diethyl N-(4-nitrobenzoyl)-L-aspartate | 27128-94-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: diethyl N-(4-nitrobenzoyl)-L-aspartate
• 英文别名: Diaethyl-N-(p-nitrobenzoyl)-L-asparginat；diethyl (2S)-2-[(4-nitrobenzoyl)amino]butanedioate
• CAS: 27128-94-5
• 化学式: C₁₅H₁₈N₂O₇
• 分子量: 338.317
• InChiKey: CFUWWCWIAUTJHP-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diethyl N-(4-nitrobenzoyl)-L-aspartate 在 palladium on activated charcoal 2,6-二甲基吡啶 、 氢气 、 calcium carbonate 作用下， 以 乙醇 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 144.0h， 生成 diethyl N-<4-prop-2-ynylamino>benzoyl>-L-aspartate
  参考文献：
  名称：

  Quinazoline antifolates inhibiting thymidylate synthase. Variation of the amino acid

  摘要：

  Five new analogues (1c-g) of the antifolate N10-propargyl-5,8-dideazafolic acid (1a) are described in which the benzoyl-L-glutamate moiety was replaced by benzoic acid (desglutamyl-N10-propargyl-5,8-dideazafolic acid), benzoyl-L-aspartate, 4-phenylbutyrate, benzoylglycine, and benzoyl-L-alanine. The esters of the appropriate 4-aminophenyl (benzoyl) starting materials were sequentially alkylated upon nitrogen, first with a propargyl halide and then with 2-amino-6-(bromomethyl)-4-hydroxyquinazoline hydrobromide. Saponification of the antifolate esters so produced gave the desired analogues. The new derivatives (1c-g) and also the known diethyl ester of 1a (1b) were tested for their inhibition of purified L1210 thymidylate synthase (TS) and for their inhibition of the growth of L1210 cells in culture. The TS inhibition of the analogues 1b-g was estimated by calculating the inverse relative potency, defined as the ratio IC50(compound)/IC50(1a). The results obtained were as follows: greater than 62, 84, 9, 333, 21, and 5, respectively. All were thus less inhibitory than 1a. None of the compounds improved upon 1a in inhibiting the growth of L1210 cells in culture.

  DOI：

  10.1021/jm00156a033
• 作为产物：
  描述：

  4-硝基苯甲酰氯 、 diethyl L-aspartate hydrochloride 在 吡啶 作用下， 以 甲苯 为溶剂， 以53%的产率得到diethyl N-(4-nitrobenzoyl)-L-aspartate
  参考文献：
  名称：

  Quinazoline antifolates inhibiting thymidylate synthase. Variation of the amino acid

  摘要：

  Five new analogues (1c-g) of the antifolate N10-propargyl-5,8-dideazafolic acid (1a) are described in which the benzoyl-L-glutamate moiety was replaced by benzoic acid (desglutamyl-N10-propargyl-5,8-dideazafolic acid), benzoyl-L-aspartate, 4-phenylbutyrate, benzoylglycine, and benzoyl-L-alanine. The esters of the appropriate 4-aminophenyl (benzoyl) starting materials were sequentially alkylated upon nitrogen, first with a propargyl halide and then with 2-amino-6-(bromomethyl)-4-hydroxyquinazoline hydrobromide. Saponification of the antifolate esters so produced gave the desired analogues. The new derivatives (1c-g) and also the known diethyl ester of 1a (1b) were tested for their inhibition of purified L1210 thymidylate synthase (TS) and for their inhibition of the growth of L1210 cells in culture. The TS inhibition of the analogues 1b-g was estimated by calculating the inverse relative potency, defined as the ratio IC50(compound)/IC50(1a). The results obtained were as follows: greater than 62, 84, 9, 333, 21, and 5, respectively. All were thus less inhibitory than 1a. None of the compounds improved upon 1a in inhibiting the growth of L1210 cells in culture.

