title: New fluorinated agonists for targeting the sphingosin-1-phosphate receptor 1 (S1P(1)).
abstract: The sphingosine-1-phosphate receptor type 1 (S1P1) is involved in fundamental biological processes such as regulation of immune cell trafficking, vascular barrier function and angiogenesis. This Letter presents multistep syntheses of various fluorine substituted 12-aryl analogues of the drug fingolimod (FTY720) and a seven-steps route to 2-amino-17,17-difluoro-2-(hydroxymethyl)heptadecan-1-ol. In vitro and in vivo tests proved all these compounds as potent S1P1 receptor agonists.
authors.affiliation: Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, D-48149 Münster, Germany; NRW Graduate School of Chemistry, Westfälische Wilhelms-Universität Münster, Wilhelm-Klemm-Straße 10, D-48149 Münster, Germany.
authors.forename: Rizwan S
authors.initials: RS
authors.lastname: Shaikh
authors.affiliation: Institute for Pathophysiology, Westdeutsches Herz- und Gefäßzentrum, University Hospital, Essen, University of Duisburg-Essen, Hufelandstraße 55, D-45122 Essen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Keul
authors.affiliation: Klinik für Nuklearmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude A1, D-48149 Münster, Germany; European Institute for Molecular Imaging-EIMI, Westfälische Wilhelms-Universität Münster, Waldeyerstraße 15, D-48149 Münster, Germany; Cells-in-Motion Centre of Excellence, Westfälische Wilhelms-Universität Münster, Waldeyerstraße 15, D-48149 Münster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
authors.affiliation: Institute for Pathophysiology, Westdeutsches Herz- und Gefäßzentrum, University Hospital, Essen, University of Duisburg-Essen, Hufelandstraße 55, D-45122 Essen, Germany.
authors.forename: Bodo
authors.initials: B
authors.lastname: Levkau
authors.affiliation: Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, D-48149 Münster, Germany; European Institute for Molecular Imaging-EIMI, Westfälische Wilhelms-Universität Münster, Waldeyerstraße 15, D-48149 Münster, Germany; Cells-in-Motion Centre of Excellence, Westfälische Wilhelms-Universität Münster, Waldeyerstraße 15, D-48149 Münster, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Haufe
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D016466:CHO Cells; D003412:Cricetulus; D005233:Fatty Alcohols / Q000138:chemical synthesis / Q000494:pharmacology*; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D049349:Receptors, Lysosphingolipid / Q000819:agonists*; D000081025:Sphingosine-1-Phosphate Receptors
chemical_list: C000609660:2-amino-17,17-difluoro-2-(hydroxymethyl)heptadecan-1-ol; D005233:Fatty Alcohols; D006845:Hydrocarbons, Fluorinated; D007166:Immunosuppressive Agents; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000068876:Fingolimod Hydrochloride
keywords: FTY720 analogues; Fluorine; G protein-coupled receptors; S1P(1) receptor agonist; Sphingosine-1-phosphate (S1P)