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一系列4-吲哚基氨基-5-苯基-3-吡啶甲腈的合成及蛋白激酶Cθ抑制活性

Synthesis and PKCtheta inhibitory activity of a series of 4-indolylamino-5-phenyl-3-pyridinecarbonitriles.

作者信息

Dushin Russell G, Nittoli Thomas, Ingalls Charles, Boschelli Diane H, Cole Derek C, Wissner Allan, Lee Julie, Yang Xiaoke, Morgan Paul, Brennan Agnes, Chaudhary Divya

机构信息

Wyeth Research, Chemical Sciences, 401 N. Middletown Road, Pearl River, NY 10965, USA.

出版信息

Bioorg Med Chem Lett. 2009 May 1;19(9):2461-3. doi: 10.1016/j.bmcl.2009.03.053. Epub 2009 Mar 18.

DOI:10.1016/j.bmcl.2009.03.053
PMID:19345579
Abstract

A series of 4-indolylamino-5-phenyl-3-pyridinecarbonitrile inhibitors of PKCtheta were synthesized as potential anti-inflammatory agents. The effects of specific substitution on the 5-phenyl moiety and variations of the positional isomers of the 4-indolylamino substituent were explored. This study led to the discovery of compound 12d, which had an IC(50) value of 18nM for the inhibition of PKCtheta.

摘要

合成了一系列4-吲哚基氨基-5-苯基-3-吡啶甲腈类蛋白激酶Cθ（PKCθ）抑制剂，作为潜在的抗炎药。研究了5-苯基部分的特定取代以及4-吲哚基氨基取代基位置异构体变化的影响。该研究发现了化合物12d，其对PKCθ抑制作用的半数抑制浓度（IC50）值为18nM。

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