2-((4-((4-chlorophenyl)sulfonyl)piperazin-1-yl)methyl)chromeno[4,3-c]pyrazol-4(2H)-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 2-((4-((4-chlorophenyl)sulfonyl)piperazin-1-yl)methyl)chromeno[4,3-c]pyrazol-4(2H)-one
• 英文别名: 2-[[4-(4-Chlorophenyl)sulfonylpiperazin-1-yl]methyl]chromeno[4,3-c]pyrazol-4-one；2-[[4-(4-chlorophenyl)sulfonylpiperazin-1-yl]methyl]chromeno[4,3-c]pyrazol-4-one
• 化学式: C₂₁H₁₉ClN₄O₄S
• 分子量: 458.925
• InChiKey: ASBPXYDMJRHBDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  93.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-hydroxycoumarin 在 三氯氧磷 作用下， 以 乙醇 为溶剂， 生成 2-((4-((4-chlorophenyl)sulfonyl)piperazin-1-yl)methyl)chromeno[4,3-c]pyrazol-4(2H)-one
  参考文献：
  名称：

  Development of novel chromeno[4,3-c]pyrazol-4(2H)-one derivates bearing sulfonylpiperazine as antitumor inhibitors targeting PI3Kα

  摘要：

  PI3K signal pathway plays a vital role in cellular functions and becomes an attractive approach for cancer therapy. Herein, a new series of novel chromeno[4,3-c]pyrazol-4(2H)-one derivatives bearing sulfonylpiperazine based on the PI3K inhibitors and our previous research. They were screened for their PI3K inhibitory activities and anticancer effects in vitro. Biological studies indicated that compound 7m revealed the remarkable antiproliferative activity (IC50 ranging from 0.03 to 0.09 mu M) against four cancer cell lines (A549, Huh7, HL60 and HCT-116). Besides, compound 7m displayed a certain selective for PI3K alpha (IC50 = 0.009 mu M) over PI3K beta, gamma and delta, and meanwhile, it can remarkable decreased the expression level of p-Akt (Ser473) and p-S6K. In addition, compound 7m could not only induce HCT-116 cell arrest at G1 phase in a dose-dependent manner, but also induce cell apoptosis via upregulation of Bax and cleaved-caspase 3/9, and downregulation of Bcl-2. Besides, compound 7m can remarkably inhibit the growth of tumor in vivo. The above results suggested that compound 7m could be considered as a promising PI3K alpha inhibitor. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111630

文献信息

• Development of novel chromeno[4,3-c]pyrazol-4(2H)-one derivates bearing sulfonylpiperazine as antitumor inhibitors targeting PI3Kα
  作者：Yong Yin、Shao Sha、Xun Wu、She-Feng Wang、Fang Qiao、Zhong-Cheng Song、Hai-Liang Zhu

  DOI：10.1016/j.ejmech.2019.111630

  日期：2019.11

  PI3K signal pathway plays a vital role in cellular functions and becomes an attractive approach for cancer therapy. Herein, a new series of novel chromeno[4,3-c]pyrazol-4(2H)-one derivatives bearing sulfonylpiperazine based on the PI3K inhibitors and our previous research. They were screened for their PI3K inhibitory activities and anticancer effects in vitro. Biological studies indicated that compound 7m revealed the remarkable antiproliferative activity (IC50 ranging from 0.03 to 0.09 mu M) against four cancer cell lines (A549, Huh7, HL60 and HCT-116). Besides, compound 7m displayed a certain selective for PI3K alpha (IC50 = 0.009 mu M) over PI3K beta, gamma and delta, and meanwhile, it can remarkable decreased the expression level of p-Akt (Ser473) and p-S6K. In addition, compound 7m could not only induce HCT-116 cell arrest at G1 phase in a dose-dependent manner, but also induce cell apoptosis via upregulation of Bax and cleaved-caspase 3/9, and downregulation of Bcl-2. Besides, compound 7m can remarkably inhibit the growth of tumor in vivo. The above results suggested that compound 7m could be considered as a promising PI3K alpha inhibitor. (C) 2019 Elsevier Masson SAS. All rights reserved.