5-苯基-3-吡啶甲腈作为蛋白激酶Cθ抑制剂的优化
Optimization of 5-phenyl-3-pyridinecarbonitriles as PKCtheta inhibitors.
作者信息
Boschelli Diane H, Wang Daniel, Prashad Amar S, Subrath Joan, Wu Biqi, Niu Chuan, Lee Julie, Yang Xiaoke, Brennan Agnes, Chaudhary Divya
机构信息
Wyeth Research, Chemical Sciences, 401 N. Middletown Road, Pearl River, NY 10965, United States.
出版信息
Bioorg Med Chem Lett. 2009 Jul 1;19(13):3623-6. doi: 10.1016/j.bmcl.2009.04.126. Epub 2009 May 3.
The key intermediate, 4-chloro-5-iodo-3-pyridinecarbonitrile, allowed for ready optimization of the PKCtheta inhibitory activity of a series of 3-pyridinecarbonitriles. Analog 13b with a 4-methylindol-5-ylamino group at C-4 and a 4-(2-(4-methylpiperazin-1-yl)ethoxy)phenyl group at C-5 had an IC(50) value of 7.4nM for the inhibition of PKCtheta.
关键中间体4-氯-5-碘-3-吡啶甲腈使得一系列3-吡啶甲腈的蛋白激酶Cθ（PKCθ）抑制活性能够轻易得到优化。在C-4位带有4-甲基吲哚-5-基氨基且在C-5位带有4-(2-(4-甲基哌嗪-1-基)乙氧基)苯基的类似物13b对PKCθ抑制的IC(50)值为7.4 nM。
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