[2-(3,4-dichloro)phenyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid | 285552-82-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: [2-(3,4-dichloro)phenyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid
• 英文别名: 2-(3,4-Dichlorophenyl)-1,3-dioxoisoindoline-5-carboxylic acid；2-(3,4-dichlorophenyl)-1,3-dioxoisoindole-5-carboxylic acid
• CAS: 285552-82-1
• 化学式: C₁₅H₇Cl₂NO₄
• mdl: MFCD00406014
• 分子量: 336.131
• InChiKey: WQJRCVALNJFUHE-UHFFFAOYSA-N

物化性质

• 熔点：
  290-292 °C
• 沸点：
  597.3±60.0 °C(Predicted)
• 密度：
  1.654±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  α-(aminomethyl)-4-[2-(1-methylethoxy)phenyl]-1-piperazineethanol 、 [2-(3,4-dichloro)phenyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以32%的产率得到2-(3,4-Dichloro-phenyl)-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid {2-hydroxy-3-[4-(2-isopropoxy-phenyl)-piperazin-1-yl]-propyl}-amide
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of Phthalimide-Phenylpiperazines:  A Novel Series of Potent and Selective α_1a-Adrenergic Receptor Antagonists

  摘要：

  Beginning from the screening hit and literature alpha(1)-adrenergic compounds, a hybridized basic skeleton A was proposed as the pharmacophore for potent and selective alpha(1a)-AR antagonists. Introduction of a hydroxy group to increase the flexibility afforded B which served as the screening model and resulted in the identification of the second-generation lead 1. Using the Topliss approach, a number of potent and selective alpha(1a)-AR antagonists were discovered. In all cases, binding affinity and selectivity at the alpha(1a)-AR of S-hydroxy enantiomers were higher than those of the R-hydroxy enantiomers. As compared to the des-hydroxy analogues, the S-hydroxy enantiomers had slightly lower binding affinity at alpha(1a)-AR but gained more than 2-fold selectivity for alpha(1a)-AR over alpha(1b)-AR, and 2- to 6-fold selectivity for alpha(1a)-AR over alpha(1d)-AR. They also had less cross activities against a panel of 25-35 peripheral and CNS receptors. The S-hydroxy enantiomers 23 and 24 (K-i = 0.29 nM, 0.33 nM; alpha(1b)/alpha(1a) >5690, >6060; alpha(1d)/alpha(1a) = 186, 158, respectively) were slightly less potent but much more selective at alpha(1a)-AR than tamsulosin (K-i = 0.13 nM, alpha(1d)/alpha(1a)= 14.8, alpha(1d)/alpha(1a) = 1.4). In the functional assay, the S-hydroxy enantiomers 20, 23, and 24 were less potent than tamsulosin in inhibiting contractions of rat prostate tissue but more selective in the inhibition of tissue contractions of rat prostate versus rat aorta. Compound 24 was selected as the development candidate for the treatment of BPH.

  DOI：

  10.1021/jm9905918
• 作为产物：
  描述：

  3,4-二氯苯胺 、 偏苯三酸酐 在 溶剂黄146 作用下， 以 乙醚 为溶剂， 生成 [2-(3,4-dichloro)phenyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid
  参考文献：
  名称：

  环状酰亚胺（甲基邻苯二甲酰亚胺，羧酸邻苯二甲酰亚胺和衣康酰亚胺）的合成及其抗真菌潜力的评估。

  摘要：

  背景技术本文描述了环状酰亚胺的三个不同亚家族的合成：甲基邻苯二甲酰亚胺，羧酸邻苯二甲酰亚胺和衣康酰亚胺。方法使用适当的酸酐和不同的芳族胺，使用手动Topliss方法反应，可得到15种化合物（每个子家族5种）。通过光谱数据（IR和NMR）证实了它们的结构。通过肉汤微量稀释研究合成的化合物的抗真菌活性，以确定最小抑制浓度（MIC）。还针对最具活性的物质评估了抑制生物膜形成或破坏成熟的白色念珠菌生物膜的能力。结果结果表明，只有衣康酰亚胺亚胺11-15表现出强大而有希望的抗真菌特性，MIC100在1至64μgmL-1之间，比参考药物氟康唑的功效高出几倍。在浓度为64μgmL-1的情况下，化合物11-15抑制了64％至95％的生物膜形成，并破坏了78％至99％的成熟生物膜。在计算机模拟评估中进行了ADME（吸收，分布，代谢和排泄），以预测所研究的分子是否为良好的候选药物。结论Itaconimides

