Potent S1P receptor agonists replicate the pharmacologic actions of the novel immune modulator FTY720

  • Bioorg Med Chem Lett. 2004 Jun 21;14(12):3351-5. doi: 10.1016/j.bmcl.2004.02.106.
Jeffrey J Hale  1 ,  William Neway ,  Sander G Mills ,  Richard Hajdu ,  Carol Ann Keohane ,  Mark Rosenbach ,  James Milligan ,  Gan-Ju Shei ,  Gary Chrebet ,  James Bergstrom ,  Deborah Card ,  Gloria C Koo ,  Sam L Koprak ,  Jesse J Jackson ,  Hugh Rosen ,  Suzanne Mandala
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. [email protected]
PMID: 15149705 DOI: 10.1016/j.bmcl.2004.02.106
Abstract

Alteration in lymphocyte trafficking and prevention of graft rejection in rodents observed on exposure to FTY720 (1) or its corresponding phosphate ester 2 can be induced by the systemic administration of potent sphingosine-1-phosphate receptor agonists exemplified by 19. The similar S1P receptor profiles of 2 and 19 coupled with their comparable potency in vivo supports a connection between S1P receptor agonism and immunosuppressive efficacy.