2-(5,6-dihydroxyhexyl)-1H-isoindole-1,3(2H)-dione | 156917-95-2

• 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-(5,6-dihydroxyhexyl)-1H-isoindole-1,3(2H)-dione
• 英文别名: 2-(5,6-Dihydroxyhexyl)isoindole-1,3-dione
• CAS: 156917-95-2
• 化学式: C₁₄H₁₇NO₄
• 分子量: 263.293
• InChiKey: BHVGJINMAPLNMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  77.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(5,6-dihydroxyhexyl)-1H-isoindole-1,3(2H)-dione 在 4-甲基苯磺酸吡啶 、 一水合肼 作用下， 以 四氢呋喃 为溶剂， 反应 42.0h， 生成 4-(2,2-dimethyl-1,3-dioxolan-4-yl)butan-1-amine
  参考文献：
  名称：

  Amodiaquine analogues containing NO-donor substructures: Synthesis and their preliminary evaluation as potential tools in the treatment of cerebral malaria

  摘要：

  The synthesis and physico-chemical properties of novel compounds obtained by conjugation of amodiaquine with moieties containing either furoxan or nitrooxy NO-donor substructures are described. The synthesised compounds were tested in vitro against both the chloroquine sensitive, 010 and the chloroquine resistant, W-2 strains of Plasmodium falciparum (P falciparum). Most of the compounds showed an antiplasmodial activity comparable to that of the parent drug. By comparing the activities of simple related structures devoid of the ability to release NO, it appears that the contribution of NO to the antiplasmodial action in vitro is marginal. All the compounds were able to relax rat aorta strips with a NO-dependent mechanism, thus showing their capacity to release NO in the vessels. A preliminary in vivo study using Plasmodium berghei ANKA-infected mice showed a trend for prolonged survival of mice with cerebral malaria treated with compound 40, which is potent and fast amodiaquine-derived NO-donor, when compared with amodiaquine alone or with compound 31, a milder NO-donor. The two compounds showed in vivo antiplasmodial activity similar to that of amodiaquine. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.02.029
• 作为产物：
  描述：

  5-己烯-1-醇 在 potassium permanganate 、 三乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 水 、 丙酮 、 乙腈 为溶剂， 反应 72.0h， 生成 2-(5,6-dihydroxyhexyl)-1H-isoindole-1,3(2H)-dione
  参考文献：
  名称：

  Amodiaquine analogues containing NO-donor substructures: Synthesis and their preliminary evaluation as potential tools in the treatment of cerebral malaria

  摘要：

  The synthesis and physico-chemical properties of novel compounds obtained by conjugation of amodiaquine with moieties containing either furoxan or nitrooxy NO-donor substructures are described. The synthesised compounds were tested in vitro against both the chloroquine sensitive, 010 and the chloroquine resistant, W-2 strains of Plasmodium falciparum (P falciparum). Most of the compounds showed an antiplasmodial activity comparable to that of the parent drug. By comparing the activities of simple related structures devoid of the ability to release NO, it appears that the contribution of NO to the antiplasmodial action in vitro is marginal. All the compounds were able to relax rat aorta strips with a NO-dependent mechanism, thus showing their capacity to release NO in the vessels. A preliminary in vivo study using Plasmodium berghei ANKA-infected mice showed a trend for prolonged survival of mice with cerebral malaria treated with compound 40, which is potent and fast amodiaquine-derived NO-donor, when compared with amodiaquine alone or with compound 31, a milder NO-donor. The two compounds showed in vivo antiplasmodial activity similar to that of amodiaquine. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.02.029

文献信息

• BIODEGRADABLE POLYETHYLENE GLYCOL DERIVATIVE HAVING CYCLIC BENZYLIDENE ACETAL LINKER
  申请人：NOF CORPORATION

  公开号：US20180078651A1

  公开（公告）日：2018-03-22

  A biodegradable polyethylene glycol derivative in which a polyethylene glycol chain is linked by an acetal linker capable of accurately controlling the hydrolysis rate under different pH environments in the living body, and whose division rate into a polyethylene glycol chain of low molecular weight in the living body can be accurately controlled. The biodegradable polyethylene glycol derivative is represented by formula (1) or formula (2) as described.

