@article{b47cab0715e143ecb3c85c8fc1e9a235,
title = "Design and synthesis of pyrazolopyridine derivatives as sphingosine 1-phosphate receptor 2 ligands",
abstract = "Eleven new sphingosine 1-phosphate receptor 2 (S1PR2) ligands were synthesized by modifying lead compound N-(2,6-dichloropyridin-4-yl)-2-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)hydrazine-1-carboxamide (JTE-013) and their binding affinities toward S1PRs were determined in vitro using [32P]S1P and cell membranes expressing recombinant human S1PRs. Among these ligands, 35a (IC50 = 29.1 ± 2.6 nM) and 35b (IC50 = 56.5 ± 4.0 nM) exhibit binding potency toward S1PR2 comparable to JTE-013 (IC50 = 58.4 ± 7.4 nM) with good selectivity for S1PR2 over the other S1PRs (IC50 > 1000 nM). Further optimization of these analogues may identify additional and more potent and selective compounds targeting S1PR2.",
keywords = "Binding affinities, Multiple sclerosis, Selectivity, Sphingosine 1-phosphate receptor 2",
author = "Zonghua Luo and Xuyi Yue and Hao Yang and Hui Liu and Klein, {Robyn S.} and Zhude Tu",
note = "Funding Information: This study was supported by the National Multiple Sclerosis Society [ RG150705331 ] and USA Department of Energy (DOE) Training Grants [ DESC0008432 and DESC0012737 ]. It was partially supported by USA National Institutes of Health (NIH) through the National Institute of Neurological Disorders and Stroke [ NS075527 ] and the National Institute of Mental Health [ MH092797 ]. Mass spectrometry was generated from the Washington University Mass Spectrometry facility that is supported by NIH . Funding Information: This study was supported by the National Multiple Sclerosis Society [RG150705331] and USA Department of Energy (DOE) Training Grants [DESC0008432 and DESC0012737]. It was partially supported by USA National Institutes of Health (NIH) through the National Institute of Neurological Disorders and Stroke [NS075527] and the National Institute of Mental Health [MH092797]. Mass spectrometry was generated from the Washington University Mass Spectrometry facility that is supported by NIH. Publisher Copyright: {\textcopyright} 2017 Elsevier Ltd",
year = "2018",
month = feb,
day = "1",
doi = "10.1016/j.bmcl.2017.12.010",
language = "English",
volume = "28",
pages = "488--496",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
number = "3",
}