(E)-2-(2-(3,5-dimethoxybenzylidene)hydrazinyl)-4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine 6,6-dioxide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃吡啶类
• 英文名称: (E)-2-(2-(3,5-dimethoxybenzylidene)hydrazinyl)-4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine 6,6-dioxide
• 英文别名: N-[(E)-(3,5-dimethoxyphenyl)methylideneamino]-4-morpholin-4-yl-6,6-dioxo-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-2-amine
• 化学式: C₂₀H₂₅N₅O₅S
• 分子量: 447.515
• InChiKey: OZYPZQGHXVIKDG-CIAFOILYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,4-二氯-7,8-二氢-5H-噻喃并[4,3-d]嘧啶 在 sodium tungstate (VI) dihydrate 、 双氧水 、 一水合肼 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 5.5h， 生成 (E)-2-(2-(3,5-dimethoxybenzylidene)hydrazinyl)-4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine 6,6-dioxide
  参考文献：
  名称：

  Design, synthesis, anticancer activity and docking studies of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives as mTOR inhibitors

  摘要：

  A series of 7,8-dihydro-5H-thiopyrano[4,3-d] pyrimidine derivatives (7a-q, 10a-q) were designed, synthesized and their chemical structures were confirmed by H-1 NMR, C-13 NMR, MS and HRMS spectrum. All the compounds were evaluated for the inhibitory activity against mTOR kinase at 10 mu M level. Five selected compounds (7b, 7e, 7h, 10b and 10e) were further evaluated for the inhibitory activity against PI3K alpha at 10 mu M level, and the IC50 values against mTOR kinase and two cancer cell lines. Twelve of the target compounds exhibited moderate antitumor activities. The most promising compound 7e showed strong antitumor activities against mTOR kinase, H460 and PC-3 cell lines with IC50 values of 0.80 +/- 0.15 mu M, 7.43 +/- 1.45 mu M and 11.90 +/- 0.94 mu M, which were 1.28 to 1.71-fold more active than BMCL-200908069-1 (1.37 +/- 0.07 mu M, 9.52 +/- 0.29 mu M, 16.27 +/- 0.54 mu M), respectively. Structure-activity relationships (SARs) and docking studies indicated that the thiopyrano[4,3-d] pyrimidine scaffolds exerted little effect on antitumor activities of target compounds. Substitutions of aryl group at C-4 position had a significant impact on the antitumor activities, and 4-OH substitution produced the best potency. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.11.003

文献信息

• Design, synthesis, anticancer activity and docking studies of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives as mTOR inhibitors
  作者：Wufu Zhu、Chengyu Sun、Shan Xu、Chunjiang Wu、Jielian Wu、Mengze Xu、He Zhao、Le Chen、Weipeng Zeng、Pengwu Zheng

  DOI：10.1016/j.bmc.2014.11.003

  日期：2014.12

  A series of 7,8-dihydro-5H-thiopyrano[4,3-d] pyrimidine derivatives (7a-q, 10a-q) were designed, synthesized and their chemical structures were confirmed by H-1 NMR, C-13 NMR, MS and HRMS spectrum. All the compounds were evaluated for the inhibitory activity against mTOR kinase at 10 mu M level. Five selected compounds (7b, 7e, 7h, 10b and 10e) were further evaluated for the inhibitory activity against PI3K alpha at 10 mu M level, and the IC50 values against mTOR kinase and two cancer cell lines. Twelve of the target compounds exhibited moderate antitumor activities. The most promising compound 7e showed strong antitumor activities against mTOR kinase, H460 and PC-3 cell lines with IC50 values of 0.80 +/- 0.15 mu M, 7.43 +/- 1.45 mu M and 11.90 +/- 0.94 mu M, which were 1.28 to 1.71-fold more active than BMCL-200908069-1 (1.37 +/- 0.07 mu M, 9.52 +/- 0.29 mu M, 16.27 +/- 0.54 mu M), respectively. Structure-activity relationships (SARs) and docking studies indicated that the thiopyrano[4,3-d] pyrimidine scaffolds exerted little effect on antitumor activities of target compounds. Substitutions of aryl group at C-4 position had a significant impact on the antitumor activities, and 4-OH substitution produced the best potency. (C) 2014 Elsevier Ltd. All rights reserved.