3-(5,5-dicarbobenzyloxy-6-(3-(trifluoromethyl)phenyl)hexyl)-6,7-dihydroimidazo[4,5-d][1,3]diazepin-8(3H)-one | 273224-27-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑二氮卓类
• 英文名称: 3-(5,5-dicarbobenzyloxy-6-(3-(trifluoromethyl)phenyl)hexyl)-6,7-dihydroimidazo[4,5-d][1,3]diazepin-8(3H)-one
• 英文别名: Dibenzyl 2-[4-(8-oxo-4,7-dihydroimidazo[4,5-d][1,3]diazepin-3-yl)butyl]-2-[[3-(trifluoromethyl)phenyl]methyl]propanedioate
• CAS: 273224-27-4
• 化学式: C₃₅H₃₃F₃N₄O₅
• 分子量: 646.666
• InChiKey: HHVWCGDJRJBEIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  47
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  3-(5,5-dicarbobenzyloxy-6-(3-(trifluoromethyl)phenyl)hexyl)-6,7-dihydroimidazo[4,5-d][1,3]diazepin-8(3H)-one 在 sodium tetrahydroborate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以77%的产率得到3-(5,5-dicarbobenzyloxy-6-(3-(trifluoromethyl)phenyl)hexyl)coformycin aglycon
  参考文献：
  名称：

  AMP Deaminase Inhibitors. 4. Further N3-Substituted Coformycin Aglycon Analogues:  N3-Alkylmalonates as Ribose 5‘-Monophosphate Mimetics

  摘要：

  AMP deaminase (AMPDA) inhibitors increase the levels of extracellular adenosine and preserve intracellular adenylate pools in cellular models of ATP depletion and therefore represent a potential new class of antiischemic drugs. Recently we reported that replacement of the ribose 5'-monophosphate component of the very potent transition-state analogue AMPDA inhibitor coformycin monophosphate (1) with a simple alkylcarboxy group resulted in potent, selective, and cell-penetrating AMPDA inhibitors. Here we report that replacement of this alkylcarboxy group with an a-substituted alkylmalonic acid resulted in enhanced inhibitor potency. The lead compound, 3-(5,5-dicarboxy-6-(3-(trifluoromethyl)phenyl)-n-hexyl)coformation aglycon (21), exhibited an AMPDA K-i of 0.029 mu M which is (3 x 10(5))-fold lower than the K-M for the natural substrate AMP. A comparison of inhibitory potencies shows that the diacid analogues with cr-benzyl substituents are 2-10-fold more inhibitory than similar monoacid-monoester monoester-monoamide, or diester derivatives. Finally, these diacid analogues are 2-40-fold more potent inhibitors than the corresponding monocarboxylates.

  DOI：

  10.1021/jm9905413
• 作为产物：
  描述：

  3-(三氟甲基)溴苄 在 sodium hydride 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 3-(5,5-dicarbobenzyloxy-6-(3-(trifluoromethyl)phenyl)hexyl)-6,7-dihydroimidazo[4,5-d][1,3]diazepin-8(3H)-one
  参考文献：
  名称：

  AMP Deaminase Inhibitors. 4. Further N3-Substituted Coformycin Aglycon Analogues:  N3-Alkylmalonates as Ribose 5‘-Monophosphate Mimetics

  摘要：

  AMP deaminase (AMPDA) inhibitors increase the levels of extracellular adenosine and preserve intracellular adenylate pools in cellular models of ATP depletion and therefore represent a potential new class of antiischemic drugs. Recently we reported that replacement of the ribose 5'-monophosphate component of the very potent transition-state analogue AMPDA inhibitor coformycin monophosphate (1) with a simple alkylcarboxy group resulted in potent, selective, and cell-penetrating AMPDA inhibitors. Here we report that replacement of this alkylcarboxy group with an a-substituted alkylmalonic acid resulted in enhanced inhibitor potency. The lead compound, 3-(5,5-dicarboxy-6-(3-(trifluoromethyl)phenyl)-n-hexyl)coformation aglycon (21), exhibited an AMPDA K-i of 0.029 mu M which is (3 x 10(5))-fold lower than the K-M for the natural substrate AMP. A comparison of inhibitory potencies shows that the diacid analogues with cr-benzyl substituents are 2-10-fold more inhibitory than similar monoacid-monoester monoester-monoamide, or diester derivatives. Finally, these diacid analogues are 2-40-fold more potent inhibitors than the corresponding monocarboxylates.

  DOI：

  10.1021/jm9905413