Design, synthesis, and in vitro bioactivity evaluation of fluorine-containing analogues for sphingosine-1-phosphate 2 receptor

Bioorg Med Chem. 2019 Aug 15;27(16):3619-3631. doi: 10.1016/j.bmc.2019.06.047. Epub 2019 Jun 29.

Abstract

Twenty eight new aryloxybenzene analogues were synthesized and their in vitro binding potencies toward S1PR2 were determined using a [32P]S1P competitive binding assay. Out of these new analogues, three compounds, 28c (IC50 = 29.9 ± 3.9 nM), 28e (IC50 = 14.6 ± 1.5 nM), and 28g (IC50 = 38.5 ± 6.3 nM) exhibited high binding potency toward S1PR2 and high selectivity over the other four receptor subtypes (S1PR1, 3, 4, and 5; IC50 > 1000 nM). Each of the three potent compounds 28c, 28e, and 28g contains a fluorine atom that will allow to develop F-18 labeled PET radiotracers for imaging S1PR2.

Keywords: Binding potency; Positron emission tomography; Selectivity; Sphingosine 1-phosphate receptor 2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fluorine / chemistry*
  • Humans
  • Sphingosine-1-Phosphate Receptors / chemistry*

Substances

  • Sphingosine-1-Phosphate Receptors
  • Fluorine