6-[2-Hydroxy-3-(4-phenylpiperazin-1-yl)propoxy]-4-methylchromen-2-one | 1082467-61-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 6-[2-Hydroxy-3-(4-phenylpiperazin-1-yl)propoxy]-4-methylchromen-2-one
• CAS: 1082467-61-5
• 化学式: C₂₃H₂₆N₂O₄
• 分子量: 394.47
• InChiKey: PRAZRRNYXLNYFD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  62.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-苯基哌嗪 、 4-methyl-6-[(oxiran-2-yl)methoxy]-2H-1-benzopyran-2-one 以 乙醇 为溶剂， 反应 1.5h， 以93%的产率得到6-[2-Hydroxy-3-(4-phenylpiperazin-1-yl)propoxy]-4-methylchromen-2-one
  参考文献：
  名称：

  Design, synthesis, and docking studies of novel benzopyrone derivatives as H1-antihistaminic agents

  摘要：

  Two new series of 2H-1-benzopyran-2-one derivatives substituted at C-6 and/or C-7 with propanolamines, and/or piperazine propanol derivatives have been synthesized and assayed for the H-1-histamine antagonist. Twelve of the 20 newly synthesized 4-substituted benzopyrones have shown potent antihistaminic H-1 activity. In addition, molecular modeling and docking of the tested compounds into high affinity histamine binding protein (HBP) and histamine N-methyltranseferase (HNMT) active site in complex with its bound inhibitor (diphenhydramine) was performed in order to predict the affinity and orientation of these compounds at the active sites. The ICM score values show good agreement with predicted binding affinities obtained by molecular docking studies as verified by pharmacological screening. The results showed similar orientation of the target compounds at HBP, and HNMT active sites compared with reported histamine H1 antagonist. Also, it was concluded that in order for the compounds to be active, they must bind with both active sites of HNMT enzyme (two pockets) to inhibit it. Compounds 8c, 8i, 11g, 11i, and 11k; observe the maximum activities. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.08.039

文献信息

• Design, synthesis, and docking studies of novel benzopyrone derivatives as H1-antihistaminic agents
  作者：Nahla. A. Farag、Shadia. R. Mohamed、Gamal A.H. Soliman

  DOI：10.1016/j.bmc.2008.08.039

  日期：2008.10

  Two new series of 2H-1-benzopyran-2-one derivatives substituted at C-6 and/or C-7 with propanolamines, and/or piperazine propanol derivatives have been synthesized and assayed for the H-1-histamine antagonist. Twelve of the 20 newly synthesized 4-substituted benzopyrones have shown potent antihistaminic H-1 activity. In addition, molecular modeling and docking of the tested compounds into high affinity histamine binding protein (HBP) and histamine N-methyltranseferase (HNMT) active site in complex with its bound inhibitor (diphenhydramine) was performed in order to predict the affinity and orientation of these compounds at the active sites. The ICM score values show good agreement with predicted binding affinities obtained by molecular docking studies as verified by pharmacological screening. The results showed similar orientation of the target compounds at HBP, and HNMT active sites compared with reported histamine H1 antagonist. Also, it was concluded that in order for the compounds to be active, they must bind with both active sites of HNMT enzyme (two pockets) to inhibit it. Compounds 8c, 8i, 11g, 11i, and 11k; observe the maximum activities. (C) 2008 Elsevier Ltd. All rights reserved.