(4-aminophenyl)-(2,4-dimethoxyphenyl)methanone

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4-aminophenyl)-(2,4-dimethoxyphenyl)methanone
• 化学式: C₁₅H₁₅NO₃
• mdl: MFCD01103034
• 分子量: 257.289
• InChiKey: CUWCMTXGFLYQKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.133
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-aminophenyl)-(2,4-dimethoxyphenyl)methanone 在 一水合肼 、 zinc(II) chloride 作用下， 生成
  参考文献：
  名称：

  DE2903709

  摘要：

  公开号：
• 作为产物：
  描述：

  对氨基苯甲酸 、 间苯二甲醚 在 氨 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 3.0h， 以89%的产率得到(4-aminophenyl)-(2,4-dimethoxyphenyl)methanone
  参考文献：
  名称：

  Discovery of new cholesteryl ester transfer protein inhibitors via ligand-based pharmacophore modeling and QSAR analysis followed by synthetic exploration

  摘要：

  Cholesteryl ester transfer protein (CETP) is involved in trafficking lipoprotein particles and neutral lipids between HDL and LDL and therefore is considered a valid target for treating dyslipidemic conditions and complications. Pharmacophore modeling and quantitative structure-activity relationship (QSAR) analysis were combined to explore the structural requirments for potent CETP inhibitors. Two pharmacophores emerged in the optimal QSAR equation (r(2) = 0.800, n = 96, F = 72.1. r(LOO)(2) = 0.775, r(PRESS)(2) against 22 external test inhibitors = 0.707) suggesting the existence of at least two distinct binding modes accessible to ligands within CETP binding pocket. The successful pharmacophores were complemented with strict shape constraints in an attempt to optimize their receiver-operating characteristic (ROC) curve profiles.The validity of our modeling approach was experimentally established by the identification of several CETP inhibitory leads retrieved via in silk screening of the National Cancer Institute (NCI) list of compounds and an in house built database of drugs and agrochemicals. Two hits illustrated low micromolar IC50 values: NSC 40331 (IC50 = 6.5 mu M) and NSC 89508 (IC50 = 1.9 mu M). Active hits were then used to guide synthetic exploration of a new series of CETP inhibitors. (c) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.12.070

文献信息

• DE2903709
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of new cholesteryl ester transfer protein inhibitors via ligand-based pharmacophore modeling and QSAR analysis followed by synthetic exploration
  作者：Reema Abu Khalaf、Ghassan Abu Sheikha、Yasser Bustanji、Mutasem O. Taha

  DOI：10.1016/j.ejmech.2009.12.070

  日期：2010.4

  Cholesteryl ester transfer protein (CETP) is involved in trafficking lipoprotein particles and neutral lipids between HDL and LDL and therefore is considered a valid target for treating dyslipidemic conditions and complications. Pharmacophore modeling and quantitative structure-activity relationship (QSAR) analysis were combined to explore the structural requirments for potent CETP inhibitors. Two pharmacophores emerged in the optimal QSAR equation (r(2) = 0.800, n = 96, F = 72.1. r(LOO)(2) = 0.775, r(PRESS)(2) against 22 external test inhibitors = 0.707) suggesting the existence of at least two distinct binding modes accessible to ligands within CETP binding pocket. The successful pharmacophores were complemented with strict shape constraints in an attempt to optimize their receiver-operating characteristic (ROC) curve profiles.The validity of our modeling approach was experimentally established by the identification of several CETP inhibitory leads retrieved via in silk screening of the National Cancer Institute (NCI) list of compounds and an in house built database of drugs and agrochemicals. Two hits illustrated low micromolar IC50 values: NSC 40331 (IC50 = 6.5 mu M) and NSC 89508 (IC50 = 1.9 mu M). Active hits were then used to guide synthetic exploration of a new series of CETP inhibitors. (c) 2010 Elsevier Masson SAS. All rights reserved.