title: Synthesis and evaluation of alkoxy-phenylamides and alkoxy-phenylimidazoles as potent sphingosine-1-phosphate receptor subtype-1 agonists.
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.
authors.affiliation: Department of Medicinal Chemistry, Praecis Pharmaceuticals Incorporated, 830 Winter Street, Waltham, MA 02451, USA. ghotas.x.evindar@gsk.com
authors.forename: Ghotas
authors.initials: G
authors.lastname: Evindar
authors.forename: Sylvie G
authors.initials: SG
authors.lastname: Bernier
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Kavarana
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Doyle
authors.forename: Jeanine
authors.initials: J
authors.lastname: Lorusso
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kelley
authors.forename: Keith
authors.initials: K
authors.lastname: Halley
authors.forename: Amy
authors.initials: A
authors.lastname: Hutchings
authors.forename: Albion D
authors.initials: AD
authors.lastname: Wright
authors.forename: Ashis K
authors.initials: AK
authors.lastname: Saha
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hannig
authors.forename: Barry A
authors.initials: BA
authors.lastname: Morgan
authors.forename: William F
authors.initials: WF
authors.lastname: Westlin
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D049349:Receptors, Lysosphingolipid / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D007093:Imidazoles; D049349:Receptors, Lysosphingolipid