Stereochemistry–activity relationship of orally active tetralin S1P agonist prodrugs

…, WC Lee, D Scott, G Kumaravel, TL Macdonald…

Index: Ma, Bin; Guckian, Kevin M.; Lin, Edward Yin-Shiang; Lee, Wen-Cherng; Scott, Daniel; Kumaravel, Gnanasambandam; Macdonald, Timothy L.; Lynch, Kevin R.; Black, Cheryl; Chollate, Sowmya; Hahm, Kyungmin; Hetu, Gregg; Jin, Ping; Luo, Yi; Rohde, Ellen; Rossomando, Anthony; Scannevin, Robert; Wang, Joy; Yang, Chunhua Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 7 p. 2264 - 2269

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Citation Number: 7

Abstract

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.