N-[7-(3,4,5-trimethoxybenzyl)-4-methyl-5-[(2-methoxyphenyl)sulfanyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl]-2,2-dimethylpropanamide | 1424430-95-4

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: N-[7-(3,4,5-trimethoxybenzyl)-4-methyl-5-[(2-methoxyphenyl)sulfanyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl]-2,2-dimethylpropanamide
• CAS: 1424430-95-4
• 化学式: C₂₉H₃₄N₄O₅S
• 分子量: 550.679
• InChiKey: QZNPMKZQPSTWAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.96
• 重原子数：
  39.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  96.73
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  N-[7-(3,4,5-trimethoxybenzyl)-4-methyl-5-[(2-methoxyphenyl)sulfanyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl]-2,2-dimethylpropanamide 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 12.0h， 以56%的产率得到5-(2-Methoxyphenyl)sulfanyl-4-methyl-7-[(3,4,5-trimethoxyphenyl)methyl]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
• 作为产物：
  描述：

  三甲基乙酰氯 在 4-二甲氨基吡啶 、 N-碘代丁二酰亚胺 、 copper(l) iodide 、 potassium carbonate 、 三乙胺 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 N-[7-(3,4,5-trimethoxybenzyl)-4-methyl-5-[(2-methoxyphenyl)sulfanyl]-7H-pyrrolo[2,3-d]pyrimidin-2-yl]-2,2-dimethylpropanamide
  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