  DOI：

  10.1021/jm00156a033

文献信息

• Quinazoline analogues of folic acid
  作者：J. Davoll、A. M. Johnson

  DOI：10.1039/j39700000997

  日期：——

  Analogues of folic acid having the pteridine ring replaced by quinazoline have been prepared by reductive condensation of appropriately substituted quinazoline-6-carbaldehydes and -carbonitriles with diesters of N-(p-aminobenzoyl) amino-acids, followed by hydrolysis.

  通过将适当取代的喹唑啉-6-甲醛和-腈与N-（对氨基苯甲酰基）氨基酸的二酯进行还原性缩合反应，制备了具有被喹唑啉取代的蝶啶环的叶酸的类似物。
• Ligands for metal affinity chromatography
  申请人：——

  公开号：US20020019496A1

  公开（公告）日：2002-02-14

  The invention provides a metal chelate resin that comprises repeating units having the structure: 1 where M is a metal ion in an oxidation state capable of forming a complex with a tetradentate ligand having an overall coordination number of at least 6, R1, R2, R3, R4 and R5 are each hydrogen, halogen, straight-chain or branched alkyl, or alkenyl having 1 to 4 carbon atoms, halogenoalkyl having 1 or 2 carbon atoms and 1 to 5 fluorine, chlorine and/or bromine atoms, straight-chain or branched alkoxyalkyl having 1 to 3 carbon atoms in the alkoxy moiety and 1 to 3 carbon atoms in the alkyl moiety, alkylcarbonyl having 1 to 4 carbon atoms in the straight-chain or branched alkyl moiety, phenyl, or phenylcarbonyl, it being possible for each of the above mentioned phenyl radicals to be mono- to tri-substituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, alkyl having 1 or 2 carbon atoms, alkoxy having 1 or 2 carbon atoms, alkylthio having 1 or 2 carbon atoms, halogenoalkyl having 1 or 2 carbon atoms and 1 to 5 fluorine, chlorine and/or bromine atoms, halogenoalkoxy having 1 or 2 carbon atoms and 1 to 5 fluorine, chlorine and/or bromine atoms, halogenoalkylthio having 1 or 2 carbon atoms and 1 to 5 fluorine, chlorine and/or bromine atoms, provided that if R2, R3, R4 and R5 are all hydrogen R1 may not be hydrogen, R6 is a linking arm connecting the nitrogen atom of the ligand with R7 where R7 is a functional linking group through which the R6 linking arm is connected to R8 and R8 is an insoluble immobilization matix.

  本发明提供了一种金属螯合树脂，它由具有以下结构的重复单元组成： 1 其中 M 是处于氧化态的金属离子，能与总配位数至少为 6 的四价配体形成络合物，R1、R2、R3、R4 和 R5 分别是氢、卤素、直链或支链烷基或具有 1 至 4 个碳原子的烯基、具有 1 或 2 个碳原子和 1 至 5 个氟、氯和/或溴原子的卤代烷基、在直链或支链烷基中具有 1 至 3 个碳原子的直链或支链烷氧基烷基和具有 1 至 3 个碳原子的烷基、在直链或支链烷基中具有 1 至 4 个碳原子的烷基羰基、苯基或苯基羰基，上述每个苯基都可以被由氟组成的组中相同或不同的取代基单取代或三取代、氯、溴、氰基、硝基、具有 1 或 2 个碳原子的烷基、具有 1 或 2 个碳原子的烷氧基、具有 1 或 2 个碳原子的烷硫基、具有 1 或 2 个碳原子和 1 至 5 个氟、氯和/或溴原子的卤代烷基、具有 1 或 2 个碳原子和 1 至 5 个氟、氯和/或溴原子的卤代烷氧基、具有 1 或 2 个碳原子和 1 至 5 个氟、氯和/或溴原子的卤代烷基硫，条件是如果 R2、R3、R4 和 R5 都是氢，R1 可能不是氢，R6 是连接配体的氮原子与 R7 的连接臂，其中 R7 是官能连接基团，R6 连接臂通过该官能连接基团与 R8 连接，R8 是不溶性固定基团。