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

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.

SUBMITTER: Luo Z

PROVIDER: S-EPMC6698139 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Luo Zonghua Z Liu Hui H Klein Robyn S RS Tu Zhude Z

Bioorganic & medicinal chemistry 20190629 16

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). Eac ...[more]

PMID: 31279524

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