  一种可生物降解的聚乙二醇衍生物，其中聚乙二醇链通过缩醛连接剂连接，该连接剂能够在不同pH环境下精确控制在生物体内的水解速率，并且其分裂速率能够精确控制为低分子量的聚乙二醇链。该可生物降解的聚乙二醇衍生物由式（1）或式（2）所示。
• HYDROPHILIC POLYMER DERIVATIVE HAVING CYCLIC BENZYLIDENE ACETAL LINKER
  申请人：NOF Corporation

  公开号：EP3130587A1

  公开（公告）日：2017-02-15

  To provide a hydrophilic polymer derivative having an acetal linker whose hydrolysis rate at pH of a weakly acidic environment in the living body can be accurately controlled, and which does not liberate a low molecular weight substance other than the hydrophilic polymer chain and the drug or the like connected, more specifically, a low molecular weight aldehyde, at the time of hydrolysis. The present invention relates to a hydrophilic polymer derivative having a cyclic benzylidene acetal linker represented by the following formula (1): wherein R1 and R6 are each independently a hydrogen atom or a hydrocarbon group; R2, R3, R4 and R5 are each independently an electron-withdrawing or electron-donating substituent or a hydrogen atom; X1 is a chemically reactive functional group; P is a hydrophilic polymer; s is 1 or 2, t is 0 or 1, and s + t is 1 or 2; w is an integer of 1 to 8; and Z1 and Z2 are each independently a selected divalent spacer.

  提供一种具有缩醛连接体的亲水性聚合物衍生物，其在生物体内弱酸性环境的 pH 值下的水解速度可精确控制，并且在水解时不会释放出除亲水性聚合物链和药物或类似物连接的低分子量物质，更具体地说，不会释放出低分子量醛。本发明涉及一种亲水性聚合物衍生物，它具有由下式（1）表示的环状亚苄基缩醛连接体： 其中 R1 和 R6 各自独立地为氢原子或碳氢基团；R2、R3、R4 和 R5 各自独立地为取电子或供电子取代基或氢原子；X1 为化学活性官能团；P 为亲水性聚合物；s 为 1 或 2，t 为 0 或 1，s + t 为 1 或 2；w 为 1 至 8 的整数；Z1 和 Z2 各自独立地为选定的二价间隔物。
• LIPID DERIVATIVE IN WHICH HYDROPHILIC POLYMERS ARE BOUND VIA CYCLIC BENZYLIDENE ACETAL LINKERS
  申请人：NOF Corporation

  公开号：EP3357514A1

  公开（公告）日：2018-08-08

  To provide a lipid derivative in which a hydrophilic polymer is bound through an acetal linker, and which can accurately control a hydrolysis rate at the pH of the weakly acidic environment in the living body to detach the hydrophilic polymer from a lipid membrane structure. A lipid derivative in which a hydrophilic polymer is bound through a cyclic benzylidene acetal linker represented by formula (1) : wherein, R1 and R6 are each independently a hydrogen atom or a hydrocarbon group; R2, R3, R4 and R5 are each independently an electron-withdrawing or electron-donating substituent or a hydrogen atom; R7 is a hydrocarbon group having from 8 to 24 carbon atoms, an acyl group having from 8 to 24 carbon atoms, a cholesterol derivative, a glycerolipid, a phospholipid or a sphingolipid; P is a hydrophilic polymer; s is 1 or 2, t is 0 or 1, and s + t is 1 or 2; and Z1 and Z2 are each independently a selected divalent spacer.

