• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>RSC Advances >SAR study on N-2, N-4-disubstituted pyrimidine-2,4-diamines as effective CDK2/CDK9 inhibitors and antiproliferative agents
【24h】

SAR study on N-2, N-4-disubstituted pyrimidine-2,4-diamines as effective CDK2/CDK9 inhibitors and antiproliferative agents

机译：SAR研究N-2，N-4-二取代的嘧啶-2,4-二胺作为有效的CDK2 / CDK9抑制剂和抗增殖剂

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Cyclin-dependent kinases (CDKs) are pivotal kinases in cell cycle transition and gene transcription. A series of N-2, N-4-diphenylpyrimidine-2,4-diamines were previously identified as potent CDK2/CDK9 inhibitors. To explore the SAR of this structural prototype, twenty-four novel N-2, N-4-disubstituted pyrimidine-2,4-diamines were designed and synthesized. Among them, twenty-one compounds exhibited potent inhibitory activities against both CDK2/cyclin A and CDK9/cyclin T1 systems, and the most potent CDK2 and CDK9 inhibitors, 3g and 3c, showed IC50 values of 83 nM and 65 nM respectively. Most of these compounds displayed significant inhibition against the tested tumor cell lines in the SRB assay, and in particular, remained active against the triple-negative breast cancer (TNBC) cell line MDA-MB-231. Flow cytometer analysis of compounds 2a, 2d and 3b in MDA-MB-231 cells indicated that these compounds induced cell cycle arrest in G2/M phase. Docking studies on compound 3g were performed, which provided conducive clues for further molecular optimization.
机译：细胞周期蛋白依赖性激酶（CDK）是细胞周期转换和基因转录中的枢轴激酶。先前，一系列N-2，N-4-二苯基嘧啶-2,4-二胺被鉴定为有效的CDK2 / CDK9抑制剂。为了探索该结构原型的SAR，设计并合成了二十四种新的N-2，N-4-二取代的嘧啶-2,4-二胺。其中，二十一种化合物对CDK2 / Cyclin A和CDK9 / Cyclin T1系统以及最有效的CDK2和CDK9抑制剂，3G和3C分别显示出83nm和65nm的IC 50值。大多数这些化合物对SRB测定中的测试肿瘤细胞系显示出显着的抑制，特别是对三阴性乳腺癌（TNBC）细胞系MDA-MB-231保持有效。 MDA-MB-231细胞中化合物2a，2d和3b的流式细胞仪分析表明，这些化合物在G2 / m相中诱导细胞周期停滞。进行了对化合物3G的对接研究，为进一步分子优化提供了有用的线索。

著录项

  • 来源
    《RSC Advances》 |2018年第22期|共15页
  • 作者

    Jing Liandong; Tang Yanbo; Goto Masuo; Lee Kuo-Hsiung; Xiao Zhiyan;

  • 作者单位

    Chinese Acad Med Sci Inst Mat Med Peking Union Med Coll Beijing Key Lab Act Subst Discovery &

    Druggabil E Beijing 100050 Peoples R China;

    Chinese Acad Med Sci Inst Mat Med Peking Union Med Coll Beijing Key Lab Act Subst Discovery &

    Druggabil E Beijing 100050 Peoples R China;

    Univ N Carolina UNC Eshelman Sch Pharm Nat Prod Res Labs Chapel Hill NC 27599 USA;

    Univ N Carolina UNC Eshelman Sch Pharm Nat Prod Res Labs Chapel Hill NC 27599 USA;

    Chinese Acad Med Sci Inst Mat Med Peking Union Med Coll Beijing Key Lab Act Subst Discovery &

    Druggabil E Beijing 100050 Peoples R China;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号