pteroic acid | 137465-05-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: pteroic acid
• 英文别名: 4-(1,3-diamino-7,8,9,10-tetrahydropyrimido[4,5-c]isoquinolin-8-yl)benzoic acid
• CAS: 137465-05-5
• 化学式: C₁₈H₁₇N₅O₂
• 分子量: 335.365
• InChiKey: LDVHXOPORPWXQA-UHFFFAOYSA-N

物化性质

• 沸点：
  678.6±65.0 °C(Predicted)
• 密度：
  1.449±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.16
• 重原子数：
  25.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  128.01
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  pteroic acid 在 sodium hydroxide 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 乙二醇甲醚 为溶剂， 反应 27.5h， 生成 (2S)-2-[[4-(1,3-二氨基-7,8,9,10-四氢嘧啶并[6,5-c]异喹啉-8-基)苯甲酰基]氨基]戊烷二酸
  参考文献：
  名称：

  Synthesis and antifolate properties of 5,10-ethano-5,10-dideazaaminopterin

  摘要：

  2-Carbomethoxy-4-(p-carbomethoxyphenyl)cyclohexanone was prepared in a four-step process and thermally condensed with 2,4,6-triaminopyrimidine to afford methyl 2,4-diamino-4-deoxy-7-hydroxy-5,10-ethano-5,10-dideazapteroate. Reduction of the 7-oxo function with borane gave the 7,8-dihydro pterin which was subsequently oxidized to the fully aromatic pteroate ester with dicyanodichlorobenzoquinone. Saponification of the benzoate ester, coupling with diethyl glutamate and final ester hydrolysis afforded the title compound. This novel deazaaminopterin analogue was approximately as potent as methotrexate in vitro in terms of DHFR and L1210 cell growth inhibition. There are indications of diastereomeric differences in the enzyme inhibition measurements. A significant transport advantage over MTX for influx into L1210 cells was observed. The compound was active against the E 0771 murine mammary solid tumor, but further investigation with individual diastereomers is required to define the ED50.

  DOI：

  10.1021/jm00080a017
• 作为产物：
  描述：

  methyl 4-(1,3-diamino-5,6,7,8,9,10-hexahydropyrimido[4,5-c]isoquinolin-8-yl)benzoate 在 sodium hydroxide 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 乙二醇甲醚 、 溶剂黄146 为溶剂， 反应 36.0h， 生成 pteroic acid
  参考文献：
  名称：

  Synthesis and antifolate properties of 5,10-ethano-5,10-dideazaaminopterin

  摘要：

  2-Carbomethoxy-4-(p-carbomethoxyphenyl)cyclohexanone was prepared in a four-step process and thermally condensed with 2,4,6-triaminopyrimidine to afford methyl 2,4-diamino-4-deoxy-7-hydroxy-5,10-ethano-5,10-dideazapteroate. Reduction of the 7-oxo function with borane gave the 7,8-dihydro pterin which was subsequently oxidized to the fully aromatic pteroate ester with dicyanodichlorobenzoquinone. Saponification of the benzoate ester, coupling with diethyl glutamate and final ester hydrolysis afforded the title compound. This novel deazaaminopterin analogue was approximately as potent as methotrexate in vitro in terms of DHFR and L1210 cell growth inhibition. There are indications of diastereomeric differences in the enzyme inhibition measurements. A significant transport advantage over MTX for influx into L1210 cells was observed. The compound was active against the E 0771 murine mammary solid tumor, but further investigation with individual diastereomers is required to define the ED50.

  DOI：

  10.1021/jm00080a017