title: Exploring amino acids derivatives as potent, selective, and direct agonists of sphingosine-1-phosphate receptor subtype-1.
abstract: In the quest to discover a potent and selective class of direct agonists to the sphingosine-1-phosphate receptor, we explored the carboxylate functional group as a replacement to previously reported lead phosphates. This has led to the discovery of potent and selective direct agonists with moderate to substantial in vivo lymphopenia. The previously reported selectivity enhancing moiety (SEM) and selectivity enhancing orientation (SEO) in the phenylamide and phenylimidazole scaffolds were crucial to obtaining selectivity for S1P receptor subtype 1 over 3.
authors.affiliation: Department of Medicinal Chemistry, Praecis Pharmaceuticals Incorporated (Currently GlaxoSmithKline), 830 Winter Street, Waltham, MA 02451, USA. ghotas.x.evindar@gsk.com
authors.forename: Ghotas
authors.initials: G
authors.lastname: Evindar
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Deng
authors.forename: Sylvie G
authors.initials: SG
authors.lastname: Bernier
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Doyle
authors.forename: Jeanine
authors.initials: J
authors.lastname: Lorusso
authors.forename: Barry A
authors.initials: BA
authors.lastname: Morgan
authors.forename: William F
authors.initials: WF
authors.lastname: Westlin
mesh_terms: D000284:Administration, Oral; D000596:Amino Acids / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D020128:Inhibitory Concentration 50; D008231:Lymphopenia; D051379:Mice; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D049349:Receptors, Lysosphingolipid / Q000819:agonists* / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000596:Amino Acids; D049349:Receptors, Lysosphingolipid