4-(5-methyl-4,4-dioxo-1H-pyrazolo[4,3-c][2,1]benzothiazin-8-yl)benzamide | 1426683-43-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 4-(5-methyl-4,4-dioxo-1H-pyrazolo[4,3-c][2,1]benzothiazin-8-yl)benzamide
• CAS: 1426683-43-3
• 化学式: C₁₇H₁₄N₄O₃S
• 分子量: 354.389
• InChiKey: PXRULJZQXIUNTM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-溴-2-[(甲基磺酰基)氨基]苯甲酸甲酯 在 3,4-二氢-2H-吡喃 、 sodium hydride 、 potassium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 4-(5-methyl-4,4-dioxo-1H-pyrazolo[4,3-c][2,1]benzothiazin-8-yl)benzamide
  参考文献：
  名称：

  Structure-based discovery of cellular-active allosteric inhibitors of FAK

  摘要：

  In order to develop potent and selective focal adhesion kinase (FAK) inhibitors, synthetic studies on pyrazolo[ 4,3-c][2,1]benzothiazines targeted for the FAK allosteric site were carried out. Based on the X-ray structural analysis of the co-crystal of the lead compound, 8-(4-ethylphenyl)-5-methyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazine 4,4-dioxide 1 with FAK, we designed and prepared 1,5-dimethyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazin derivatives which selectively inhibited kinase activity of FAK without affecting seven other kinases. The optimized compound, N-(4-tert-butylbenzyl)-1,5-dimethyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazin-8-amine 4,4-dioxide 30 possessed significant FAK kinase inhibitory activities both in cell-free (IC50 = 0.64 mu M) and in cellular assays (IC50 = 7.1 mu M). These results clearly demonstrated a potential of FAK allosteric inhibitors as antitumor agents. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.047

文献信息

• Structure-based discovery of cellular-active allosteric inhibitors of FAK
  作者：Naoki Tomita、Yoko Hayashi、Shinkichi Suzuki、Yoshimasa Oomori、Yoshio Aramaki、Yoshihiro Matsushita、Misa Iwatani、Hidehisa Iwata、Atsutoshi Okabe、Yoshiko Awazu、Osamu Isono、Robert J. Skene、David J. Hosfield、Hiroshi Miki、Tomohiro Kawamoto、Akira Hori、Atsuo Baba

  DOI：10.1016/j.bmcl.2013.01.047

  日期：2013.3

  In order to develop potent and selective focal adhesion kinase (FAK) inhibitors, synthetic studies on pyrazolo[ 4,3-c][2,1]benzothiazines targeted for the FAK allosteric site were carried out. Based on the X-ray structural analysis of the co-crystal of the lead compound, 8-(4-ethylphenyl)-5-methyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazine 4,4-dioxide 1 with FAK, we designed and prepared 1,5-dimethyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazin derivatives which selectively inhibited kinase activity of FAK without affecting seven other kinases. The optimized compound, N-(4-tert-butylbenzyl)-1,5-dimethyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazin-8-amine 4,4-dioxide 30 possessed significant FAK kinase inhibitory activities both in cell-free (IC50 = 0.64 mu M) and in cellular assays (IC50 = 7.1 mu M). These results clearly demonstrated a potential of FAK allosteric inhibitors as antitumor agents. (C) 2013 Elsevier Ltd. All rights reserved.