with good oral bioavailability. (C) 2010 Elsevier Ltd. All rights reserved.

【 授权许可】

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