4区 · 医学
Article
作者: Evindar, Ghotas ; Wright, Albion D. ; Saha, Ashis K. ; Halley, Keith ; Doyle, Elisabeth ; Lorusso, Jeanine ; Hutchings, Amy ; Morgan, Barry A. ; Bernier, Sylvie G. ; Hannig, Gerhard ; Kavarana, Malcolm J. ; Kelley, Michael S. ; Westlin, William F.
In the design of potent and selective sphingosine-1-phosphate receptor agonists, we were able to identify two series of molecules based on phenylamide and phenylimidazole analogs of FTY-720. Several designed molecules in these scaffolds have demonstrated selectivity for S1P receptor subtype 1 versus 3 and excellent in vivo activity in mouse. Two molecules PPI-4621 (4b) and PPI-4691 (10a), demonstrated dose responsive lymphopenia, when administered orally.