  提供一种脂质衍生物，其中亲水性聚合物通过乙缩醛连接体结合，并能在生物体内弱酸性环境的 pH 值下准确控制水解速度，使亲水性聚合物从脂质膜结构中分离。一种脂质衍生物，其中的亲水性聚合物通过环状亚苄基缩醛连接体结合，连接体由式（1）表示： 其中，R1 和 R6 各自独立地为氢原子或烃基；R2、R3、R4 和 R5 各自独立地为取电子或供电子取代基或氢原子；R7 是具有 8 至 24 个碳原子的烃基、具有 8 至 24 个碳原子的酰基、胆固醇衍生物、甘油酯、磷脂或鞘磷脂；P 是亲水性聚合物；s 是 1 或 2，t 是 0 或 1，s + t 是 1 或 2；以及 Z1 和 Z2 各自独立地是选定的二价间隔物。
• BIODEGRADABLE HYDROGEL HAVING CYCLIC BENZYLIDENE ACETAL STRUCTURE
  申请人：NOF Corporation

  公开号：EP3438155A1

  公开（公告）日：2019-02-06

  To provide a biodegradable hydrogel having an acetal structure whose hydrolysis rate under different pH environments in the living body can be accurately controlled. A hydrogel obtained by crosslinking a polyalkylene glycol derivative having a cyclic benzylidene acetal structure represented by formula (1) shown below with a crosslinking agent. In formula (1), R1 and R6 are each independently a hydrogen atom or a hydrocarbon group; R2, R3, R4 and R5 are each independently an electron-withdrawing or electron-donating substituent or a hydrogen atom; s is 1 or 2, t is 0 or 1, and s + t is 1 or 2; P1 is a polyalkylene glycol having the number of terminals from 2 to 8; Z1 and Z2 are each independently a selected divalent spacer; W1 is an integer of 2 to 8 and is equal to the number of terminals of the polyalkylene glycol; and X1 is a chemically reactive functional group.

  提供一种具有缩醛结构的可生物降解水凝胶，其在生物体内不同 pH 值环境下的水解速率可得到精确控制。一种水凝胶，由具有下式（1）所示环状亚苄基缩醛结构的聚亚烷基二醇衍生物与一种交联剂交联而成。 在式 (1) 中，R1 和 R6 各自独立地为氢原子或烃基；R2、R3、R4 和 R5 各自独立地为取电子或供电子取代基或氢原子；s 为 1 或 2，t 为 0 或 1，s + t 为 1 或 2；P1 是端子数为 2 至 8 的聚亚烷基二醇；Z1 和 Z2 各自独立地是选定的二价间隔物；W1 是 2 至 8 的整数，且等于聚亚烷基二醇的端子数；以及 X1 是化学活性官能团。
• Antibody-drug conjugate having cyclic benzylidene acetal linker
  申请人：NOF CORPORATION

  公开号：US10377837B2

  公开（公告）日：2019-08-13

  An antibody-drug conjugate having a cyclic benzylidene acetal linker represented by formula (1) or formula (2), wherein Y is an antibody; D is a drug; R1 and R6 are each independently a hydrogen atom or a hydrocarbon group; R2, R3, R4 and R5 are each independently an electron-withdrawing or electron-donating substituent or a hydrogen atom; s is 1 or 2, t is 0 or 1, and s+t is 1 or 2; w is an integer of 1 to 20; and Z1 and Z2 are each independently a selected divalent spacer:

  一种抗体-药物共轭物，具有由式（1）或式（2）表示的环状亚苄基缩醛连接体，其中 Y 是抗体；D 是药物；R1 和 R6 各自独立地是氢原子或烃基；R2、R3、R4 和 R5 各自独立地是一个取电子或供电子的取代基或一个氢原子；s 是 1 或 2，t 是 0 或 1，s+t 是 1 或 2；w 是 1 至 20 的整数；以及 Z1 和 Z2 各自独立地是一个选定的二价间隔物：