6-ethoxy-9-deazapurine

• 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: 6-ethoxy-9-deazapurine
• 英文别名: 4-Ethoxypyrrolo[3,2-d]pyrimidine；4-ethoxy-5H-pyrrolo[3,2-d]pyrimidine
• 化学式: C₈H₉N₃O
• 分子量: 163.179
• InChiKey: OGSKBVXRCWJDHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  50.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  三苯基膦氯金 、 6-ethoxy-9-deazapurine 在 sodium hydroxide 作用下， 以 水 、 丙酮 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Gold(I) Complexes of 9-Deazahypoxanthine as Selective Antitumor and Anti-Inflammatory Agents

  摘要：

  制备了包含 9-脱氮次黄嘌呤 (HLn) 和三苯基膦 (PPh3) 的 O 取代衍生物的金 (I) 混合配体配合物，其通式为 [Au(Ln)(PPh3)] (1–5)，并通过以下方法进行了彻底表征：元素分析、FT-IR 和多核 NMR 光谱、ESI+ 质谱、单晶 X 射线（HL5 和络合物 2）和 TG/DTA 分析。评估了复合物 1-5 对 9 种人类癌症系的体外抗肿瘤活性，即 MCF7（乳腺癌）、HOS（骨肉瘤）、A549（腺癌）、G361（黑色素瘤）、HeLa（宫颈癌）、A2780（卵巢癌） ）、A2780R（对顺铂耐药的卵巢癌）、22Rv1（前列腺癌）和 THP-1（单核细胞白血病），使用 LPS 激活的巨噬细胞模型进行体外抗炎活性，并通过 LPS 激活的巨噬细胞模型了解其体内抗水肿活性λ-角叉菜胶诱导的大鼠后足水肿模型。结果表明，复合物 1-5 对 MCF7、HOS、22Rv1、A2780 和 A2780R 表现出选择性体外细胞毒性，2 对 MCF7 (0.6 µM) 和 HOS (0.9 µM) 的 IC50 值为亚微摩尔。对人肝细胞 (HEP220) 原代培养物的体外细胞毒性筛选结果显示，与癌细胞相比，化合物对健康细胞的毒性低 30 倍。此外，复合物 1-5 通过与商业使用的抗关节炎药物 Auranofin 类似的方式显着影响促炎细胞因子 TNF-α 和 IL-1β 的分泌和表达。测试的复合物还显着影响大鼠足底内施用 λ-角叉菜胶多糖引起的水肿的速率和总体体积。基于这些有希望的结果，所提出的化合物有资格成为潜在的抗肿瘤和抗炎药物样化合物进行高级测试的可行候选者。

  DOI：

  10.1371/journal.pone.0109901

文献信息

• Synthesis, X-ray crystal structure and biological evaluation of zinc(II)-dichlorido complexes with 9-deazahypoxathine derivatives
  作者：Jana Gáliková、Jan Hošek、Zdeněk Trávníček

  DOI：10.1016/j.ica.2015.05.013

  日期：2015.8

  A series of mononuclear zinc(II)-dichlorido complexes of the general formula [Zn(L-n)(2)Cl-2]center dot Solv (1-5); n = 1-5, Solv = CH3CN for 1, 2CH(3)CN for 1b, 1/2H(2)O for complexes 2 and 4; containing 9-deazahypoxanthine derivatives (L-n, 6-(omega-alkyl) oxy-9-deazapurine derivatives) was prepared and thoroughly characterized (by elemental analysis, ESI+ mass spectrometry, FT-IR and multinuclear NMR spectroscopy, and TG/DTA analysis). Single crystal X-ray analysis of [Zn(L-1)(2)Cl-2]center dot 2CH(3)CN (1b) revealed a distorted tetrahedral geometry in the vicinity of the zinc(II) atom with two 6-ethoxy-9-deazapurine molecules (L-1) coordinated through the N3 atoms. The complexes were screened for their in vitro antitumor activity against three human cancer cell lines, PC3 and LNCaP (prostate carcinoma), and A2780 (ovarian carcinoma). Moreover, the ability of the complexes to modulate the secretion of interleukin IL-1 beta and matrix metalloproteinase MMP-2 activity on a lipopolysaccharide (LPS)-activated macrophage-like THP-1 cell model was evaluated. The results revealed that the zinc(II) complexes show no in vitro cytotoxicity within the range of 0.01-50 mu M on PC3, LNCaP and A2780 cell lines. The ability of the complexes to decrease the IL-1 beta production was not observed. On the other hand, these complexes were able to enhance the total amount of MMP-2 protein and significantly elevate the level of the active form of this protease. (C) 2015 Elsevier B.V. All rights reserved.
• Gold(I) Complexes of 9-Deazahypoxanthine as Selective Antitumor and Anti-Inflammatory Agents
  作者：Ján Vančo、Jana Gáliková、Jan Hošek、Zdeněk Dvořák、Lenka Paráková、Zdeněk Trávníček

