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

ABSTRACT: We previously reported the discovery of BRD0476 (1), a small molecule generated by diversity-oriented synthesis that suppresses cytokine-induced ?-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-?.

SUBMITTER: Scully SS

PROVIDER: S-EPMC3690275 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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

Scully Stephen S SS Tang Alicia J AJ Lundh Morten M Mosher Carrie M CM Perkins Kedar M KM Wagner Bridget K BK

Journal of medicinal chemistry 20130513 10

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 I ...[more]

PMID: 23617753

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