dimethyl 2-cyano-4-[2-(4-methoxycarbonylphenyl)ethyl]pentanedioate | 357400-68-1

• 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: dimethyl 2-cyano-4-[2-(4-methoxycarbonylphenyl)ethyl]pentanedioate
• CAS: 357400-68-1
• 化学式: C₁₈H₂₁NO₆
• 分子量: 347.368
• InChiKey: QGYDUQOFXIUPGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  102.69
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  dimethyl 2-cyano-4-[2-(4-methoxycarbonylphenyl)ethyl]pentanedioate 在 盐酸 、 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 72.0h， 生成 4-[2-(2-amino-4-oxo-3,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidin-6-yl)ethyl]benzoic acid
  参考文献：
  名称：

  Selective Reduction of the 7-Oxo Group in Pyrido[2,3-d]pyrimidine-4,7-diones: A New Synthetic Approach to 5,10-Dideazatetrahydrofolic Acid (DDATHF)

  摘要：

  DOI：

  10.3987/com-99-s129
• 作为产物：
  描述：

  2-(溴甲基)丙烯酸甲酯 生成 dimethyl 2-cyano-4-[2-(4-methoxycarbonylphenyl)ethyl]pentanedioate
  参考文献：
  名称：

  Selective Reduction of the 7-Oxo Group in Pyrido[2,3-d]pyrimidine-4,7-diones: A New Synthetic Approach to 5,10-Dideazatetrahydrofolic Acid (DDATHF)

  摘要：

  DOI：

  10.3987/com-99-s129

文献信息

• Synthesis and Biological Activity of 7-Oxo Substituted Analogues of 5-Deaza-5,6,7,8-tetrahydrofolic Acid (5-DATHF) and 5,10-Dideaza-5,6,7,8-tetrahydrofolic Acid (DDATHF)
  作者：José I. Borrell、Jordi Teixidó、Josep Lluís Matallana、Blanca Martínez-Teipel、Carles Colominas、Marta Costa、Merche Balcells、Elisabeth Schuler、María José Castillo

  DOI：10.1021/jm990411u

  日期：2001.7.1

  We recently described the syntheses of 12a-c, 4-amino-7-oxo substituted analogues of 5-deaza-5,6,7,8-tetrahydrofolic acid (5-DATHF), and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), in six steps from commercially available p-substituted methyl benzoates in: 20-27% overall yields; Such analogues were tested in vitro against CCRF-CEM leukemia cells and showed that they are completely devoid of any activity, the IC50 being higher than 20 mug/mL for all cases. To clarify if the presence of the carbonyl group in position C7, the distinctive feature of our synthetic. methodology, is the reason for this lack of activity, we have now obtained the 7-oxo substituted analogues of 5-DATHF and DDATHF, 18a-c, in 10-30% overall yield. Testing of 18a-c in vitro against CCRF-CEM leukemia cells revealed that these compounds are totally inactive. A molecular modeling study of 18b inside the active site of the complex El coli GARTFase-5-DATHF-GAR pointed to an electronic repulsion between the atoms of the 7-ore group and the carbonyl group of Arg90 as a possible explanation for the inactivity of 18a-c.