  DOI：10.1371/journal.pone.0109901

  日期：——

  The gold(I) mixed-ligand complexes involving O-substituted derivatives of 9-deazahypoxanthine (HLn) and triphenylphosphine (PPh3) with the general formula [Au(Ln)(PPh3)] (1–5) were prepared and thoroughly characterized by elemental analysis, FT-IR and multinuclear NMR spectroscopy, ESI+ mass spectrometry, single crystal X-ray (HL5 and complex 2) and TG/DTA analyses. Complexes 1–5 were evaluated for their in vitro antitumor activity against nine human cancer lines, i.e. MCF7 (breast carcinoma), HOS (osteosarcoma), A549 (adenocarcinoma), G361 (melanoma), HeLa (cervical cancer), A2780 (ovarian carcinoma), A2780R (ovarian carcinoma resistant to cisplatin), 22Rv1 (prostate cancer) and THP-1 (monocytic leukaemia), for their in vitro anti-inflammatory activity using a model of LPS-activated macrophages, and for their in vivo antiedematous activity by λ-carrageenan-induced hind paw edema model on rats. The results showed that the complexes 1–5 exhibit selective in vitro cytotoxicity against MCF7, HOS, 22Rv1, A2780 and A2780R, with submicromolar IC50 values for 2 against the MCF7 (0.6 µM) and HOS (0.9 µM). The results of in vitro cytotoxicity screening on primary culture of human hepatocytes (HEP220) revealed up to 30-times lower toxicity of compounds against healthy cells as compared with cancer cells. Additionally, the complexes 1–5 significantly influence the secretion and expression of pro-inflammatory cytokines TNF-α and IL-1β by a similar manner as a commercially used anti-arthritic drug Auranofin. The tested complexes also significantly influence the rate and overall volume of the edema, caused by the intraplantar application of λ-carrageenan polysaccharide to rats. Based on these promising results, the presented compounds could qualify to become feasible candidates for advanced testing as potential antitumor and anti-inflammatory drug-like compounds.

  制备了包含 9-脱氮次黄嘌呤 (HLn) 和三苯基膦 (PPh3) 的 O 取代衍生物的金 (I) 混合配体配合物，其通式为 [Au(Ln)(PPh3)] (1–5)，并通过以下方法进行了彻底表征：元素分析、FT-IR 和多核 NMR 光谱、ESI+ 质谱、单晶 X 射线（HL5 和络合物 2）和 TG/DTA 分析。评估了复合物 1-5 对 9 种人类癌症系的体外抗肿瘤活性，即 MCF7（乳腺癌）、HOS（骨肉瘤）、A549（腺癌）、G361（黑色素瘤）、HeLa（宫颈癌）、A2780（卵巢癌） ）、A2780R（对顺铂耐药的卵巢癌）、22Rv1（前列腺癌）和 THP-1（单核细胞白血病），使用 LPS 激活的巨噬细胞模型进行体外抗炎活性，并通过 LPS 激活的巨噬细胞模型了解其体内抗水肿活性λ-角叉菜胶诱导的大鼠后足水肿模型。结果表明，复合物 1-5 对 MCF7、HOS、22Rv1、A2780 和 A2780R 表现出选择性体外细胞毒性，2 对 MCF7 (0.6 µM) 和 HOS (0.9 µM) 的 IC50 值为亚微摩尔。对人肝细胞 (HEP220) 原代培养物的体外细胞毒性筛选结果显示，与癌细胞相比，化合物对健康细胞的毒性低 30 倍。此外，复合物 1-5 通过与商业使用的抗关节炎药物 Auranofin 类似的方式显着影响促炎细胞因子 TNF-α 和 IL-1β 的分泌和表达。测试的复合物还显着影响大鼠足底内施用 λ-角叉菜胶多糖引起的水肿的速率和总体体积。基于这些有希望的结果，所提出的化合物有资格成为潜在的抗肿瘤和抗炎药物样化合物进行高级测试的可行候选者。