(+)-5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]-1H-isoindol-1,3(2H)-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: (+)-5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]-1H-isoindol-1,3(2H)-dione
• 英文别名: (+)-5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]-1H-isoindole-1,3(2H)-dione；5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-3H-1-benzofuran-5-yl]isoindole-1,3-dione
• 化学式: C₃₀H₃₁NO₅
• 分子量: 485.58
• InChiKey: ALDUKKYCTCRQKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  36
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4,5-二甲氧基邻苯二甲酸酐 、 (+)-2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-amine 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 1-羟基苯并三唑 在 氩 、 aqueous solution 、 sodium hydroxide 、 乙酸乙酯 、 碳酸氢钠 、 magnesium sulfate 、 crude product 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 17.0h， 以to obtain a crude product of (+)-5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]-1H-isoindol-1,3(2H)-dione (8.40 g)的产率得到(+)-5,6-dimethoxy-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]-1H-isoindol-1,3(2H)-dione
  参考文献：
  名称：

  Solid compositions containing compounds unstable to oxygen and method for stabilization thereof

  摘要：

  本发明旨在稳定一种含氮融合杂环化合物的固体组合物，该化合物不稳定于氧气，以提供稳定的药物制剂。可以通过保持平衡含水量在10％或以上和/或添加抗坏血酸或其盐来实现稳定，通过预先应用不含遮光剂的薄膜涂层，或通过应用氧气屏障包装、惰性气体替换包装、真空包装和带有氧气吸收剂的密封包装中的一种或多种包装来实现稳定。

  公开号：

  US20050118202A1

文献信息

• Benzofuran derivatives, their production and use
  申请人：——

  公开号：US20020160996A1

  公开（公告）日：2002-10-31

  Compounds represented by the formula: 1 wherein R 1 and R 2 are hydrogen atom, a hydrocarbon group or a heterocyclic group, or R 1 and R 2 may form, together with the adjacent carbon atom, a 3- to 8-membered homocyclic or heterocyclic ring, W indicates (i) a group represented by the formula: 2 wherein ring B indicates a 5- to 7-membered ring, or (ii) a group represented by the formula: 3 wherein R 4 indicates (1) an aliphatic hydrocarbon group, which may be substituted with an aromatic group, or (2) an acyl group containing an aromatic group, R 5 is hydrogen atom, a C 1-6 alkyl, or an acyl group, provided that, when W is Wa, R 3 is hydrogen atom, a hydrocarbon group or a heterocyclic group, when W is Wb, R 3 indicates a C 6-14 aryl group, or salts thereof or prodrugs thereof have an excellent action to inhibit neurodegeneration and the like as well as an excellent brain penetrability and are low in the toxicity, thereby being useful as prophylactic or therapeutic drugs for nerve degenerative diseases and the like.

  由以下公式代表的化合物： 其中 R1 和 R2 是氢原子、烃基或杂环基，或者 R1 和 R2 可以与相邻的碳原子一起形成 3 至 8 个成员的同环或杂环环，W 表示 (i) 由以下公式代表的基团： 其中环 B 表示一个 5 至 7 个成员的环，或者 (ii) 由以下公式代表的基团： 其中 R4 表示 (1) 可以用芳香基取代的脂肪烃基，或者 (2) 含有芳香基的酰基，R5 是氢原子、C1-6 烷基或酰基，提供当 W 是 Wa 时，R3 是氢原子、烃基或杂环基，当 W 是 Wb 时，R3 表示一个 C6-14 芳基，或其盐或前药具有优异的抑制神经退行性等作用，以及出色的脑透过性，毒性低，因此可用作预防或治疗神经退行性疾病等的药物。
• Solid compositions containing compounds unstable to oxygen and method for stabilization thereof
  申请人：Yamashita Akio

  公开号：US20050118202A1

  公开（公告）日：2005-06-02

  The present invention aims at stabilizing a solid composition containing a nitrogenous fused-heterocycle compound unstable to oxygen to provide a stable pharmaceutical preparation. The stabilization can be attained by keeping the equilibrium moisture content at 10% or above and/or adding ascorbic acid or a salt thereof, by preliminarily applying a film coating free from light blocking agents, or by applying one or more packaging selected from among oxygen-barrier packaging, inert gas replacement packaging, vacuum packaging and sealing packaging with an oxygen absorber.

