Design, synthesis, and in vitro bioactivity evaluation of fluorine-containing analogues for sphingosine-1-phosphate 2 receptor. Issue 16 (15th August 2019)

• Record Type: Journal Article
• Authors: Luo, Zonghua; Liu, Hui; Klein, Robyn S.; Tu, Zhude
• Is Part Of: Bioorganic & medicinal chemistry. Volume 27:Issue 16(2019)
• Page Start: 3619
• Page End: 3631
• Publication Date: 2019-08-15
• Subjects: S1P sphingosine 1-phosphate -- S1PR sphingosine 1-phosphate receptor -- CNS central nervous system -- EAC esophageal adenocarcinoma -- EAE experimental autoimmune encephalomyelitis -- MS multiple sclerosis -- BBB blood-brain barrier -- PET positron emission tomography -- DMF N, N-dimethylformamide -- DMA N, N-dimethylacetamide -- DIPEA N, N-diisopropylethylamine -- DMSO dimethyl sulfoxide -- THF tetrahydrofuran -- RT room temperature -- TLC thin-layer chromatography; Sphingosine 1-phosphate receptor 2 -- Binding potency -- Selectivity -- Positron emission tomography; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2019.06.047
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: 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 (IC50 = 29.9 ± 3.9 nM), 28e (IC50 = 14.6 ± 1.5 nM), and28g (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 compounds28c, 28e, and28g contains a fluorine atom that will allow to develop F-18 labeled PET radiotracers for imaging S1PR2.