N-<4-phenyl>-2-<(4-carboxy-2,6-dinitrophenyl)amino>propanamide | 220903-73-1

• 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: N-<4-phenyl>-2-<(4-carboxy-2,6-dinitrophenyl)amino>propanamide
• 英文别名: 4-[[1-[4-[Bis(2-chloroethyl)amino]anilino]-1-oxopropan-2-yl]amino]-3,5-dinitrobenzoic acid
• CAS: 220903-73-1
• 化学式: C₂₀H₂₁Cl₂N₅O₇
• 分子量: 514.322
• InChiKey: YORRHULWAXSIBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  173
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N,N-二甲基乙二胺 、 N-<4-phenyl>-2-<(4-carboxy-2,6-dinitrophenyl)amino>propanamide 在 N,N'-羰基二咪唑 作用下， 生成 4-[[1-[4-[bis(2-chloroethyl)amino]anilino]-1-oxopropan-2-yl]amino]-N-[2-(dimethylamino)ethyl]-3,5-dinitrobenzamide
  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
• 作为产物：
  描述：

  N,N-bis(2-chloroethyl)benzene-1,4-diamine hydrochloride 在 氰基磷酸二乙酯 、 二异丙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 15.5h， 生成 N-<4-phenyl>-2-<(4-carboxy-2,6-dinitrophenyl)amino>propanamide
  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

文献信息

• <i>N</i>-Substituted 2-(2,6-Dinitrophenylamino)propanamides:  Novel Prodrugs That Release a Primary Amine via Nitroreduction and Intramolecular Cyclization
  作者：Bridget M. Sykes、Graham J. Atwell、Alison Hogg、William R. Wilson、Charmian J. O'Connor、William A. Denny

  DOI：10.1021/jm960783s

  日期：1999.2.1

  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.