3-(1,3-dioxoisoindolin-2-yl)benzyl nitrate | 1160791-70-7

• 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: 3-(1,3-dioxoisoindolin-2-yl)benzyl nitrate
• 英文别名: [3-(1,3-dioxoisoindol-2-yl)phenyl]methyl nitrate
• CAS: 1160791-70-7
• 化学式: C₁₅H₁₀N₂O₅
• 分子量: 298.255
• InChiKey: LTYKQEXOGFRBCK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  92.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-[(3-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90%的产率得到3-(1,3-dioxoisoindolin-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

文献信息

• 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].
• USE OF PHTHALIMIDE AND/OR SULPHONAMIDE DERIVATIVES IN THE TREATMENT OF DISEASES WHICH REQUIRE REDUCING THE TNF-alpha LEVELS AND AN EXOGENOUS SOURCE OF NITRIC OXIDE, PHTHALIMIDE DERIVATIVES, SULPHONAMIDE DERIVATIVES, AND A METHOD FOR OBTAINING A SULPHONAMIDE DERIVATIVE
  申请人：Dos Santos Jean Leandro

  公开号：US20100324107A1

  公开（公告）日：2010-12-23

  The present invention refers to the use of phthalimide and/or sulphonamide derivatives with nitric oxide donor properties, which have important activities in increasing the gamma-globin gene expression and anti-inflammatory and analgesic activities, effective in the treatment of hematologic diseases which require reducing the TNF-α levels and an exogenous source of nitric oxide. More particularly, the present invention describes the use of such phthalimide and/or sulphonamide derivatives for the treatment of sickle-cell disease. The invention also has as a novel characteristic the disclosure of new functionalized phthalimide derivatives designed from the prototypes thalidomide and hydroxyurea, and designed rationally through the strategy of molecular hybridization for the treatment of said diseases. The invention still discloses a new method for obtaining a specific sulphonamide derivative which can be used in the preparation of a drug for the treatment of diseases which require reducing the levels of the TNF-α factor and an exogenous source of nitric oxide.
• US8314255B2
  申请人：——

  公开号：US8314255B2

  公开（公告）日：2012-11-20
• US8338474B2
  申请人：——

  公开号：US8338474B2

  公开（公告）日：2012-12-25
• [EN] USE OF PHTHALIMIDE AND/OR SULPHONAMIDE DERIVATIVES IN THE TREATMENT OF DISEASES WHICH REQUIRE REDUCING THE TNF-a LEVELS AND AN EXOGENOUS SOURCE OF NITRIC OXIDE, PHTHALIMIDE DERIVATIVES, SULPHONAMIDE DERIVATIVES, AND A METHOD FOR OBTAINING A SULPHONAM<br/>[FR] UTILISATION DE DÉRIVÉS DE PHTALAMIDE ET/OU DE SULFONAMIDE DANS LE TRAITEMENT DE MALADIES POUR LESQUELLES UNE RÉDUCTION DES TAUX DE TNF-a ET L'UTILISATION D'UNE SOURCE EXOGÈNE D'OXYDE NITRIQUE SONT NÉCESSAIRES, DÉRIVÉS DE PHTALAMIDE, DÉRIVÉS DE SULFON
  申请人：UNICAMP

  公开号：WO2009073940A2

  公开（公告）日：2009-06-18

  The present invention refers to the use of phthalimide and/or sulphonamide derivatives with nitric oxide donor properties, which have important activities in increasing the gamma-globin gene expression and anti-inflammatory and analgesic activities, effective in the treatment of hematologic diseases which require reducing the TNF-α levels and an exogenous source of nitric oxide. More particularly, the present invention describes the use of such phthalimide and/or sulphonamide derivatives for the treatment of sickle-cell diseases. The invention also has as a novel characteristic the disclosure of new functionalized phthalimide derivatives designed from the prototypes thalidomide and hydroxyurea, and designed rationally through the strategy of molecular hybridization for the treatment of said diseases. The invention still discloses a new method for obtaining a specific sulphonamide derivative which can be used in the preparation of a drug for the treatment of diseases which require reducing the levels of the TNF-α factor and an exogenous source of nitric oxide.