2,4-difluoro-N-(2-methoxy-5-(4-(3-(4-(methylsulfonyl)piperazin-1-yl)prop-1-yn-1-yl)quinolin-6-yl)pyridin-3-yl)benzenesulfonamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2,4-difluoro-N-(2-methoxy-5-(4-(3-(4-(methylsulfonyl)piperazin-1-yl)prop-1-yn-1-yl)quinolin-6-yl)pyridin-3-yl)benzenesulfonamide
• 英文别名: 2,4-Difluoro-N-[2-methoxy-5-[4-[3-(4-methylsulfonylpiperazin-1-yl)prop-1-ynyl]quinolin-6-yl]pyridin-3-yl]benzenesulfonamide；2,4-difluoro-N-[2-methoxy-5-[4-[3-(4-methylsulfonylpiperazin-1-yl)prop-1-ynyl]quinolin-6-yl]pyridin-3-yl]benzenesulfonamide
• 化学式: C₂₉H₂₇F₂N₅O₅S₂
• 分子量: 627.693
• InChiKey: BBRINJUWZRLWKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  43
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  139
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  N-(5-溴-2-甲氧基吡啶-3-基)-2,4-二氟苯磺酰胺 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 palladium diacetate 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 联硼酸频那醇酯 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 2,4-difluoro-N-(2-methoxy-5-(4-(3-(4-(methylsulfonyl)piperazin-1-yl)prop-1-yn-1-yl)quinolin-6-yl)pyridin-3-yl)benzenesulfonamide
  参考文献：
  名称：

  发现苯磺酰胺衍生物作为有效的PI3K / mTOR双重抑制剂，具有体内抗肝细胞癌的功效

  摘要：

  磷酸肌醇3-激酶（PI3K）/蛋白激酶B（AKT）/雷帕霉素的哺乳动物靶标（mTOR）信号通路与细胞活性有关。在包括肝细胞癌（HCC）在内的各种癌症中发现了该信号通路的异常。提出PI3K / mTOR双重抑制剂通过靶向信号传导途径的多个点而具有增强的抗肿瘤功效。我们合成了一系列丙炔基取代的苯磺酰胺衍生物作为PI3K / mTOR双重抑制剂。化合物7k（NSC781406）被鉴定为高效双重抑制剂，在肝细胞癌BEL-7404异种移植模型中显示出有效的肿瘤生长抑制作用。化合物7k可能是HCC的潜在治疗药物候选物。

  DOI：

  10.1016/j.bmc.2016.01.008

文献信息

• Design, synthesis and biological evaluation of novel 4-alkynyl-quinoline derivatives as PI3K/mTOR dual inhibitors
  作者：Xiaoqing Lv、Huazhou Ying、Xiaodong Ma、Ni Qiu、Peng Wu、Bo Yang、Yongzhou Hu

  DOI：10.1016/j.ejmech.2015.05.025

  日期：2015.6

  A novel series of 4-alkynyl-quinoline derivatives were designed, synthesized and biologically evaluated for their PI3K alpha inhibitory activities and anti-proliferative effects against two cancer cell lines PC-3 and HCT-116. Most of them showed potent PI3K alpha inhibitory activities with IC50 values at low nanomolar level and good to excellent anti-proliferative effects against both cell lines. Among them, compound 15d, the most potent one, was selected for further biological evaluation. As a result, 15d displayed strong inhibitory activity against other class I PI3K isoforms (PI3K beta, PI3K gamma and PI3K delta) and mTOR with an acceptable kinase selectivity profile. Moreover, the western blot assay indicated that the phosphorylation of Akt, another downstream effector of PI3K, can be remarkably suppressed by 15d at cellular level. All these experimental results suggested that 15d is a potent PI3K/mTOR dual inhibitor and could serve as a promising lead compound for the development of anticancer agents. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Discovery of benzenesulfonamide derivatives as potent PI3K/mTOR dual inhibitors with in vivo efficacies against hepatocellular carcinoma
  作者：Ying Chen、Ling Zhang、Chao Yang、Jinsong Han、Chongqing Wang、Canhui Zheng、Youjun Zhou、Jiaguo Lv、Yunlong Song、Ju Zhu

  DOI：10.1016/j.bmc.2016.01.008

  日期：2016.3

  cancers, including hepatocellular carcinoma (HCC). The PI3K/mTOR dual inhibitors were proposed to have enhanced antitumor efficacies by targeting multiple points of the signaling pathway. We synthesized a series of propynyl-substituted benzenesulfonamide derivatives as PI3K/mTOR dual inhibitors. Compound 7k (NSC781406) was identified as a highly potent dual inhibitor, which exhibited potent tumor growth

  磷酸肌醇3-激酶（PI3K）/蛋白激酶B（AKT）/雷帕霉素的哺乳动物靶标（mTOR）信号通路与细胞活性有关。在包括肝细胞癌（HCC）在内的各种癌症中发现了该信号通路的异常。提出PI3K / mTOR双重抑制剂通过靶向信号传导途径的多个点而具有增强的抗肿瘤功效。我们合成了一系列丙炔基取代的苯磺酰胺衍生物作为PI3K / mTOR双重抑制剂。化合物7k（NSC781406）被鉴定为高效双重抑制剂，在肝细胞癌BEL-7404异种移植模型中显示出有效的肿瘤生长抑制作用。化合物7k可能是HCC的潜在治疗药物候选物。