7-[(3,4-Dimethoxyphenyl)methyl]-4-methyl-5-[2-(3,4,5-trimethoxyphenyl)ethyl]pyrrolo[2,3-d]pyrimidin-2-amine | 1424430-55-6

• 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: 7-[(3,4-Dimethoxyphenyl)methyl]-4-methyl-5-[2-(3,4,5-trimethoxyphenyl)ethyl]pyrrolo[2,3-d]pyrimidin-2-amine
• 英文别名: 7-[(3,4-dimethoxyphenyl)methyl]-4-methyl-5-[2-(3,4,5-trimethoxyphenyl)ethyl]pyrrolo[2,3-d]pyrimidin-2-amine
• CAS: 1424430-55-6
• 化学式: C₂₇H₃₂N₄O₅
• 分子量: 492.575
• InChiKey: VBWGMYYHLARHEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  7-(3,4-dimethoxybenzyl)-4-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-amine 在 4-二甲氨基吡啶 、 N-碘代丁二酰亚胺 、 copper(l) iodide 、 四(三苯基膦)钯 、 5%-palladium/activated carbon 、 氢气 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0~100.0 ℃ 、344.75 kPa 条件下， 反应 24.17h， 生成 7-[(3,4-Dimethoxyphenyl)methyl]-4-methyl-5-[2-(3,4,5-trimethoxyphenyl)ethyl]pyrrolo[2,3-d]pyrimidin-2-amine
  参考文献：
  名称：

  Synthesis of 5,7-disubstituted-4-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-amines as microtubule inhibitors

  摘要：

  Compounds 1-4 were previously reported as potent antimitotic and antitumor agents with Pgp modulatory effects. Compounds 5-18 have been synthesized in an attempt to optimize the various activities of 1-4. Compounds 5-10 explored the influence of methoxy substitutions on the 7-benzyl moiety in 1, while 11-18 investigated the influence of incorporation of a sulfur linker at C5 compared to 1-3. Compounds 5-10 demonstrated potent single-digit micromolar tumor cell cytotoxicity, Pgp modulation and microtubule inhibition. Compound 7 of this series was the most potent and showed GI(50) values in the nanomolar range against several human tumor cell lines in the standard NCI preclinical in vitro screen. Antitumor activity and Pgp modulatory effects were found to decrease for the 5-phenylthio compounds 11-14 compared to their 5-phenylethyl analogs 2-4 and the standard compound Taxol. Incorporation of methoxy substitutions on the 7-benzyl moiety improved antitumor activity for the 5-phenylthio compounds 16 and 17. Compounds 16 and 17 demonstrated single to two-digit micromolar inhibition of tumor cells. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.029

文献信息

• Synthesis of 5,7-disubstituted-4-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-amines as microtubule inhibitors
  作者：Aleem Gangjee、Sonali Kurup、Charles D. Smith

  DOI：10.1016/j.bmc.2012.12.029

  日期：2013.3

  Compounds 1-4 were previously reported as potent antimitotic and antitumor agents with Pgp modulatory effects. Compounds 5-18 have been synthesized in an attempt to optimize the various activities of 1-4. Compounds 5-10 explored the influence of methoxy substitutions on the 7-benzyl moiety in 1, while 11-18 investigated the influence of incorporation of a sulfur linker at C5 compared to 1-3. Compounds 5-10 demonstrated potent single-digit micromolar tumor cell cytotoxicity, Pgp modulation and microtubule inhibition. Compound 7 of this series was the most potent and showed GI(50) values in the nanomolar range against several human tumor cell lines in the standard NCI preclinical in vitro screen. Antitumor activity and Pgp modulatory effects were found to decrease for the 5-phenylthio compounds 11-14 compared to their 5-phenylethyl analogs 2-4 and the standard compound Taxol. Incorporation of methoxy substitutions on the 7-benzyl moiety improved antitumor activity for the 5-phenylthio compounds 16 and 17. Compounds 16 and 17 demonstrated single to two-digit micromolar inhibition of tumor cells. (C) 2013 Elsevier Ltd. All rights reserved.