Fluoro analogs of bioactive oxy-sterols: Synthesis of an EBI2 agonist with enhanced metabolic stability

Xiaohu Deng; Siquan Sun; Jiejun Wu; Chester Kuei; Victory Joseph; Changlu Liu; Neelakandha S Mani

doi:10.1016/j.bmcl.2016.09.029

Fluoro analogs of bioactive oxy-sterols: Synthesis of an EBI2 agonist with enhanced metabolic stability

Bioorg Med Chem Lett. 2016 Oct 15;26(20):4888-4891. doi: 10.1016/j.bmcl.2016.09.029. Epub 2016 Sep 12.

Authors

Xiaohu Deng¹, Siquan Sun¹, Jiejun Wu¹, Chester Kuei¹, Victory Joseph¹, Changlu Liu¹, Neelakandha S Mani²

Affiliations

¹ Janssen Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, United States.
² Janssen Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, United States. Electronic address: nmani@its.jnj.com.

PMID: 27658369
DOI: 10.1016/j.bmcl.2016.09.029

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.

Keywords: EBI2 agonist; Epstein–Barr virus; Fluoro oxysterol; GPR 183; Immune response; Oxysterols.

MeSH terms

Animals
Cell Line
Herpesvirus 4, Human / drug effects
Herpesvirus 4, Human / metabolism
Humans
Oxysterols / chemical synthesis
Oxysterols / chemistry*
Oxysterols / pharmacology
Receptors, G-Protein-Coupled / metabolism

Substances

Oxysterols
Receptors, G-Protein-Coupled