8-hydrazino-1,3-dimethyl-7-(1-ethoxycarbonylbenzyl)-3,7-dihydropurine-2,6-dione | 1400287-94-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 8-hydrazino-1,3-dimethyl-7-(1-ethoxycarbonylbenzyl)-3,7-dihydropurine-2,6-dione
• CAS: 1400287-94-6
• 化学式: C₁₇H₂₀N₆O₄
• 分子量: 372.384
• InChiKey: MIKQGVYYZXMIOP-UHFFFAOYSA-N

物化性质

• 熔点：
  254-255 °C
• 沸点：
  531.3±60.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.06
• 重原子数：
  27.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  126.17
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  8-hydrazino-1,3-dimethyl-7-(1-ethoxycarbonylbenzyl)-3,7-dihydropurine-2,6-dione 在 magnesium sulfate 、 lithium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 2-[[8-[(2Z)-2-[(3-ethoxy-4-hydroxyphenyl)methylidene]hydrazinyl]-1,3-dimethyl-2,6-dioxopurin-7-yl]methyl]benzoic acid
  参考文献：
  名称：

  Design and synthesis of EGFR dimerization inhibitors and evaluation of their potential in the treatment of psoriasis

  摘要：

  Hit compounds from in silico screening for inhibitors of the EGFR dimerization process were evaluated for their anti-proliferative (CCD-1106 keratinocytes) and anti-oxidant (TBA assay) activity and their effect on EGFR dimerization (BS3 chemical crosslinking assay). 7-Benzyl-8-{N'-[1-( 3-ethoxy-4-hydroxyphenyl)meth-(Z)-ylidene]hydrazino}-1,3-dimethylxanthine 2a (127 mu M) leads to 37% inhibition of p-EGFR dimerization in the CCD-1106 cell line and also inhibits phosphorylation of proteins in the MAPK/ERK pathway, ERK 1/2 and p-38. Based on this initial data, 2a was selected for further study and was evaluated for its anti-proliferative activity in a range of keratinocyte (CCD-1106, HaCaT and NHEK) and monocyte (ThP1 and U937) cell lines. Xanthine 2a is pro-apoptotic in HaCaT keratinocytes, as shown by electron microscopy, caspase 3/7, and annexin V-FITC/PI flow cytometric assays. It is significantly less cytotoxic than the established antipsoriatic agent dithranol 14, as determined by MTT and LDH release assays, and thus has potential as a lead compound for the treatment of psoriasis. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.048
• 作为产物：
  描述：

  8-氯茶碱 在 potassium carbonate 、 一水合肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 8-hydrazino-1,3-dimethyl-7-(1-ethoxycarbonylbenzyl)-3,7-dihydropurine-2,6-dione
  参考文献：
  名称：

  Design and synthesis of EGFR dimerization inhibitors and evaluation of their potential in the treatment of psoriasis

  摘要：

  Hit compounds from in silico screening for inhibitors of the EGFR dimerization process were evaluated for their anti-proliferative (CCD-1106 keratinocytes) and anti-oxidant (TBA assay) activity and their effect on EGFR dimerization (BS3 chemical crosslinking assay). 7-Benzyl-8-{N'-[1-( 3-ethoxy-4-hydroxyphenyl)meth-(Z)-ylidene]hydrazino}-1,3-dimethylxanthine 2a (127 mu M) leads to 37% inhibition of p-EGFR dimerization in the CCD-1106 cell line and also inhibits phosphorylation of proteins in the MAPK/ERK pathway, ERK 1/2 and p-38. Based on this initial data, 2a was selected for further study and was evaluated for its anti-proliferative activity in a range of keratinocyte (CCD-1106, HaCaT and NHEK) and monocyte (ThP1 and U937) cell lines. Xanthine 2a is pro-apoptotic in HaCaT keratinocytes, as shown by electron microscopy, caspase 3/7, and annexin V-FITC/PI flow cytometric assays. It is significantly less cytotoxic than the established antipsoriatic agent dithranol 14, as determined by MTT and LDH release assays, and thus has potential as a lead compound for the treatment of psoriasis. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.048