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Journal of medicinal chemistry DOI:10.1021/jm400397x

Small-Molecule Inhibitors of Cytokine-Mediated STAT1 Signal Transduction in β-Cells with Improved Aqueous Solubility.

Publication TypeJournal Article
Year of Publication2013
AuthorsScully, SS, Tang, AJ, Lundh, M, Mosher, CM, Perkins, KM, Wagner, BK
JournalJournal of medicinal chemistry
Volume56
Issue10
Pages4125-9
Date Published2013/05/23
ISSN0022-2623
Abstract

We previously reported the discovery of BRD0476 (1), a small molecule generated by diversity-oriented synthesis that suppresses cytokine-induced β-cell apoptosis. Herein, we report the synthesis and biological evaluation of 1 and analogues with improved aqueous solubility. By replacing naphthyl with quinoline moieties, we prepared active analogues with up to a 1400-fold increase in solubility from 1. In addition, we demonstrated that 1 and analogues inhibit STAT1 signal transduction induced by IFN-γ.

URLhttp://dx.doi.org/10.1021/jm400397x
DOI10.1021/jm400397x
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23617753?dopt=Abstract