2-(5-Methoxy-1-methyl-4,7-dioxoindol-3-yl)-4-methylthiazole | 162376-39-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-(5-Methoxy-1-methyl-4,7-dioxoindol-3-yl)-4-methylthiazole
• 英文别名: 5-methoxy-1-methyl-3-(4-methyl-1,3-thiazol-2-yl)indole-4,7-dione
• CAS: 162376-39-8
• 化学式: C₁₄H₁₂N₂O₃S
• 分子量: 288.327
• InChiKey: XAOBFMXDNXHENE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  89.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(5-Methoxy-1-methyl-4,7-dioxoindol-3-yl)-4-methylthiazole 在 氨 作用下， 以 二氯甲烷 为溶剂， 以92%的产率得到2-(5-Amino-1-methyl-4,7-dioxoindol-3-yl)-4-methylthiazole
  参考文献：
  名称：

  Synthesis and Biological Activity of Thiazolylindolequinones, Analogs of the Natural Product BE 10988

  摘要：

  A number of analogues of the naturally occurring thiazolylindolequinone BE 10988, a reported potent inhibitor of topoisomerase II, have been prepared and evaluated. The compounds were synthesized from 4-(benzyloxy)-S-methoxy-1-methylindole by appropriate substitution at the indole 3-position followed by standard thiazole ring-forming reactions. The toxicity of these potentially bioreductively activated indolequinones was measured in Chinese hamster V79 cells under aerobic and hypoxic conditions. In addition, toxicity was measured in a human breast cancer cell line that shows amplification of the topo II alpha gene and hypersensitivity to known topo II inhibitors such as mAMSA and mitoxantrone. Using a DNA decatenation assay, a comparison was also made of the inhibitory effects of BE 10988 and mitoxantrone on topo II activity.

  DOI：

  10.1021/jm00006a024
• 作为产物：
  描述：

  4-(benzyloxy)-5-methoxy-1-methylindole-3-thiocarboxamide 在 palladium on activated charcoal disodium hydrogenphosphate 、 potassium nitrososulfonate 、 氢气 作用下， 以 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 12.5h， 生成 2-(5-Methoxy-1-methyl-4,7-dioxoindol-3-yl)-4-methylthiazole
  参考文献：
  名称：

  Synthesis and Biological Activity of Thiazolylindolequinones, Analogs of the Natural Product BE 10988

  摘要：

  A number of analogues of the naturally occurring thiazolylindolequinone BE 10988, a reported potent inhibitor of topoisomerase II, have been prepared and evaluated. The compounds were synthesized from 4-(benzyloxy)-S-methoxy-1-methylindole by appropriate substitution at the indole 3-position followed by standard thiazole ring-forming reactions. The toxicity of these potentially bioreductively activated indolequinones was measured in Chinese hamster V79 cells under aerobic and hypoxic conditions. In addition, toxicity was measured in a human breast cancer cell line that shows amplification of the topo II alpha gene and hypersensitivity to known topo II inhibitors such as mAMSA and mitoxantrone. Using a DNA decatenation assay, a comparison was also made of the inhibitory effects of BE 10988 and mitoxantrone on topo II activity.

  DOI：

  10.1021/jm00006a024

文献信息

• Synthesis and Biological Activity of Thiazolylindolequinones, Analogs of the Natural Product BE 10988
  作者：Christopher J. Moody、Elizabeth Swann、Susan Houlbrook、Miriam A. Stephens、Ian J. Stratford

  DOI：10.1021/jm00006a024

  日期：1995.3

  A number of analogues of the naturally occurring thiazolylindolequinone BE 10988, a reported potent inhibitor of topoisomerase II, have been prepared and evaluated. The compounds were synthesized from 4-(benzyloxy)-S-methoxy-1-methylindole by appropriate substitution at the indole 3-position followed by standard thiazole ring-forming reactions. The toxicity of these potentially bioreductively activated indolequinones was measured in Chinese hamster V79 cells under aerobic and hypoxic conditions. In addition, toxicity was measured in a human breast cancer cell line that shows amplification of the topo II alpha gene and hypersensitivity to known topo II inhibitors such as mAMSA and mitoxantrone. Using a DNA decatenation assay, a comparison was also made of the inhibitory effects of BE 10988 and mitoxantrone on topo II activity.