title: Fluoro analogs of bioactive oxy-sterols: Synthesis of an EBI2 agonist with enhanced metabolic stability.
abstract: Synthesis of several 7-hydroxy oxysterols and their potential roles as signaling molecules in the innate and adaptive immune responses is discussed. Discovery of a new, fluorinated, synthetic analog of the 7α,25-dihydroxycholesterol-the endogenous ligand of GPR 183 (EBI2), a G-protein coupled receptor highly expressed upon Epstein-Barr virus infection is described. Fluoro oxysterol 12 showed good metabolic stability while maintaining excellent EBI2 agonist activity.
authors.affiliation: Janssen Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Deng
authors.affiliation: Janssen Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors.forename: Siquan
authors.initials: S
authors.lastname: Sun
authors.affiliation: Janssen Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors.forename: Jiejun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Janssen Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors.forename: Chester
authors.initials: C
authors.lastname: Kuei
authors.affiliation: Janssen Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors.forename: Victory
authors.initials: V
authors.lastname: Joseph
authors.affiliation: Janssen Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors.forename: Changlu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Janssen Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, United States. Electronic address: nmani@its.jnj.com.
authors.forename: Neelakandha S
authors.initials: NS
authors.lastname: Mani
mesh_terms: D000818:Animals; D002460:Cell Line; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000072376:Oxysterols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: D000072376:Oxysterols; D043562:Receptors, G-Protein-Coupled
keywords: EBI2 agonist; Epstein–Barr virus; Fluoro oxysterol; GPR 183; Immune response; Oxysterols