5,7-二羟基-4-甲基-3-(4-甲基哌嗪-1-基)-2H-色烯-2-酮 | 1209261-56-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 中文名称: 5,7-二羟基-4-甲基-3-(4-甲基哌嗪-1-基)-2H-色烯-2-酮
• 英文名称: 5,7-dihydroxy-4-methyl-3-(4-methylpiperazin-1-yl)-2H-chromen-2-one
• 英文别名: 5,7-dihydroxy-4-methyl-3-(4-methylpiperazin-1-yl)chromen-2-one
• CAS: 1209261-56-2
• 化学式: C₁₅H₁₈N₂O₄
• 分子量: 290.319
• InChiKey: WTGPVPWURYYDMO-UHFFFAOYSA-N

物化性质

• 熔点：
  208-210 °C
• 沸点：
  545.7±50.0 °C(Predicted)
• 密度：
  1.368±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  73.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5,7-二羟基-4-甲基-3-(4-甲基哌嗪-1-基)-2H-色烯-2-酮 在 吡啶 、 四丁基氟化铵 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 6.33h， 生成 5-butoxy-4-methyl-3-(4-methylpiperazin-1-yl)-2-oxo-2H-chromen-7-yl 4-methylbenzenesulfonate
  参考文献：
  名称：

  Coumarin derivatives protect against ischemic brain injury in rats

  摘要：

  Neuroprotection strategies are of great importance in the treatment of ischemic brain injury. Screening of our in-stock coumarin derivatives identified compound 1 as exhibiting neuroprotective activity. Subsequently, a structural optimization was carried out, which led to the discovery of the potent compound 20. This compound significantly attenuated the damage in a cell line derived from a pheochromocytoma of the rat adrenal medulla induced by oxygen glucose deprivation in vitro. Furthermore, compound 20 exhibited clear neuroprotection in middle cerebral artery occlusion rats by reducing infarct size and brain-water content, improving neurological function, and suppressing neuronal loss and neuropathological changes in the cortex and hippocampus. Pharmacokinetic evaluation indicated that compound 20 could penetrate the blood brain barrier of rats. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.015
• 作为产物：
  描述：

  N-甲基哌嗪 在 三氟化硼乙醚 、 potassium carbonate 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 18.0h， 生成 5,7-二羟基-4-甲基-3-(4-甲基哌嗪-1-基)-2H-色烯-2-酮
  参考文献：
  名称：

  香豆素衍生物的制备及其在防治脑部重大疾 病中的应用

  摘要：

  本发明公开一类新的香豆素化合物及其药学上可接受的盐，这类化合物的制备方法，含有这类化合物的药物组合物，这类化合物在制备预防或治疗脑疾病的药物中的应用，尤其是预防或治疗神经元损伤、神经炎症相关疾病，特别是预防或治疗帕金森氏症、痴呆、脑缺血、抑郁、脑卒中。

  公开号：

  CN103450134B

文献信息

• Discovery and Optimization of Novel 3-Piperazinylcoumarin Antagonist of Chemokine-like Factor 1 with Oral Antiasthma Activity in Mice
  作者：Gang Li、Dongmei Wang、Mingna Sun、Guangyan Li、Jinfeng Hu、Yun Zhang、Yuhe Yuan、Haijie Ji、Naihong Chen、Gang Liu

  DOI：10.1021/jm901652p

  日期：2010.2.25

  Chemokine-like factor 1 (CKLF1) is a novel functional cytokine that acts through receptor CC chemokine receptor 4 (CCR4). Activation of CCR4 by CKLF1 plays an important role in diseases such as asthma and multiple Sclerosis. This article describes a cell-based screening assay Using an FITC-labeled CCR4 agonist (CKLF1-C27), a CKLF1 peptide fragment. Screening of our in-stock small-molecule library identified a 3-piperazinylcoumarin analogue 1 (IC50 = 4.36 x 10(-6) M) that led to the discovery of orally active compound 41 (IC50 = 2.12 x 10(-8) M) through systematic optimization. Compound 41 blocked the calcium mobilization and chemotaxis induced by CKLF1-C27 and reduced the asthmatic pathologic changes in lung tissue of human CKLF1-transfected mice. Further studies indicated that compound 41 ameliorated pathological changes via inhibition of the NF-kappa B signal pathway.