4-oxo-3-(prop-2-yn-1-yl)-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylic acid | 1259489-28-5

• 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: 4-oxo-3-(prop-2-yn-1-yl)-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylic acid
• 英文别名: 4-oxo-3-(prop-2-ynyl)-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylic acid；4-Oxo-3-(prop-2-ynyl)-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylic acid；4-oxo-3-prop-2-ynylimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylic acid
• CAS: 1259489-28-5
• 化学式: C₈H₅N₅O₃
• 分子量: 219.159
• InChiKey: ANESUTZTIDGLFL-UHFFFAOYSA-N

物化性质

• 沸点：
  499.9±51.0 °C(predicted)
• 密度：
  1.67±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-oxo-3-(prop-2-yn-1-yl)-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylic acid 在 三氟甲磺酸酐 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三苯基氧化膦 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.41h， 生成 8-(1H-benzo[d]imidazol-2-yl)-3-(prop-2-ynyl)imidazo[5,1-d][1,2,3,5]tetrazin-4(3H)-one
  参考文献：
  名称：

  [EN] 3-SUBSTITUTED-8-SUBSTITUTED-3H IMIDAZO[5,1-D][1,2,3,5-TETRAZIN-4-ONE COMPOUNDS AND THEIR USE
  [FR] COMPOSÉS 3H-IMIDAZO[5,1-D][1,2,3,5-TÉTRAZIN-4-ONE 3-SUBSTITUÉS-8-SUBSTITUÉS ET LEUR UTILISATION

  摘要：

  本发明一般涉及治疗化合物领域，更具体地涉及以下公式的3-取代-8-取代-3H-咪唑[5,1-d][1,2,3,5]四唑-4-酮化合物，其中-A和-B如本文所定义（统称为38TM化合物）：（1）。本发明还涉及包含这种化合物的药物组合物，以及利用这种化合物和组合物在体外和体内抑制细胞增殖，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。

  公开号：

  WO2010149968A1
• 作为产物：
  描述：

  8-carbamoyl-3-propargylimidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one 在 三氟乙酸 、 sodium nitrite 作用下， 以 水 为溶剂， 以72 %的产率得到4-oxo-3-(prop-2-yn-1-yl)-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylic acid
  参考文献：
  名称：

  [EN] IMIDAZOTETRAZINE COMPOUNDS AND TREATMENT OF TMZ-RESISTANT CANCERS
  [FR] COMPOSÉS D'IMIDAZOTÉTRAZINE ET TRAITEMENT DE CANCERS RÉSISTANTS AU TMZ

  摘要：

  Imidazotetrazines were designed to evade resistance byO6-methylguanine DNA methyltransferase (MGMT) while retaining suitable hydrolytic stability, allowing for effective prodrug activation and biodistribution. One compound, called TABZ, exhibits activity against cancer cells irrespective of MGMT expression and MMR status. TABZ has comparable blood-brain barrier penetrance and comparable hematological toxicity relative to TMZ, while also matching its maximum tolerated dose (MTD) in mice when dosed once-per-day over five days. The activity of TABZ is independent of the two principal mechanisms suppressing the effectiveness of TMZ, making it a promising new candidate for the treatment of GBM, especially those that are TMZ resistant.

  公开号：

  WO2023150569A1

文献信息

• 3-Substituted-8-Substituted-3H-Imidazo[5,1-d][1,2,3,5]tetrazin-4-one Compounds and Their Use
  申请人：Hummersone Marc Geoffery

  公开号：US20120083513A1

  公开（公告）日：2012-04-05

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to 3-substituted-8-substituted-3H-imidazo[5,1-d][1,2,3,5]tetrazin-4-one compounds of the following formula, wherein -A and —B are as defined herein (collectively referred to herein as 38TM 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，更具体地涉及以下式子的3-取代-8-取代-3H-咪唑[5,1-d][1,2,3,5]四唑-4-酮化合物，其中-A和—B在此定义（统称为38TM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-8-substituted-3H-imidazo[5,1-d][1,2,3,5]tetrazin-4-one compounds and their use
  申请人：Hummersone Marc Geoffery

  公开号：US09024018B2

  公开（公告）日：2015-05-05

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to 3-substituted-8-substituted-3H-imidazo[5,1-d][1,2,3,5]tetrazin-4-one compounds of the following formula, wherein -A and —B are as defined herein (collectively referred to herein as 38TM 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，更具体地涉及以下式子的3-取代-8-取代-3H-咪唑[5,1-d][1,2,3,5]四唑-4-酮化合物（统称为38TM化合物），其中-A和-B如本文所定义。本发明还涉及包括此类化合物的制药组合物以及使用此类化合物和组合物在体外和体内抑制细胞增殖，治疗增殖性疾病如癌症等的用途，以及制备此类化合物的方法。
• 3-SUBSTITUTED-8-SUBSTITUTED-3H IMIDAZO[5,1-D][1,2,3,5-TETRAZIN-4-ONE COMPOUNDS AND THEIR USE
  申请人：Pharminox Limited

  公开号：EP2445915A1

  公开（公告）日：2012-05-02
• US9024018B2
  申请人：——

  公开号：US9024018B2

  公开（公告）日：2015-05-05
• [EN] 3-SUBSTITUTED-8-SUBSTITUTED-3H IMIDAZO[5,1-D][1,2,3,5-TETRAZIN-4-ONE COMPOUNDS AND THEIR USE<br/>[FR] COMPOSÉS 3H-IMIDAZO[5,1-D][1,2,3,5-TÉTRAZIN-4-ONE 3-SUBSTITUÉS-8-SUBSTITUÉS ET LEUR UTILISATION
  申请人：PHARMINOX LTD

  公开号：WO2010149968A1

  公开（公告）日：2010-12-29

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to 3-substituted-8-substituted-3H-imidazo[5,1-d][1,2,3,5]tetrazin-4-one compounds of the following formula, wherein -A and -B are as defined herein (collectively referred to herein as 38TM compounds): (1). 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.

  本发明一般涉及治疗化合物领域，更具体地涉及以下公式的3-取代-8-取代-3H-咪唑[5,1-d][1,2,3,5]四唑-4-酮化合物，其中-A和-B如本文所定义（统称为38TM化合物）：（1）。本发明还涉及包含这种化合物的药物组合物，以及利用这种化合物和组合物在体外和体内抑制细胞增殖，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。