  本发明旨在稳定一种含氮融合杂环化合物的固体组合物，该化合物不稳定于氧气，以提供稳定的药物制剂。可以通过保持平衡含水量在10％或以上和/或添加抗坏血酸或其盐来实现稳定，通过预先应用不含遮光剂的薄膜涂层，或通过应用氧气屏障包装、惰性气体替换包装、真空包装和带有氧气吸收剂的密封包装中的一种或多种包装来实现稳定。
• Promoters for the proliferation and differentiation of stem cells and/or neuron precursor cells
  申请人：——

  公开号：US20040034049A1

  公开（公告）日：2004-02-19

  An agent for promoting the proliferation or differentiation of a stem cell and/or neural progenitor cell, comprising a compound represented by Formula: 1 wherein each of R 1 and R 2 is H, a hydrocarbon group or a heterocyclic group, or taken together with the adjacent carbon atom to form a ring, R 3 is H, a hydrocarbon group or a heterocyclic group, W is a group represented by Formula: 2 wherein Ring A is an optionally substituted benzene ring, Ring B is an optionally substituted 5- to 7-membered nitrogen-containing heterocyclic ring, R 4 is an acyl group having an aliphatic hydrocarbon group, which is substituted by an aromatic group and may have a further substitutent, or aromatic group, R 5 is H, C 1-6 alkyl or acyl, R 4c is an aromatic group, an aliphatic hydrocarbon group or acyl, and X is O or S; Y is O, S or NH, Ring C is an optionally substituted benzene ring, or a salt or prodrug thereof is provided.

  一种用于促进干细胞和/或神经前体细胞增殖或分化的药剂，包括由公式1表示的化合物，其中R1和R2中的每一个是H、烃基或杂环基，或与相邻的碳原子结合形成环，R3是H、烃基或杂环基，W是由公式2表示的基团，其中环A是可选取代的苯环，环B是可选取代的含氮5-至7元杂环环，R4是取代芳香基的脂肪烃基的酰基，可以有进一步的取代基，或芳香基，R5是H、C1-6烷基或酰基，R4是芳香基、脂肪烃基或酰基，X是O或S；Y是O、S或NH，环C是可选取代的苯环，或其盐或前药。
• Agents for promoting the proliferation or differentiation of stem cells or neural progenitor cells
  申请人：Okawa Shigenori

  公开号：US20090012081A1

  公开（公告）日：2009-01-08

  An agent for promoting the proliferation or differentiation of a stem cell and/or neural progenitor cell, comprising a compound represented by Formula: wherein each of R 1 and R 2 is H, a hydrocarbon group or a heterocyclic group, or taken together with the adjacent carbon atom to form a ring, R 3 is H, a hydrocarbon group or a heterocyclic group, W is a group represented by Formula: wherein Ring A is an optionally substituted benzene ring, Ring B is an optionally substituted 5- to 7-membered nitrogen-containing heterocyclic ring, R 4 is an acyl group having an aliphatic hydrocarbon group, which is substituted by an aromatic group and may have a further substitutent, or aromatic group, R 5 is H, C 1-6 alkyl or acyl, R 4c is an aromatic group, an aliphatic hydrocarbon group or acyl, and X is O or S; Y is O, S or NH, Ring C is an optionally substituted benzene ring, or a salt or prodrug thereof is provided.

  一种用于促进干细胞和/或神经祖细胞增殖或分化的药剂，包括由下式表示的化合物：其中R1和R2中的每一个是H、烃基或杂环基，或与相邻的碳原子结合形成环，R3是H、烃基或杂环基，W是由下式表示的基团：其中环A是可选取代的苯环，环B是可选取代的含氮杂环5-至7-元环，R4是取代芳基的脂肪族烃基的酰基，可以具有进一步的取代基或芳基，或者是芳基，R5是H、C1-6烷基或酰基，R4是芳基、脂肪族烃基或酰基，X是O或S；Y是O、S或NH，环C是可选取代的苯环，或其盐或前药。
• Benzofuran derivatives, process for the preparation of the same and uses thereof
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06479536B1

  公开（公告）日：2002-11-12

  Compounds represented by the formula: wherein R1 and R2 are hydrogen atom, a hydrocarbon group or a heterocyclic group, or R1 and R2 may form, together with the adjacent carbon atom, a 3- to 8-membered homocyclic or heterocyclic ring, W indicates (i) a group represented by the formula:  wherein ring B indicates a 5- to 7-membered ring, or (ii) a group represented by the formula:  wherein R4 indicates (1) an aliphatic hydrocarbon group, which may be substituted with an aromatic group, or (2) an acyl group containing an aromatic group, R5 is hydrogen atom, a C1-6 alkyl, or an acyl group, provided that, when W is Wa, R3 is hydrogen atom, a hydrocarbon group or a heterocyclic group, when W is Wb, R3 indicates a C6-14 aryl group, or salts thereof or prodrugs thereof have an excellent action to inhibit neurodegeneration and the like as well as an excellent brain penetrability and are low in the toxicity, thereby being useful as prophylactic or therapeutic drugs for nerve degenerative diseases and the like.

  该化合物的式子为：其中R1和R2是氢原子、烃基或杂环基，或者R1和R2可以与相邻的碳原子一起形成3-至8-成员的同环或异环环；W表示(i)由公式表示的基团：其中环B表示5-至7-成员环，或(ii)由公式表示的基团：其中R4表示(1)烷基烃基，可以用芳香基取代，或(2)含有芳香基的酰基基团，R5是氢原子、C1-6烷基或酰基基团，但当W为Wa时，R3为氢原子、烃基或杂环基，当W为Wb时，R3表示C6-14芳基，或其盐或前药具有出色的抑制神经退行性等作用，以及出色的脑穿透性，毒性低，因此可用作神经退行性疾病的预防或治疗药物等。