4-(5-Amino-1-methyl-4,7-dioxoindol-3-yl)-1,3-thiazole-2-carboxamide

• 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: 4-(5-Amino-1-methyl-4,7-dioxoindol-3-yl)-1,3-thiazole-2-carboxamide
• 化学式: C₁₃H₁₀N₄O₃S
• 分子量: 302.313
• InChiKey: VQVRACWMNPUNIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  149
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-苄氧基-5-甲氧基-1-甲基吲哚 在 disodium hydrogenphosphate 、 potassium nitrososulfonate 、 氨 、 sodium bromide 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 124.5h， 生成 4-(5-Amino-1-methyl-4,7-dioxoindol-3-yl)-1,3-thiazole-2-carboxamide
  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.