Small-molecule inhibitors of cytokine-mediated STAT1 signal transduction in β-cells with improved aqueous solubility.

J Med Chem
Authors
Keywords
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.

Year of Publication
2013
Journal
J Med Chem
Volume
56
Issue
10
Pages
4125-9
Date Published
2013 May 23
ISSN
1520-4804
DOI
10.1021/jm400397x
PubMed ID
23617753
PubMed Central ID
PMC3690275
Links
Grant list
DP2 DK083048 / DK / NIDDK NIH HHS / United States
Howard Hughes Medical Institute / United States