4-((2-((1-(Chloromethyl)-3-((5,6,7-trimethoxy-1H-indol-2-yl)carbonyl)-2,3-dihydro-1H-benzo[e]indol-5-yl)amino)-1-methyl-2-oxoethyl)amino)-N-(2-(dimethylamino)ethyl)-3,5-bis(hydroxy(oxido)amino)benzamide hydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((2-((1-(Chloromethyl)-3-((5,6,7-trimethoxy-1H-indol-2-yl)carbonyl)-2,3-dihydro-1H-benzo[e]indol-5-yl)amino)-1-methyl-2-oxoethyl)amino)-N-(2-(dimethylamino)ethyl)-3,5-bis(hydroxy(oxido)amino)benzamide hydrochloride
• 英文别名: 4-[[1-[[1-(chloromethyl)-3-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-1,2-dihydrobenzo[e]indol-5-yl]amino]-1-oxopropan-2-yl]amino]-N-[2-(dimethylamino)ethyl]-3,5-dinitrobenzamide
• 化学式: C₃₉H₄₁ClN₈O₁₀
• 分子量: 817.255
• InChiKey: KHWHDYUTJNRFFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  58
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  229
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  5-amino-1-(chloromethyl)-<(5,6,7-trimethoxyindol-2-yl)carbonyl>-1,2-dihydro-3H-benzindole 、 2-<<4-carbamoyl>-2,6-dinitrophenyl>amino>propanoic acid hydrochloride 在 2,4-滴二甲胺盐 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 反应 4.0h， 生成 4-((2-((1-(Chloromethyl)-3-((5,6,7-trimethoxy-1H-indol-2-yl)carbonyl)-2,3-dihydro-1H-benzo[e]indol-5-yl)amino)-1-methyl-2-oxoethyl)amino)-N-(2-(dimethylamino)ethyl)-3,5-bis(hydroxy(oxido)amino)benzamide hydrochloride
  参考文献：
  名称：

  N-Substituted 2-(2,6-Dinitrophenylamino)propanamides:  Novel Prodrugs That Release a Primary Amine via Nitroreduction and Intramolecular Cyclization

  摘要：

  A series of N-dinitrophenylamino acid amides [(4-CONHZ-2,6-diNO(2)Ph)N(R)C(X,Y)CONHPhOMe] were prepared as potential bioreductive prodrugs and reduced radiolytically to study their rates of subsequent intramolecular cyclization. Compounds bearing a free NH group (R = H) underwent rapid cyclization in neutral aqueous buffers (t(1/2) < 1 min) following 4-electron reduction, with the generation of a N-hydroxydihydroquinoxalinone and concomitant release of 4-methoxyaniline. Amine release from analogous N-methyl analogues (R = Me) was relatively slow. These results are consistent-with intramolecular cyclization of a monohydroxylamine intermediate. The high rates of cyclization/extrusion by these very electron-deficient hydroxylamines suggest that the process is greatly accelerated by the presence of an H-bonding "conformational lock" between the anilino NH group and the adjacent o-nitro group (Kirk and Cohen, 1972). Changes in the phenylcarboxamide side chain or in C-methylation in the linking chain had little effect-on the rate of cyclization. The model compounds had 1-electron reduction potentials in the range appropriate for cellular reduction (-373 mV for a measured example) and appeared suitable for development as prodrugs that release amine-based effecters following enzymic or radiolytic reduction. Prodrug examples containing 4-aminoaniline mustard and 5-amino-1-(chloromethyl)benz[e]indoline alkylating units were evaluated but were not activated efficiently by cellular nitroreductases. However, cell killing by the radiation-induced reduction of the latter prodrug was demonstrated.

  DOI：

  10.1021/jm960783s