8-(6,8-dichloro-9-cyclopropyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-2-carbonyl)-3-methylimidazo[5,1-d][1,2,3,5]tetrazin-4(3H)-one

• 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: 8-(6,8-dichloro-9-cyclopropyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-2-carbonyl)-3-methylimidazo[5,1-d][1,2,3,5]tetrazin-4(3H)-one
• 英文别名: 8-(6,8-dichloro-9-cyclopropyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2-carbonyl)-3-methylimidazo[5,1-d][1,2,3,5]tetrazin-4-one
• 化学式: C₂₀H₁₇Cl₂N₇O₂
• 分子量: 458.307
• InChiKey: BJAIGCJCLUZMRY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  31
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-(6,8-dichloro-9-cyclopropyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-2-carbonyl)-3-methylimidazo[5,1-d][1,2,3,5]tetrazin-4(3H)-one 以 aq. phosphate buffer 为溶剂， 反应 12.0h， 以5.1%的产率得到(5-amino-1H-imidazol-4-yl)(6,8-dichloro-9-cyclopropyl-3,4-dihydro-1H-pyrido[3,4-b]indol-2(9H)-yl)methanone
  参考文献：
  名称：

  Temozolomide analogs with improved brain/plasma ratios – Exploring the possibility of enhancing the therapeutic index of temozolomide

  摘要：

  Temozolomide is a chemotherapeutic agent that is used in the treatment of glioblastoma and other malignant gliomas. It acts through DNA alkylation, but treatment is limited by its systemic toxicity and neutralization of DNA alkylation by upregulation of the O-6-methylguanine-DNA methyltransferase gene. Both of these limiting factors can be addressed by achieving higher concentrations of TMZ in the brain. Our research has led to the discovery of new analogs of temozolomide with improved brain: plasma ratios when dosed in vivo in rats. These compounds are imidazotetrazine analogs, expected to act through the same mechanism as temozolomide. With reduced systemic exposure, these new agents have the potential to improve efficacy and therapeutic index in the treatment of glioblastoma. (C) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.08.064
• 作为产物：
  描述：

  2,4-二氯苯肼盐酸盐 在 盐酸 、 4-二甲氨基吡啶 、 硫酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 copper diacetate 、 sodium hexamethyldisilazane 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 25.5h， 生成 8-(6,8-dichloro-9-cyclopropyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-2-carbonyl)-3-methylimidazo[5,1-d][1,2,3,5]tetrazin-4(3H)-one
  参考文献：
  名称：

  Temozolomide analogs with improved brain/plasma ratios – Exploring the possibility of enhancing the therapeutic index of temozolomide

  摘要：

  Temozolomide is a chemotherapeutic agent that is used in the treatment of glioblastoma and other malignant gliomas. It acts through DNA alkylation, but treatment is limited by its systemic toxicity and neutralization of DNA alkylation by upregulation of the O-6-methylguanine-DNA methyltransferase gene. Both of these limiting factors can be addressed by achieving higher concentrations of TMZ in the brain. Our research has led to the discovery of new analogs of temozolomide with improved brain: plasma ratios when dosed in vivo in rats. These compounds are imidazotetrazine analogs, expected to act through the same mechanism as temozolomide. With reduced systemic exposure, these new agents have the potential to improve efficacy and therapeutic index in the treatment of glioblastoma. (C) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.08.064