  DOI：

  10.2174/1573406412666160229150833

文献信息

• Synthesis of Cyclic Imides (Methylphtalimides, Carboxylic Acid Phtalimides and Itaconimides) and Evaluation of their Antifungal Potential
  作者：Dorimar Stiz、Rogério Corrêa、Felicia D. D';Auria、Giovanna Simonetti、Valdir Cechinel-Filho

  DOI：10.2174/1573406412666160229150833

  日期：2016.9.27

  BACKGROUND This paper describes the synthesis of three different subfamilies of cyclic imides: methylphtalimides, carboxyl acid phtalimides and itaconimides. METHODS Fifteen compounds (five of each sub-family) were obtained by the reaction of appropriated anhydrides and different aromatic amines, using the manual Topliss method. Their structures were confirmed by spectral data (IR and NMR). The antifungal

  背景技术本文描述了环状酰亚胺的三个不同亚家族的合成：甲基邻苯二甲酰亚胺，羧酸邻苯二甲酰亚胺和衣康酰亚胺。方法使用适当的酸酐和不同的芳族胺，使用手动Topliss方法反应，可得到15种化合物（每个子家族5种）。通过光谱数据（IR和NMR）证实了它们的结构。通过肉汤微量稀释研究合成的化合物的抗真菌活性，以确定最小抑制浓度（MIC）。还针对最具活性的物质评估了抑制生物膜形成或破坏成熟的白色念珠菌生物膜的能力。结果结果表明，只有衣康酰亚胺亚胺11-15表现出强大而有希望的抗真菌特性，MIC100在1至64μgmL-1之间，比参考药物氟康唑的功效高出几倍。在浓度为64μgmL-1的情况下，化合物11-15抑制了64％至95％的生物膜形成，并破坏了78％至99％的成熟生物膜。在计算机模拟评估中进行了ADME（吸收，分布，代谢和排泄），以预测所研究的分子是否为良好的候选药物。结论Itaconimides
• Design, Synthesis, and Structure−Activity Relationships of Phthalimide-Phenylpiperazines:  A Novel Series of Potent and Selective α₁_a-Adrenergic Receptor Antagonists
  作者：Gee-Hong Kuo、Catherine Prouty、William V. Murray、Virginia Pulito、Linda Jolliffe、Peter Cheung、Sally Varga、Mary Evangelisto、Jian Wang

  DOI：10.1021/jm9905918

  日期：2000.6.1

  Beginning from the screening hit and literature alpha(1)-adrenergic compounds, a hybridized basic skeleton A was proposed as the pharmacophore for potent and selective alpha(1a)-AR antagonists. Introduction of a hydroxy group to increase the flexibility afforded B which served as the screening model and resulted in the identification of the second-generation lead 1. Using the Topliss approach, a number of potent and selective alpha(1a)-AR antagonists were discovered. In all cases, binding affinity and selectivity at the alpha(1a)-AR of S-hydroxy enantiomers were higher than those of the R-hydroxy enantiomers. As compared to the des-hydroxy analogues, the S-hydroxy enantiomers had slightly lower binding affinity at alpha(1a)-AR but gained more than 2-fold selectivity for alpha(1a)-AR over alpha(1b)-AR, and 2- to 6-fold selectivity for alpha(1a)-AR over alpha(1d)-AR. They also had less cross activities against a panel of 25-35 peripheral and CNS receptors. The S-hydroxy enantiomers 23 and 24 (K-i = 0.29 nM, 0.33 nM; alpha(1b)/alpha(1a) >5690, >6060; alpha(1d)/alpha(1a) = 186, 158, respectively) were slightly less potent but much more selective at alpha(1a)-AR than tamsulosin (K-i = 0.13 nM, alpha(1d)/alpha(1a)= 14.8, alpha(1d)/alpha(1a) = 1.4). In the functional assay, the S-hydroxy enantiomers 20, 23, and 24 were less potent than tamsulosin in inhibiting contractions of rat prostate tissue but more selective in the inhibition of tissue contractions of rat prostate versus rat aorta. Compound 24 was selected as the development candidate for the treatment of BPH.