N,N-dimethyl-(8-carbamoyl-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)ethanamide | 1161825-71-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑四嗪类
• 英文名称: N,N-dimethyl-(8-carbamoyl-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)ethanamide
• 英文别名: N,N-Dimethyl (8-Carbamoyl-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)ethanamide；3-[2-(dimethylamino)-2-oxoethyl]-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide
• CAS: 1161825-71-3
• 化学式: C₉H₁₁N₇O₃
• 分子量: 265.231
• InChiKey: LULCUBZLVBTNMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-N-hydroxymethyl temozolomide 在 N-甲基吗啉 、 盐酸 、 水 、 氯甲酸异丙酯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 46.0h， 生成 N,N-dimethyl-(8-carbamoyl-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)ethanamide
  参考文献：
  名称：

  [EN] 3-SUBSTITUTED-4-0X0-3, 4-DIHYDRO-IMIDAZO- [5, 1-D] [1,2,3,5] -TETRAZINE-8-CARBOXYLIC ACID AMIDES AS ANTICANCER AGENTS
  [FR] AMIDES D'ACIDES 4-OXO-3,4-DIHYDROIMIDAZO[5,1-D][1,2,3,5-TÉTRAZINE-8-CARBOXYLIQUES SUBSTITUÉS EN POSITION 3 ET LEUR UTILISATION

  摘要：

  公开号：

  WO2009077741A3

文献信息

• Antitumor imidazo[5,1-d]-1,2,3,5-tetrazines: compounds modified at the 3-position overcome resistance in human glioblastoma cell lines
  作者：David Cousin、Jihong Zhang、Marc G. Hummersone、Charles S. Matthews、Mark Frigerio、Tracey D. Bradshaw、Malcolm F. G. Stevens

  DOI：10.1039/c6md00384b

  日期：——

  Synthetic routes to 3-substituted imidazo[5,1-d]-1,2,3,5-tetrazines structurally related to temozolomide were explored. Interaction of 4-diazoimidazole-5-carboxamide with an isocyanate afforded high product yields when the isocyanate was available in acceptable purity. Alternatively, alkylation of the nor-temozolomide anion afforded high yields of new imidazotetrazines. Several compounds, evaluated

  探索了与替莫唑胺结构相关的3-取代的咪唑并[5,1- d ] -1,2,3,5-四嗪的合成途径。当以可接受的纯度获得异氰酸酯时，4-重氮咪唑-5-羧酰胺与异氰酸酯的相互作用提供了高产物收率。可选地，正-替唑啉酰亚胺阴离子的烷基化提供了高产率的新的咪唑并四嗪。针对含有匹配的MGMT±胶质瘤细胞系的一组化合物评估的几种化合物，无论MGMT的状态如何，均表现出相同的抑制活性。N3-炔丙基-咪唑并四嗪（10m）被优先作为替莫唑胺的替代品，后者能够绕过耐药机制。在Taq聚合酶测定法10m像替莫唑胺及其开环对应物MTIC一样，在三个和五个鸟嘌呤残基簇上的烷基化DNA；在哌啶裂解试验中检测到鸟嘌呤N-7位的共价修饰。化合物10m没有交联DNA，但是通过γ-H2AX检测证明诱导了双链断裂。炔丙基取代的咪唑三嗪（13g）显示出与10m相当的活性，表明新的咪唑四嗪的双环核开环可能是活性所必需的。
• 3-Substituted-4-Oxo-3,4-Dihydro-Imidazo[5,1-d][1,2,3,5-Tetrazine-8-Carboxylic Acid Amides and Their Use
  申请人：Stevens Malcolm Francis Graham

  公开号：US20100286088A1

  公开（公告）日：2010-11-11

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain 3-substituted-4-oxo-3,4-dihydro-imidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylic acid amide (collectively referred to herein as 3TM compounds). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit cell proliferation, and in the treatment of proliferative disorders such as cancer, etc., and methods of preparing such compounds.

  本发明涉及治疗化合物领域，更具体地涉及某些3-取代-4-氧代-3,4-二氢咪唑[5,1-d][1,2,3,5]四嗪-8-羧酸酰胺（统称为3TM化合物）。本发明还涉及包含这种化合物的制药组合物，以及在体内外使用这种化合物和组合物来抑制细胞增殖，在治疗增生性疾病如癌症等方面的应用，以及制备这种化合物的方法。
• 3-substituted-4-oxo-3,4-dihydro-imidazo[5,1-d][1,2,3,5-tetrazine-8-carboxylic acid amides and their use
  申请人：Stevens Malcolm Francis Graham

  公开号：US08450479B2

  公开（公告）日：2013-05-28

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain 3-substituted-4-oxo-3,4-dihydro-imidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylic acid amide (collectively referred to herein as 3TM compounds). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit cell proliferation, and in the treatment of proliferative disorders such as cancer, etc., and methods of preparing such compounds.

  本发明涉及治疗化合物领域，更具体地涉及某些3-取代-4-氧代-3,4-二氢咪唑[5,1-d][1,2,3,5]四嗪-8-羧酸酰胺（统称为3TM化合物）。本发明还涉及包含这种化合物的制药组合物，以及在体内外使用这种化合物和组合物来抑制细胞增殖，治疗增殖性疾病如癌症等，以及制备这种化合物的方法。
• 3-Substituted-4-Oxo-3,4-Dihydro-Imidazo[5,1-d]1,2,3,5-Tetrazine-8-Carboxylic Acid Amides and Their Use
  申请人：Pharminox Limited

  公开号：US20130338104A1

  公开（公告）日：2013-12-19

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain 3-substituted-4-oxo-3,4-dihydro-imidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylic acid amide (collectively referred to herein as 3TM compounds). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit cell proliferation, and in the treatment of proliferative disorders such as cancer, etc., and methods of preparing such compounds.

  本发明涉及治疗化合物领域，更具体地涉及某些3-取代-4-氧代-3,4-二氢咪唑[5,1-d][1,2,3,5]四唑-8-羧酸酰胺（以下统称为3TM化合物）。本发明还涉及包含这种化合物的制药组合物，以及在体内外使用这种化合物和组合物来抑制细胞增殖，治疗增生性疾病如癌症等的用途，以及制备这种化合物的方法。
• US8450479B2
  申请人：——

  公开号：US8450479B2

  公开（公告）日：2013-05-28