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Small-Molecule Inhibitors of Cytokine-Mediated STAT1 Signal Transduction In ß-Cells With Improved Aqueous Solubility

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Authors:
  • Scully, Stephen Shane ;
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    unknown
  • Tang, Alicia J ;
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    unknown
  • Lundh, Morten ;
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    Endocrinology and Metabolism, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
  • Mosher, Carrie M ;
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  • Perkins, Kedar M ;
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  • Wagner, Bridget K
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DOI:
10.1021/jm400397x
Abstract:
We previously reported the discovery of BRD0476 (1), a small molecule generated by diversity-oriented synthesis that suppresses cytokine-induced ß-cell apoptosis. Herein, we report the synthesis and biological evaluation of 1 and analogs with improved aqueous solubility. By replacing naphthyl with quinoline moieties, we prepared active analogs with up to a 1400-fold increase in solubility from 1. In addition, we demonstrated that compound 1 and analogs inhibit STAT1 signal transduction induced by IFN-¿.
Type:
Journal article
Language:
English
Published in:
Journal of Medicinal Chemistry, 2013, Vol 56, Issue 10, p. 4125-4129
Main Research Area:
Medical science
Publication Status:
Published
Review type:
Peer Review
Submission year:
2013
Scientific Level:
Scientific
ID:
241859814

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