Ghotas Evindar; Sylvie G. Bernier; Malcolm J. Kavarana; Elisabeth Doyle; Jeanine Lorusso; Michael S. Kelley; Keith Halley; Amy Hutchings; Albion D. Wright; Ashis K. Sahaa; Gerhard Hannig; Barry A. Morgan; William F. Westlin
Bioorg. Med. Chem. Lett., 2009, 19, 2, 369-372
https://doi.org/10.1016/j.bmcl.2008.11.072

Abstract

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.