Ghotas Evindar; Alexander L. Satz; Sylvie G. Bernier; Malcolm J. Kavarana; Elisabeth Doyle; Jeanine Lorusso; Nazbeh Taghizadeh; Keith Halley; Amy Hutchings; Michael S. Kelley; Albion D. Wright; Ashis K. Saha; Gerhard Hannig; Barry A. Morgan; William F. Westlin
Bioorg. Med. Chem. Lett., 2009, 19, 8, 2315-2319
https://doi.org/10.1016/j.bmcl.2009.02.073

Abstract

In pursuit of potent and selective sphingosine-1-phosphate receptor agonists, we have utilized previously reported phenylamide and phenylimidazole scaffolds to explore extensive side-chain modifications to generate new molecular entities. A number of designed molecules demonstrate good selectivity and excellent in vitro and in vivo potency in both mouse and rat models. Oral administration of the lead molecule 11c (PPI-4667) demonstrated potent and dose-responsive lymphopenia.