(Z)-5-[(6′-methoxy-2-pyridinyl)methylene]-2,4-imidazolidinedione | 1256244-73-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (Z)-5-[(6′-methoxy-2-pyridinyl)methylene]-2,4-imidazolidinedione
• 英文别名: (Z)-5-((6-methoxypyridin-2-yl)methylene)imidazolidine-2,4-dione；(5Z)-5-[(6-methoxypyridin-2-yl)methylidene]imidazolidine-2,4-dione
• CAS: 1256244-73-1
• 化学式: C₁₀H₉N₃O₃
• 分子量: 219.2
• InChiKey: RJYWGZYDEPVECK-ALCCZGGFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  80.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  海因 、 6-甲氧基吡啶-2-甲醛 在 C.I.酸性橙108 作用下， 以 乙醇 、 水 为溶剂， 以58 %的产率得到(Z)-5-[(6′-methoxy-2-pyridinyl)methylene]-2,4-imidazolidinedione
  参考文献：
  名称：

  5-(杂芳基亚甲基)乙内酰脲作为糖原合酶激酶-3β抑制剂的合成与评价

  摘要：

  糖原合酶激酶 3 (GSK-3) 是一种丝氨酸/苏氨酸激酶，在多种蛋白质的磷酸化中发挥核心作用，通常会导致其失活。因此，GSK-3 被视为治疗靶点。据报道，GSK-3 有机小分子抑制剂的数量不断增加。已知苯亚甲基乙内酰脲表现出广泛的抑制活性，包括 GSK-3β。制备了 14 个 2-杂环取代的亚甲基乙内酰脲 (14、17-29) 家族，并评估了 25 μM 浓度下对 GSK-3β 的抑制作用。测定了其中五种化合物的 IC50 值；两种最好的抑制剂是 5-[(4'-氯-2-吡啶基)亚甲基]乙内酰脲 (IC50 = 2.14 ± 0.18 μM) 和 5-[(6'-溴-2-吡啶基)亚甲基]乙内酰脲 (IC50 = 3.39) ±0.16μM）。化合物与 GSK-3β (pdb 1q41) 的计算对接揭示了与 Val135 处主链形成氢键的位姿。 5-[(杂芳基)亚甲基]乙内酰脲不会强烈抑制其他金属酶，对

  DOI：

  10.3390/ph17050570

文献信息

• Phenylmethylene hydantoins as prostate cancer invasion and migration inhibitors. CoMFA approach and QSAR analysis
  作者：Mohammad A. Khanfar、Khalid A. El Sayed

  DOI：10.1016/j.ejmech.2010.08.066

  日期：2010.11

  Prostrate cancer constitutes the second leading cause of cancer deaths in men in United States. In the process of discovery of new antiproliferative and anti-metastatic agents against prostate cancer, marine-derived phenylmethylene hydantoin (PMH) derivatives were identified with activity level range between 50 and 200 mu M. 3D-QSAR CoMFA model was used in virtual screening of commercially available derivatives of PMH. PMH derivatives with manifold increase in anti-migratory and anti-invasive activities were discovered using wound-healing and Cultrex invasion assays. Benzene ring replacement with other heterocyclic rings did not significantly improve the methylene hydantoins activities. Multivariate analysis performed on the whole series of methylene hydantoins, which further supported the findings of CoMFA model. Predictive QSAR model with conventional r(2) and cross-validated coefficient (q(2)) values up to 0.982 and 0.803 were established. The molecular volume (MV) and the log P were identified as critical parameters for methylene hydatoins migration inhibitory activity. PMH is a novel anti-metastatic lead class with potential therapeutic activity against prostate cancer. (C) 2010 Elsevier Masson SAS. All rights reserved.
• 10.3390/ph17050570
  作者：Schneider, Nicholas O.、Gilreath, Kendra、Burkett, Daniel J.、St. Maurice, Martin、Donaldson, William A.

  DOI：10.3390/ph17050570

  日期：——

  Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase which plays a center role in the phosphorylation of a wide variety of proteins, generally leading to their inactivation. As such, GSK-3 is viewed as a therapeutic target. An ever-increasing number of small organic molecule inhibitors of GSK-3 have been reported. Phenylmethylene hydantoins are known to exhibit a wide range of inhibitory

  糖原合酶激酶 3 (GSK-3) 是一种丝氨酸/苏氨酸激酶，在多种蛋白质的磷酸化中发挥核心作用，通常会导致其失活。因此，GSK-3 被视为治疗靶点。据报道，GSK-3 有机小分子抑制剂的数量不断增加。已知苯亚甲基乙内酰脲表现出广泛的抑制活性，包括 GSK-3β。制备了 14 个 2-杂环取代的亚甲基乙内酰脲 (14、17-29) 家族，并评估了 25 μM 浓度下对 GSK-3β 的抑制作用。测定了其中五种化合物的 IC50 值；两种最好的抑制剂是 5-[(4'-氯-2-吡啶基)亚甲基]乙内酰脲 (IC50 = 2.14 ± 0.18 μM) 和 5-[(6'-溴-2-吡啶基)亚甲基]乙内酰脲 (IC50 = 3.39) ±0.16μM）。化合物与 GSK-3β (pdb 1q41) 的计算对接揭示了与 Val135 处主链形成氢键的位姿。 5-[(杂芳基)亚甲基]乙内酰脲不会强烈抑制其他金属酶，对