Discovery of 7-(3-(piperazin-1-yl)phenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives as highly potent and selective PI3Kδ inhibitors
Discovery of 7-(3-(piperazin-1-yl)phenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives as highly potent and selective PI3Kδ inhibitors
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DOI：
10.1016/j.bmcl.2017.01.016
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发表时间：
2017-02-15
影响因子：
2.7
通讯作者：
Poss, Michael A.
中科院分区：
文献类型：
--
作者：
Qin, Lan-Ying;Ruan, Zheming;Poss, Michael A.
如临床前动物模型所示，PI3K δ表达或其活性的破坏导致炎症和免疫反应的减少。因此，抑制PI3K δ可能为自身免疫性疾病，如RA、SLE和呼吸系统疾病提供一种替代治疗方法。在此，我们发现7-（3-（哌嗪-1-基）苯基）吡咯[2,1-f[1,2,4]三嗪-4-胺衍生物是高效、选择性和口服生物可利用的PI3K δ抑制剂。先导化合物在小鼠体内KLH模型中显示出有效性。(C) 2017 Elsevier Ltd.版权所有。
As demonstrated in preclinical animal models, the disruption of PI3K delta expression or its activity leads to a decrease in inflammatory and immune responses. Therefore, inhibition of PI3K delta may provide an alternative treatment for autoimmune diseases, such as RA, SLE, and respiratory ailments. Herein, we disclose the identification of 7-(3-(piperazin-1-yl)phenyl)pyrrolo[2,1-f[1,2,4]triazin-4-amine derivatives as highly potent, selective and orally bioavailable PI3K delta inhibitors. The lead compound demonstrated efficacy in an in vivo mouse KLH model. (C) 2017 Elsevier Ltd. All rights reserved.