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

Stephen Shane Scully; Alicia J Tang; Morten Lundh; Carrie M Mosher; Kedar M Perkins; Bridget K Wagner

doi:10.1021/jm400397x

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

Stephen Shane Scully, Alicia J Tang, Morten Lundh, Carrie M Mosher, Kedar M Perkins, Bridget K Wagner

Endocrinology and Metabolism

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

24 Citationer (Scopus)

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-¿.

Originalsprog	Engelsk
Tidsskrift	Journal of Medicinal Chemistry
Vol/bind	56
Udgave nummer	10
Sider (fra-til)	4125-4129
Antal sider	6
ISSN	0022-2623
DOI	https://doi.org/10.1021/jm400397x
Status	Udgivet - 25 apr. 2013

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Citationsformater

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AU - Scully, Stephen Shane

AU - Tang, Alicia J

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AU - Mosher, Carrie M

AU - Perkins, Kedar M

AU - Wagner, Bridget K

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AB - 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-¿.

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