S1P receptor mediated activity of FTY720 phosphate mimics.
Various carboxylic acids, phosphonic acids, sulfonic acids, tetrazoles as well as sulfonylhydantoins were prepared as phosphate mimics of the chiral aminophosphate 1-P to act as agonists on the S1P(1) receptor. It was found that amino phosphonates and amino carboxylates are potent S1P(1) binders. beta-Amino acid 11 could be shown to reversibly reduce blood lymphocyte counts in rats after po administration.
Novartis Institutes for BioMedical Research, Novartis Campus, CH-4056 Basel, Switzerland. klemens.hoegenauer@novartis.com
Klemens
K
Högenauer
Klaus
K
Hinterding
Peter
P
Nussbaumer
D000284:Administration, Oral; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007532:Isoleucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D010710:Phosphates / Q000737:chemistry*; D010766:Phosphorylation; D011409:Propylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D049349:Receptors, Lysosphingolipid / Q000819:agonists* / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D000596:Amino Acids; D007166:Immunosuppressive Agents; D010710:Phosphates; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D007532:Isoleucine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine