title: Synthesis of new ligands for targeting the S1P1 receptor.
abstract: Sphingosine-1-phosphate (S1P) influences various fundamental biological processes by interacting with a family of five G protein-coupled receptors (S1P1-5). FTY720, a sphingosine analogue, which was approved for treatment of relapsing forms of multiple sclerosis, is phosphorylated in vivo and acts as an agonist of four of the five S1P receptor subtypes. Starting from these lead structures we developed new agonists for the S1P1 receptor. The biological activity was tested in vivo and promising ligands were fluorinated at different positions to identify candidates for positron emission tomography (PET) imaging after [(18)F]-labelling. The radioligands shall enable the imaging of S1P1 receptor expression in vivo and thus may serve as novel imaging markers of S1P-related diseases.
authors: Organic Chemistry Institute, University of Münster, Corrensstraße 40, D-48149 Münster, Germany.
authors: Stefanie S
authors: SS
authors: Schilson
authors: Institute for Pathophysiology, Westdeutsches Herz- und Gefäßzentrum, University Hospital, Essen, University of Duisburg-Essen, Hufelandstraße 55, D-45122 Essen, Germany.
authors: Petra
authors: P
authors: Keul
authors: Organic Chemistry Institute, University of Münster, Corrensstraße 40, D-48149 Münster, Germany; NRW Graduate School of Chemistry, University of Münster, Wilhelm-Klemm-Straße 10, D-48149 Münster, Germany.
authors: Rizwan S
authors: RS
authors: Shaikh
authors: Department of Nuclear Medicine, University of Münster, Albert-Schweizer-Campus 1, D-48149 Münster, Germany; European Institute for Molecular Imaging, University of Münster, Waldeyerstraße 15, D-48149 Münster, Germany; Cells-in-Motion, Centre of Excellence, University of Münster, Waldeyerstraße 15, D-48149 Münster, Germany.
authors: Michael
authors: M
authors: Schäfers
authors: Institute for Pathophysiology, Westdeutsches Herz- und Gefäßzentrum, University Hospital, Essen, University of Duisburg-Essen, Hufelandstraße 55, D-45122 Essen, Germany.
authors: Bodo
authors: B
authors: Levkau
authors: Organic Chemistry Institute, University of Münster, Corrensstraße 40, D-48149 Münster, Germany; European Institute for Molecular Imaging, University of Münster, Waldeyerstraße 15, D-48149 Münster, Germany; Cells-in-Motion, Centre of Excellence, University of Münster, Waldeyerstraße 15, D-48149 Münster, Germany. Electronic address: haufe@uni-muenster.de.
authors: Günter
authors: G
authors: Haufe
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000068876:Fingolimod Hydrochloride / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D049349:Receptors, Lysosphingolipid / Q000187:drug effects* / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D008024:Ligands; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride
keywords: FTY720 analogues; Fluorine; G protein-coupled receptors; S1P(1) receptor agonists; Sphingosine-1-phosphate (S1P); Structure–activity relationship