Optimization of 5-vinylaryl-3-pyridinecarbonitriles as PKCθ inhibitors

被引：19

作者：

Boschelli, Diane H. ^{[1
]}

Subrath, Joan ^{[1
]}

Niu, Chuansheng ^{[1
]}

Wu, Biqi ^{[1
]}

Wang, Yan ^{[1
]}

Lee, Julie ^{[2
]}

Brennan, Agnes ^{[2
]}

Ho, Melisa ^{[2
]}

Deng, Bijia ^{[2
]}

Yang, Xiaoke ^{[2
]}

Xu, Xin ^{[3
]}

Leung, Louis ^{[4
]}

Wang, Jianyao ^{[4
]}

Atherton, James ^{[4
]}

Chaudhary, Divya ^{[2
]}

机构：

[1] Wyeth Res, Pearl River, NY 10965 USA

[2] Wyeth Res, Inflammat, Cambridge, MA 02140 USA

[3] Wyeth Res, Drug Safety & Metab, Andover, MA 01810 USA

[4] Wyeth Res, Drug Safety & Metab, Collegeville, PA 19426 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 06期

关键词：

Kinase; PKC theta; 3-Pyridinecarbonitrile; PROTEIN-KINASE-C; SYSTEMIC-LUPUS-ERYTHEMATOSUS; VINYLBORONATE ESTER; ARYL HALIDES; AEB071; DELTA; MICE;

D O I：

10.1016/j.bmcl.2010.01.119

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Analog 8, a 3-pyridinecarbonitrile with an (E)-2-{6-[(4-methylpiperazin-1-yl) methyl]pyridin-2-yl} vinyl group at C-5, had an IC(50) value of 1.1 nM for the inhibition of PKC theta and potently blocked the production of IL-2 in both stimulated murine T cells (IC(50) = 34 nM) and human whole blood (IC(50) = 500 nM). (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：1965 / 1968

页数：4

共 21 条

[21] Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a Potent and Selective Inhibitor of Protein Kinase C Isotypes [J].

Wagner, Juergen ;

von Matt, Peter ;

Sedrani, Richard ;

Albert, Rainer ;

Cooke, Nigel ;

Ehrhardt, Claus ;

Geiser, Martin ;

Rummel, G'abriele ;

Stark, Wilhelm ;

Strauss, Andre ;

Cowan-Jacob, Sandra W. ;

Beerli, Christian ;

Weckbecker, Gisbert ;

Evenou, Jean-Pierre ;

Zenke, Gerhard ;

Cottens, Sylvain .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (20) :6193-6196

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