4-(1-ethylpropyl)benzoic acid hydrazide | 945484-72-0

• 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-(1-ethylpropyl)benzoic acid hydrazide
• CAS: 945484-72-0
• 化学式: C₁₂H₁₈N₂O
• 分子量: 206.288
• InChiKey: GYHQMZDROSPQIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.19
• 重原子数：
  15.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  55.12
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3-(1-ethylpropyl)-2-hydroxybenzenecarbaldehyde 、 4-(1-ethylpropyl)benzoic acid hydrazide 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 4-(1-ethylpropyl)benzoic acid [3-(1-ethylpropyl)-2-hydroxy-benzylidene]-hydrazide
  参考文献：
  名称：

  Engineered Chimeric Enzymes as Tools for Drug Discovery:  Generating Reliable Bacterial Screens for the Detection, Discovery, and Assessment of Estrogen Receptor Modulators

  摘要：

  Engineered protein-based sensors of ligand binding have emerged as attractive tools for the discovery of therapeutic compounds through simple screening systems. We have previously shown that engineered chimeric enzymes, which combine the ligand-binding domains of nuclear hormone receptors with a highly sensitive thymidylate synthase reporter, yield simple sensors that report the presence of hormone-like compounds through changes in bacterial growth. This work describes an optimized estrogen sensor in Escherichia coli with extraordinary reliability in identifying diverse estrogenic compounds and in differentiating between their agonistic/antagonistic pharmacological effects. The ability of this system to assist the discovery of new estrogen-mimicking compounds was validated by screening a small compound library, which led to the identification of two structurally novel estrogen receptor modulators and the accurate prediction of their agonistic/antagonistic biocharacter in human cells. Strong evidence is presented here that the ability of our sensor to detect ligand binding and recognize pharmacologically critical properties arises from allosteric communication between the artificially combined protein domains, where different ligand-induced conformational changes in the receptor are transmitted to the catalytic domain and translated to distinct levels of enzymic efficiency. To the best of our knowledge, this is one of the first examples of an engineered enzyme with the ability to sense multiple receptor conformations and to be either activated or inactivated depending on the nature of the bound effector molecule. Because the proposed mechanism of ligand dependence is not specific to nuclear hormone receptors, we anticipate that our protein engineering strategy will be applicable to the construction of simple sensors for different classes of (therapeutic) binding proteins.

  DOI：

  10.1021/ja067754j
• 作为产物：
  描述：

  3-苯基戊烷 在 正丁基锂 、 氯化亚砜 、 溴 、 一水合肼 、 N,N-二甲基甲酰胺 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 21.0h， 生成 4-(1-ethylpropyl)benzoic acid hydrazide
  参考文献：
  名称：

  Engineered Chimeric Enzymes as Tools for Drug Discovery:  Generating Reliable Bacterial Screens for the Detection, Discovery, and Assessment of Estrogen Receptor Modulators

  摘要：

  Engineered protein-based sensors of ligand binding have emerged as attractive tools for the discovery of therapeutic compounds through simple screening systems. We have previously shown that engineered chimeric enzymes, which combine the ligand-binding domains of nuclear hormone receptors with a highly sensitive thymidylate synthase reporter, yield simple sensors that report the presence of hormone-like compounds through changes in bacterial growth. This work describes an optimized estrogen sensor in Escherichia coli with extraordinary reliability in identifying diverse estrogenic compounds and in differentiating between their agonistic/antagonistic pharmacological effects. The ability of this system to assist the discovery of new estrogen-mimicking compounds was validated by screening a small compound library, which led to the identification of two structurally novel estrogen receptor modulators and the accurate prediction of their agonistic/antagonistic biocharacter in human cells. Strong evidence is presented here that the ability of our sensor to detect ligand binding and recognize pharmacologically critical properties arises from allosteric communication between the artificially combined protein domains, where different ligand-induced conformational changes in the receptor are transmitted to the catalytic domain and translated to distinct levels of enzymic efficiency. To the best of our knowledge, this is one of the first examples of an engineered enzyme with the ability to sense multiple receptor conformations and to be either activated or inactivated depending on the nature of the bound effector molecule. Because the proposed mechanism of ligand dependence is not specific to nuclear hormone receptors, we anticipate that our protein engineering strategy will be applicable to the construction of simple sensors for different classes of (therapeutic) binding proteins.

  DOI：

  10.1021/ja067754j