title: Synthesis, identification, and biological activity of metabolites of two novel selective S1P1 agonists.
abstract: SYL927 and SYL930 are selective S1P1 agonists under preclinical development. However, during their pharmacokinetic studies we detected two metabolites in rat blood that were tentatively identified as monohydroxylated metabolites of SYL927 and SYL930 based on LC-MS/MS data. In this study, we designed and synthesized possible monohydroxylated products 6a-e and used them as references to confirm the structures of the two metabolites detected by LC-MS/MS. We also evaluated the in vitro and in vivo biological activities of these two metabolites.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China; Department of Medicinal Chemistry, Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica & Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China; Department of Medicinal Chemistry, Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica & Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China; Department of Medicinal Chemistry, Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica & Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China.
authors.forename: Meiyang
authors.initials: M
authors.lastname: Xi
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China; Department of Medicinal Chemistry, Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica & Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China; Department of Medicinal Chemistry, Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica & Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China. Electronic address: yindali@imm.ac.cn.
authors.forename: Dali
authors.initials: D
authors.lastname: Yin
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D000068876:Fingolimod Hydrochloride / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006900:Hydroxylation; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D049349:Receptors, Lysosphingolipid / Q000819:agonists* / Q000276:immunology; D053719:Tandem Mass Spectrometry
chemical_list: D007166:Immunosuppressive Agents; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride
keywords: Metabolites; Monohydroxylated products; S1P(1)