7-bromo-4-trifluoroacetamido-8-methyl-1,2,3,4-tetrahydropyrido[1,2-a]benzimidazole | 410523-48-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 7-bromo-4-trifluoroacetamido-8-methyl-1,2,3,4-tetrahydropyrido[1,2-a]benzimidazole
• 英文别名: N-(7-bromo-8-methyl-1,2,3,4-tetrahydropyrido[1,2-a]benzimidazol-4-yl)-2,2,2-trifluoroacetamide
• CAS: 410523-48-7
• 化学式: C₁₄H₁₃BrF₃N₃O
• 分子量: 376.176
• InChiKey: UXZQPLFXUDOZET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  46.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-bromo-4-trifluoroacetamido-8-methyl-1,2,3,4-tetrahydropyrido[1,2-a]benzimidazole 在 硝酸 、 乙酸酐 作用下， 反应 1.5h， 以67%的产率得到7-bromo-4-trifluoroacetamido-8-methyl-6-nitro-1,2,3,4-tetrahydropyrido[1,2-a]benzimidazole
  参考文献：
  名称：

  A Comprehensive Study of the Active Site Residues of DT-Diaphorase:  Rational Design of Benzimidazolediones as DT-Diaphorase Substrates

  摘要：

  A series of quinone substrates were modeled into the active site of human DT-diaphorase and minimized. Correlation of these models with the substrate specificity k(cat)/K-m provided insights into the structural requirements of quinone substrates. The W105, F106, and H194 residues can influence the position of the quinone substrate in the active site resulting in formation of one of the two possible Michael anions resulting from hydride transfer from FADH(2). Electron withdrawing groups on the substrate can stabilize these anions resulting in excellent substrate specificity. Inspection of models indicated that the W-105 and F-106 residues form parallel walls that will accommodate large polycyclic substrates. Thus excellent polycyclic substrates of DT-diaphorase were designed. However, the placement of tetrahedral centers on these polycyclic substrates interfered with the W-105 and the F-106 residues resulting in their exclusion from the active site. The histidine (H194) residue permits recognition of substrate enantiomers as a result of hydrogen bonding interactions. As a result of this study, it will be possible to design poor to excellent substrates of DT-diaphorase and take advantage of varying levels of this enzyme in histologically different cancers.

  DOI：

  10.1021/jm0104365
• 作为产物：
  描述：

  4-trifluoroacetamido-8-methyl-1,2,3,4-tetrahydropyrido[1,2-a]benzimidazole 在 溴 、 溶剂黄146 作用下， 反应 0.42h， 以67%的产率得到7-bromo-4-trifluoroacetamido-8-methyl-1,2,3,4-tetrahydropyrido[1,2-a]benzimidazole
  参考文献：
  名称：

  A Comprehensive Study of the Active Site Residues of DT-Diaphorase:  Rational Design of Benzimidazolediones as DT-Diaphorase Substrates

  摘要：

  A series of quinone substrates were modeled into the active site of human DT-diaphorase and minimized. Correlation of these models with the substrate specificity k(cat)/K-m provided insights into the structural requirements of quinone substrates. The W105, F106, and H194 residues can influence the position of the quinone substrate in the active site resulting in formation of one of the two possible Michael anions resulting from hydride transfer from FADH(2). Electron withdrawing groups on the substrate can stabilize these anions resulting in excellent substrate specificity. Inspection of models indicated that the W-105 and F-106 residues form parallel walls that will accommodate large polycyclic substrates. Thus excellent polycyclic substrates of DT-diaphorase were designed. However, the placement of tetrahedral centers on these polycyclic substrates interfered with the W-105 and the F-106 residues resulting in their exclusion from the active site. The histidine (H194) residue permits recognition of substrate enantiomers as a result of hydrogen bonding interactions. As a result of this study, it will be possible to design poor to excellent substrates of DT-diaphorase and take advantage of varying levels of this enzyme in histologically different cancers.

  DOI：

  10.1021/jm0104365