title: Stereochemistry-activity relationship of orally active tetralin S1P agonist prodrugs.
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.
authors.affiliation: BiogenIdec Inc., 14 Cambridge Center, Cambridge, MA 02142, USA. bin.ma@biogenidec.com
authors.forename: Bin
authors.initials: B
authors.lastname: Ma
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Guckian
authors.forename: Edward Yin-Shiang
authors.initials: EY
authors.lastname: Lin
authors.forename: Wen-Cherng
authors.initials: WC
authors.lastname: Lee
authors.forename: Daniel
authors.initials: D
authors.lastname: Scott
authors.forename: Gnanasambandam
authors.initials: G
authors.lastname: Kumaravel
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Macdonald
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Lynch
authors.forename: Cheryl
authors.initials: C
authors.lastname: Black
authors.forename: Sowmya
authors.initials: S
authors.lastname: Chollate
authors.forename: Kyungmin
authors.initials: K
authors.lastname: Hahm
authors.forename: Gregg
authors.initials: G
authors.lastname: Hetu
authors.forename: Ping
authors.initials: P
authors.lastname: Jin
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.forename: Ellen
authors.initials: E
authors.lastname: Rohde
authors.forename: Anthony
authors.initials: A
authors.lastname: Rossomando
authors.forename: Robert
authors.initials: R
authors.lastname: Scannevin
authors.forename: Joy
authors.initials: J
authors.lastname: Wang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018360:Crystallography, X-Ray; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D008231:Lymphopenia / Q000139:chemically induced; D051379:Mice; D008958:Models, Molecular; D009103:Multiple Sclerosis / Q000188:drug therapy; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D049349:Receptors, Lysosphingolipid / Q000819:agonists* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D000099157:Sphingosine Kinase
chemical_list: D007166:Immunosuppressive Agents; D017853:Phosphotransferases (Alcohol Group Acceptor); D011355:Prodrugs; D049349:Receptors, Lysosphingolipid; D013764:Tetrahydronaphthalenes; D000099157:Sphingosine Kinase; C095210:tetralin