1,2,3,4,8,9,10,11-Octahydro-dipyrido<1,2-a:1',2'-a'>benzo<1,2-d:5,4-d>diimidazol | 7099-37-8

• 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: 1,2,3,4,8,9,10,11-Octahydro-dipyrido<1,2-a:1',2'-a'>benzo<1,2-d:5,4-d>diimidazol
• 英文别名: 4,10,14,20-Tetrazapentacyclo[11.7.0.03,11.04,9.015,20]icosa-1(13),2,9,11,14-pentaene；4,10,14,20-tetrazapentacyclo[11.7.0.03,11.04,9.015,20]icosa-1(13),2,9,11,14-pentaene
• CAS: 7099-37-8
• 化学式: C₁₆H₁₈N₄
• 分子量: 266.346
• InChiKey: PXSXIJKJLBUXLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,2,3,4,8,9,10,11-Octahydro-dipyrido<1,2-a:1',2'-a'>benzo<1,2-d:5,4-d>diimidazol 在 硫酸 、 硝酸 作用下， 反应 0.25h， 以50%的产率得到6-nitro-1,2,3,4,8,9,10,11-octahydrodipyrido[1,2-a:1',2'-a']benzo[1,2-d:5,4-d']diimidazole
  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：

  7-nitro-8-piperidino-1,2,3,4-tetrahydro-benz[4,5]imidazo[1,2-a]pyridine 在 盐酸 、 甲醇 、 镍 作用下， 50.0~55.0 ℃ 、4.9 MPa 条件下， 生成 1,2,3,4,8,9,10,11-Octahydro-dipyrido<1,2-a:1',2'-a'>benzo<1,2-d:5,4-d>diimidazol
  参考文献：
  名称：

  吡啶和哌啶-（1'：2'-1：2）苯并咪唑系列的合成

  摘要：

  DOI：

  10.1039/jr9550003275

文献信息

• One-pot double intramolecular homolytic aromatic substitution routes to dialicyclic ring fused imidazobenzimidazolequinones and preliminary analysis of anticancer activity
  作者：Vincent Fagan、Sarah Bonham、Michael P. Carty、Fawaz Aldabbagh

  DOI：10.1039/c003511d

  日期：——

  Bu3SnH/1,1′-azobis(cyclohexanecarbonitrile) (ACN)-mediated five, six, and seven-membered double alkyl radical cyclizations onto imidazo[5,4-f]benzimidazole and imidazo[4,5-f]benzimidazole are described. The quinone derivatives evaluated show selective toxicity towards human cervical (HeLa) and prostate (DU145) cancer cell lines (with negligible toxicity towards a normal human cell line, GM00637). Only the Fremy oxidation of the 6-aminoimidazo[5,4-f]benzimidazole gave iminoquinone, which showed high specificity towards the prostate cancer cell line (DU145).

  介绍了 Bu3SnH/1,1′-偶氮双（环己烷腈）（ACN）介导的咪唑并[5,4-f]苯并咪唑和咪唑并[4,5-f]苯并咪唑的五元、六元和七元双烷基环化反应。所评估的醌衍生物对人类宫颈癌（HeLa）和前列腺癌（DU145）细胞系具有选择性毒性（对正常人细胞系 GM00637 的毒性可忽略不计）。只有 6-氨基咪唑并[5,4-f]苯并咪唑的 Fremy 氧化反应产生了亚氨基醌，它对前列腺癌细胞株（DU145）具有高度特异性。
• A Comprehensive Study of the Active Site Residues of DT-Diaphorase:  Rational Design of Benzimidazolediones as DT-Diaphorase Substrates
  作者：Ali Suleman、Edward B. Skibo

  DOI：10.1021/jm0104365

  日期：2002.3.1

  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.
• Syntheses in the pyrido- and piperido-(1′ : 2′-1 : 2)benziminazole series
  作者：K. H. Saunders

  DOI：10.1039/jr9550003275

  日期：——