2-(4-(hydroxymethyl)phenyl)isoindoline-1,3-dione | 1242469-49-3

• 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-(4-(hydroxymethyl)phenyl)isoindoline-1,3-dione
• 英文别名: 2-[4-(hydroxymethyl)phenyl]-2,3-dihydro-1H-isoindole-1,3-dione；2-[4-(hydroxymethyl)phenyl]isoindole-1,3-dione
• CAS: 1242469-49-3
• 化学式: C₁₅H₁₁NO₃
• 分子量: 253.257
• InChiKey: HKTJCIFLNZNXLP-UHFFFAOYSA-N

物化性质

• 熔点：
  155-158 °C
• 沸点：
  485.9±47.0 °C(Predicted)
• 密度：
  1.402±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-(hydroxymethyl)phenyl)isoindoline-1,3-dione 在 硝酸 、 乙酸酐 、 尿素 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以88%的产率得到4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)benzyl nitrate
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of Novel Hybrid Compounds To Treat Sickle Cell Disease Symptoms

  摘要：

  A novel series of thalidomide derivatives (4a-f) designed by molecular hybridization were synthesized and evaluated in vitro and in vivo for their potential use in the oral treatment of sickle cell disease symptoms. Compounds 4a-f demonstrated analgesic, anti-inflammatory, and NO-donor properties. Compounds 4c and 4d were considered promising candidate drugs and were further evaluated in transgenic sickle cell mice to determine their capacity to reduce the levels of the proinflammatory cytokine tumor necrosis factor alpha (TNF alpha). Unlike hydroxyurea, the compounds reduced the concentrations of TNF alpha to levels similar to those induced with the control dexamethasone (300 mu mol/kg). These compounds are novel lead drug candidates with multiple beneficial actions in the treatment of sickle cell disease symptoms and offer an alternative to hydroxyurea treatment.

  DOI：

  10.1021/jm200531f
• 作为产物：
  描述：

  苯酐 、 对氨基苯甲醇 在 吡啶 作用下， 反应 3.0h， 以63%的产率得到2-(4-(hydroxymethyl)phenyl)isoindoline-1,3-dione
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of Novel Hybrid Compounds To Treat Sickle Cell Disease Symptoms

  摘要：

  A novel series of thalidomide derivatives (4a-f) designed by molecular hybridization were synthesized and evaluated in vitro and in vivo for their potential use in the oral treatment of sickle cell disease symptoms. Compounds 4a-f demonstrated analgesic, anti-inflammatory, and NO-donor properties. Compounds 4c and 4d were considered promising candidate drugs and were further evaluated in transgenic sickle cell mice to determine their capacity to reduce the levels of the proinflammatory cytokine tumor necrosis factor alpha (TNF alpha). Unlike hydroxyurea, the compounds reduced the concentrations of TNF alpha to levels similar to those induced with the control dexamethasone (300 mu mol/kg). These compounds are novel lead drug candidates with multiple beneficial actions in the treatment of sickle cell disease symptoms and offer an alternative to hydroxyurea treatment.

  DOI：

  10.1021/jm200531f

文献信息

• Design, Synthesis, and Pharmacological Evaluation of Novel Hybrid Compounds To Treat Sickle Cell Disease Symptoms
  作者：Jean Leandro dos Santos、Carolina Lanaro、Lídia Moreira Lima、Sheley Gambero、Carla Fernanda Franco-Penteado、Magna Suzana Alexandre-Moreira、Marlene Wade、Shobha Yerigenahally、Abdullah Kutlar、Steffen E. Meiler、Fernando Ferreira Costa、ManChin Chung

  DOI：10.1021/jm200531f

  日期：2011.8.25

  A novel series of thalidomide derivatives (4a-f) designed by molecular hybridization were synthesized and evaluated in vitro and in vivo for their potential use in the oral treatment of sickle cell disease symptoms. Compounds 4a-f demonstrated analgesic, anti-inflammatory, and NO-donor properties. Compounds 4c and 4d were considered promising candidate drugs and were further evaluated in transgenic sickle cell mice to determine their capacity to reduce the levels of the proinflammatory cytokine tumor necrosis factor alpha (TNF alpha). Unlike hydroxyurea, the compounds reduced the concentrations of TNF alpha to levels similar to those induced with the control dexamethasone (300 mu mol/kg). These compounds are novel lead drug candidates with multiple beneficial actions in the treatment of sickle cell disease symptoms and offer an alternative to hydroxyurea treatment.
• Antiplatelet activity and TNF-α release inhibition of phthalimide derivatives useful to treat sickle cell anemia
  作者：Rafael C. Chelucci、Isabela J. de Oliveira、Karina P. Barbieri、Maria E. Lopes-Pires、Marisa C. Polesi、Diego E. Chiba、Iracilda Z. Carlos、Sisi Marcondes、Jean L. Dos Santos、ManChin Chung

  DOI：10.1007/s00044-019-02371-z

  日期：2019.8

  Sickle Cell Anemia (SCA) is one of the most prevalent hereditary hematological diseases worldwide. The disease is characterized by chronic inflammation, hypercoagulable state, and pro-thrombotic profile, which lead the vaso-occlusive process. In this work, we described the antiplatelet activity and the ability to reduce tumor necrosis factor-alpha (TNF-) levels of phthalimide derivatives. All compounds inhibited platelet aggregation induced by collagen and adenosine diphosphate, at levels ranging from 26.0 to 74.2% and 30.7 to 79.6%, respectively. The compounds exhibited reduced bleeding time compared to acetylsalicylic acid (ASA). Moreover, compounds 4c and 10c inhibited TNF- levels at 73.5% and 65.0%, respectively. These findings suggest that phthalimide derivatives 4c and 10c are promising lead compounds useful to prevent vaso-occlusion and inflammation associated with the sickle cell anemia.[GRAPHICS].