Novel potent and selective calcium-release-activated calcium (CRAC) channel inhibitors. Part 2: Synthesis and inhibitory activity of aryl-3-trifluoromethylpyrazoles

Bioorganic & Medicinal Chemistry
Yasuhiro YonetokuShin-ichi Tsukamoto

Abstract

To identify potent and selective calcium-release-activated calcium (CRAC) channel inhibitors, we examined the structure-activity relationships of the pyrazole and thiophene moieties in compound 4. Compound 25b was found to exhibit highly potent and selective inhibitory activity for CRAC channels and further modifications of the pyrazole and benzoyl moieties of compound 25b produced compound 29. These compounds were potent inhibitors of IL-2 production in vitro and also acted as inhibitors in pharmacological models of diseases resulting from T-lymphocyte activation, after oral administration.

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Citations

Mar 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·Shigeki KiyonakaYasuo Mori
Dec 20, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chun LiJuan Xie
Sep 22, 2012·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Stefan FrischbutterRia Baumgrass
Mar 20, 2008·Expert Opinion on Therapeutic Targets·Yina H HuangKarsten Sauer
May 5, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Hassan M FaidallahKhalid A Khan
Jul 4, 2015·Organic & Biomolecular Chemistry·Thang Ngoc NgoPeter Langer
Mar 31, 2009·ChemMedChem·Zachary K SweeneySilvia Patrick
Feb 19, 2019·SAR and QSAR in Environmental Research·S Bhuvaneshwari, K Sankaranarayanan
Mar 12, 2013·The Journal of Pharmacology and Experimental Therapeutics·Fen-Fen LinHelen J McBride
Dec 17, 2011·The Journal of Organic Chemistry·Igor I GerusPavel K Mykhailiuk
Jul 5, 2011·The Journal of Organic Chemistry·David ObermayerC Oliver Kappe
Jan 26, 2010·Bioorganic & Medicinal Chemistry Letters·Akinobu Z SuzukiKatsuhiko Mikoshiba

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