N-{7-benzyl-4-methyl-5-[(3-methoxyphenyl)ethynyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl}-2,2-dimethylpropanamide | 945910-46-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: N-{7-benzyl-4-methyl-5-[(3-methoxyphenyl)ethynyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl}-2,2-dimethylpropanamide
• 英文别名: N-[7-benzyl-5-[2-(3-methoxyphenyl)ethynyl]-4-methylpyrrolo[2,3-d]pyrimidin-2-yl]-2,2-dimethylpropanamide
• CAS: 945910-46-3
• 化学式: C₂₈H₂₈N₄O₂
• 分子量: 452.556
• InChiKey: HZDNEGBIAUKJKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  69
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-{7-benzyl-4-methyl-5-[(3-methoxyphenyl)ethynyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl}-2,2-dimethylpropanamide 在 palladium on activated charcoal sodium hydroxide 、 氨 、 氢气 、 sodium 作用下， 以 甲醇 、 二氯甲烷 为溶剂， -78.0~80.0 ℃ 、344.75 kPa 条件下， 反应 28.5h， 生成 5-[2-(3-methoxyphenyl)ethyl]-4-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-amine
  参考文献：
  名称：

  Discovery of Novel Antitumor Antimitotic Agents That Also Reverse Tumor Resistance

  摘要：

  We have discovered a novel series of 7-benzyl-4-methyl-5-[(2-substituted phenyl)ethyl]-7H-pyrrolo[2,3-d]-pyrimidin-2-amines, which possess antimitotic and antitumor activities against antimitotic-sensitive as well as resistant tumor cells. These agents bind to a site on tubulin that is distinct from the colchicine, vinca alkaloid, and paclitaxel binding sites and some, in addition to their antitumor activity, remarkably also reverse tumor resistance to antimitotic agents mediated via the P-glycoprotein efflux pump. The compounds were synthesized from N-(7-benzyl-5-ethynyl-4-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropanamide 11 or the corresponding 5-iodo analog 14 via Sonogashira couplings with appropriate iodobenzenes or phenylacetylene followed by reduction and deprotection to afford the target analogs. Sodium and liquid NH3 afforded the debenzylated analogs. The most potent analog 1 was one to three digit nanomolar against the growth of both sensitive and resistant tumor cells in culture. Compounds of this series are promising novel antimitotic agents that have the potential for treating both sensitive and resistant tumors.

  DOI：

  10.1021/jm070194u
• 作为产物：
  描述：

  3-碘苯甲醚 、 2-pivaloylamino-4-methyl-5-ethynyl-7-(N-benzyl)pyrrolo[2,3-d]pyrimidine 在 copper(l) iodide 、 四(三苯基膦)钯 三乙胺 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 3.5h， 以62%的产率得到N-{7-benzyl-4-methyl-5-[(3-methoxyphenyl)ethynyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl}-2,2-dimethylpropanamide
  参考文献：
  名称：

  Discovery of Novel Antitumor Antimitotic Agents That Also Reverse Tumor Resistance

  摘要：

  We have discovered a novel series of 7-benzyl-4-methyl-5-[(2-substituted phenyl)ethyl]-7H-pyrrolo[2,3-d]-pyrimidin-2-amines, which possess antimitotic and antitumor activities against antimitotic-sensitive as well as resistant tumor cells. These agents bind to a site on tubulin that is distinct from the colchicine, vinca alkaloid, and paclitaxel binding sites and some, in addition to their antitumor activity, remarkably also reverse tumor resistance to antimitotic agents mediated via the P-glycoprotein efflux pump. The compounds were synthesized from N-(7-benzyl-5-ethynyl-4-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropanamide 11 or the corresponding 5-iodo analog 14 via Sonogashira couplings with appropriate iodobenzenes or phenylacetylene followed by reduction and deprotection to afford the target analogs. Sodium and liquid NH3 afforded the debenzylated analogs. The most potent analog 1 was one to three digit nanomolar against the growth of both sensitive and resistant tumor cells in culture. Compounds of this series are promising novel antimitotic agents that have the potential for treating both sensitive and resistant tumors.

  DOI：

  10.1021/jm070194u

文献信息

• Discovery of Novel Antitumor Antimitotic Agents That Also Reverse Tumor Resistance
  作者：Aleem Gangjee、Jianming Yu、Jean E. Copper、Charles D. Smith

  DOI：10.1021/jm070194u

  日期：2007.7.1

  We have discovered a novel series of 7-benzyl-4-methyl-5-[(2-substituted phenyl)ethyl]-7H-pyrrolo[2,3-d]-pyrimidin-2-amines, which possess antimitotic and antitumor activities against antimitotic-sensitive as well as resistant tumor cells. These agents bind to a site on tubulin that is distinct from the colchicine, vinca alkaloid, and paclitaxel binding sites and some, in addition to their antitumor activity, remarkably also reverse tumor resistance to antimitotic agents mediated via the P-glycoprotein efflux pump. The compounds were synthesized from N-(7-benzyl-5-ethynyl-4-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropanamide 11 or the corresponding 5-iodo analog 14 via Sonogashira couplings with appropriate iodobenzenes or phenylacetylene followed by reduction and deprotection to afford the target analogs. Sodium and liquid NH3 afforded the debenzylated analogs. The most potent analog 1 was one to three digit nanomolar against the growth of both sensitive and resistant tumor cells in culture. Compounds of this series are promising novel antimitotic agents that have the potential for treating both sensitive and resistant tumors.