5-Amino-1-[amino(methyl)carbamoyl]imidazole-4-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-Amino-1-[amino(methyl)carbamoyl]imidazole-4-carboxylic acid
• 英文别名: 5-amino-1-[amino(methyl)carbamoyl]imidazole-4-carboxylic acid
• 化学式: C₆H₉N₅O₃
• 分子量: 199.17
• InChiKey: WJHPLRBNHHYZQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  128
• 氢给体数：
  3
• 氢受体数：
  6

文献信息

• [EN] IMIDAZOTETRAZINE COMPOUNDS<br/>[FR] COMPOSÉS D'IMIDAZOTÉTRAZINE
  申请人：UNIV ILLINOIS

  公开号：WO2020033880A1

  公开（公告）日：2020-02-13

  New synthetic methods to provide access to previously unexplored functionality at the C8 position of imidazotetrazines. Through synthesis and evaluation of a suite of compounds with a range of aqueous stabilities (from 0.5 to 40 hours), a predictive model for imidazotetrazine hydrolytic stability based on the Hammett constant of the C8 substituent was derived. Promising compounds were identified that possess activity against a panel of GBM cell lines, appropriate hydrolytic and metabolic stability, and brain-to-serum ratios dramatically elevated relative to TMZ, leading to lower hematological toxicity profiles and superior activity to TMZ in a mouse model of GBM.

  新的合成方法提供了对咪唑四唑的C8位置以前未探索功能的访问。通过合成和评估一系列具有不同水稳定性（从0.5到40小时）的化合物，基于C8取代基的Hammett常数建立了咪唑四唑水解稳定性的预测模型。鉴定了具有活性的化合物，对一系列GBM细胞系具有活性，具有适当的水解和代谢稳定性，并且脑血清比例相对于TMZ显著升高，导致较低的血液毒性剖面和在GBM小鼠模型中优于TMZ的活性。