Twenty eight new aryloxybenzene analogues were synthesized and their in vitro binding potencies toward S1PR2 were determined using a [ 32 P]S1P competitive binding assay. Out of these new analogues, three compounds, 28c (IC 50 = 29.9 ± 3.9 nM), 28e (IC 50 = 14.6 ± 1.5 nM), and 28g (IC 50 = 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; IC 50 > 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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)