Syntheses and in vitro evaluation of new S1PR1 compounds and initial evaluation of a lead F-18 radiotracer in rodents.

ABSTRACT: Thirteen new sphingosine-1-phosphate receptor 1 (S1PR1) ligands were designed and synthesized by replacing azetidine-3-carboxylic acid moiety of compound 4 with new polar groups. The in vitro binding potency of these new analogs toward S1PR1 was determined. Out of 13 new compounds, four compounds 9a, 10c, 12b, and 16b displayed high S1PR1 binding potency with IC₅₀ values of 13.2 ± 3.2, 14.7 ± 1.7, 9.7 ± 1.6, and 6.3 ± 1.3 nM, respectively; further binding studies of these four ligands toward S1PR2-5 suggested they are highly selective for S1PR1 over other S1PRs. The radiosynthesis of the lead radiotracer [¹⁸F]12b was achieved with good radiochemical yield (∼14.1%), high radiochemical purity (>98%), and good specific activity (∼54.1 GBq/μmol, decay corrected to the end

SUBMITTER: Luo Z 

PROVIDER: S-EPMC5908474 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature