Synthesis and biological properties of novel sphingosine derivatives.
Sphingosine-1-phosphate (S-1P) derivatives such as threo-(2S,3S)-analogues, which are C-3 stereoisomers of natural erythro-(2S,3R)-S-1P, have been synthesized starting from l-serine or (1S,2S)-2-amino-1-aryl-1,3-propanediols (6). threo-(1S,2R)-2-Amino-1-aryl-3-bromopropanols (HBr salt) have also been prepared from 6. The threo-S-1Ps and the threo-amino-bromide derivatives have shown potent inhibitory activity against Ca(2+) ion mobilization in HL60 cells induced by erythro-S-1P, suggesting that these compounds would compete with cell surface EDG/S1P receptors.
Murakami
Teiichi
T
National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 5, Tsukuba, Ibaraki 305-8565, Japan. t-murakami@aist.go.jp
Furusawa
Kiyotaka
K
Tamai
Tadakazu
T
Yoshikai
Kazuyoshi
K
Nishikawa
Masazumi
M
D020013:Calcium Signaling / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D008246:Lysophospholipids / Q000138:chemical synthesis* / Q000494:pharmacology; D049349:Receptors, Lysosphingolipid / Q000819:agonists / Q000037:antagonists & inhibitors; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C481931:erythro-(2R,3S)-sphingosine; C060506:sphingosine 1-phosphate; D013110:Sphingosine