5-diazoimidazole-4-carboxamide | 1314929-56-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5-diazoimidazole-4-carboxamide
• 英文别名: 5-Diazenyl-1H-imidazole-4-carboxamide；4-diazenyl-1H-imidazole-5-carboxamide
• CAS: 1314929-56-0
• 化学式: C₄H₅N₅O
• mdl: MFCD19206065
• 分子量: 139.117
• InChiKey: IRJLFDHRTDDHFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-diazoimidazole-4-carboxamide 、 异氰酸异丙酯 以 二甲基亚砜 为溶剂， 反应 24.0h， 以29%的产率得到8-carbamoyl-3-(i-propyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one
  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

• Causative agent of vascular pain among photodegradation products of dacarbazine
  作者：Mariko Asahi、Ryo Matsushita、Masami Kawahara、Tomoyuki Ishida、Chie Emoto、Nagao Suzuki、Osamu Kataoka、Chisato Mukai、Miyoji Hanaoka、Junko Ishizaki、Koichi Yokogawa、Ken'ichi Miyamoto

  DOI：10.1211/002235702320266280

  日期：2010.2.18

  The photodegradation products of the anticancer drug, dacarbazine, cause adverse reactions including local venous pain when injected intravenously. In this study, we attempted to identify which of these products is responsible. We synthesized or purchased five photodegradation products of dacarbazine (dimethylamine, 5-diazoimidazole-4-carboxamide (Diazo-IC), 4-carbamoylimidazolium-5-olate, 5-carbamoyl-2-(4-carbamoylimidazol-5-ylazo) imidazolium-5-olate and 2-azahypoxanthine) and examined the pain reaction induced by their intraperitoneal administration in mice using an abdominal stretching or constriction assay. Only Diazo-IC clearly induced pain reaction in mice in a dose-dependent manner, the other products caused no pain reaction. The threshold concentration for pain reaction in mice was estimated to be about 0.1 mg mL−1. While diclofenac sodium significantly reduced acetic-acid-induced pain reaction in mice, it did not influence those induced by Diazo-IC. This result suggests that the mechanism of Diazo-IC-induced pain is different from that of acetic-acid-induced inflammatory pain. Dacarbazine itself produced marked relaxation of rat thoracic aorta strips in a concentration-dependent manner, but there was no difference between the activity of dacarbazine and its photo-exposed solution, so constriction or relaxation of blood vessels is unlikely to be a factor in the pain reaction. In conclusion, Diazo-IC generated by photodegradation of dacarbazine solution causes the side-effect of venous pain. Dacarbazine solution that has turned pink should not be used, because Diazo-IC is an intermediate in the formation of the reddish product, 5-carbamoyl-2-(4-carbamoylimidazol-5-ylazo) imidazolium-5-olate. Drip infusion preparations of dacarbazine should be shielded from light.

  摘要 抗癌药物达卡巴嗪的光降解产物在静脉注射时会引起局部静脉疼痛等不良反应。本研究试图确定哪种光降解产物是导致这些不良反应的原因。我们合成或购买了达卡巴嗪的五种光降解产物（二甲胺，5-重氮咪唑-4-甲酰胺（重氮-IC），4-氨基咪唑-5-酮酸酯，5-氨基甲酰基-2-(4-氨基咪唑-5-基偶氮) 咪唑-5-酮酸酯和2-氮杂次黄嘌呤），并通过腹腔注射在小鼠体内引起的腹部伸展或收缩反应来检查其引起的疼痛反应。只有重氮-IC明显以剂量依赖方式在小鼠体内引起疼痛反应，其他产物没有引起疼痛反应。小鼠疼痛反应的阈浓度估计约为0.1毫克/毫升。虽然双氯芬酸钠显著减少了乙酸诱导的小鼠疼痛反应，但对重氮-IC引起的疼痛反应没有影响。这一结果表明，重氮-IC引起的疼痛机制与乙酸诱导的炎症性疼痛机制不同。达卡巴嗪本身以浓度依赖方式显著放松大鼠胸主动脉条，但达卡巴嗪及其光照暴露溶液的活性没有差异，因此血管的收缩或松弛不太可能是疼痛反应的因素。总之，达卡巴嗪溶液的光降解产生的重氮-IC导致静脉疼痛的副作用。已变成粉红色的达卡巴嗪溶液不应使用，因为重氮-IC是形成红色产物5-氨基甲酰基-2-(4-氨基咪唑-5-基偶氮) 咪唑-5-酮酸酯的中间体。达卡巴嗪的滴注制剂应避免光照。
• [EN] 3-SUBSTITUTED-4-0X0-3, 4-DIHYDRO-IMIDAZO- [5, 1-D] [1,2,3,5] -TETRAZINE-8-CARBOXYLIC ACID AMIDES AS ANTICANCER AGENTS<br/>[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
  申请人：PHARMINOX LTD

  公开号：WO2009077741A3

  公开（公告）日：2009-12-03