4-(3-(1,3-dioxoisoindolin-2-yl)propoxy)-3-methoxybenzaldehyde

• 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: 4-(3-(1,3-dioxoisoindolin-2-yl)propoxy)-3-methoxybenzaldehyde
• 英文别名: 4-[3-(1,3-dioxoisoindol-2-yl)propoxy]-3-methoxybenzaldehyde
• 化学式: C₁₉H₁₇NO₅
• 分子量: 339.348
• InChiKey: LTRXFHCJRSNOJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-氧酰肼-2H-1-苯并吡喃-3-羧酸 、 4-(3-(1,3-dioxoisoindolin-2-yl)propoxy)-3-methoxybenzaldehyde 在 对甲苯磺酸 作用下， 以 乙醇 为溶剂， 以69%的产率得到(E)-N'-(4-(3-(1,3-dioxoisoindolin-2-yl)propoxy)-3-methoxybenzylidene)-2-oxo-2H-chromene-3-carbohydrazide
  参考文献：
  名称：

  新型邻苯二甲酰亚胺-席夫碱-香豆素杂种作为有效的α-葡萄糖苷酶抑制剂的设计，合成和生物学评价

  摘要：

  我们设计并合成了邻苯二甲酰亚胺-席夫碱-香豆素杂种8a - b，9a - d，10a - b和11a - d，并评估了它们对这种酶的酵母形式的α-葡萄糖苷酶抑制潜力。为了合成标题化合物4-羟基苯甲醛，4-羟基-3-甲氧基苯甲醛，2-羟基苯甲醛，2-羟基苯甲醛衍生物，香豆素-3-碳酰肼和香豆素-7-酰氧基-乙酰肼。体外对α-葡萄糖苷酶的抑制作用表明，所有合成的化合物均对IC 50表现出出色的α-葡萄糖苷酶抑制作用与IC 50值为750.0±12.0 µM的标准抑制剂阿卡波糖相比，该值介于85.2±1.7至577.7±7.5 µM之间。最有效的化合物是带有香豆素-3-碳酰肼部分的4-羟基苯甲醛衍生物8a，带有香豆素-7-酰氧基-乙酰肼部分的2-羟基-5-硝基苯甲醛衍生物11d和带有香豆素-3-的2-羟基-5-硝基苯甲醛衍生物9d。 3-碳酰肼部分。进行了分子对接研究以了解最具活性的化合物与标准

  DOI：

  10.1007/s11696-020-01246-7
• 作为产物：
  描述：

  邻苯二甲酸亚胺 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 16.0h， 生成 4-(3-(1,3-dioxoisoindolin-2-yl)propoxy)-3-methoxybenzaldehyde
  参考文献：
  名称：

  Discovery of imidazopyridines containing isoindoline-1,3-dione framework as a new class of BACE1 inhibitors: Design, synthesis and SAR analysis

  摘要：

  Alzheimer's disease is characterized by chronic neurodegeneration leading to dementia. The main cause of neurodegeneration is considered to be the accumulation of amyloid-beta. Inhibiting BACE1 is a well studied approach to lower the burden of amyloid-beta aggregates. We designed a series of imidazopyridines-based compounds bearing phthalimide moieties as inhibitors of BACE1. The compounds 8a-o were synthesized by the Groebke Blackburn Bienayme three-component reaction of heteroaromatic amidines, aldehydes and isocyanides. Evaluating the BACE1 inhibitory effects of the synthesized compounds revealed that introducing an aminocyclohexyl moiety in the imidazopyridine core resulted in a significant improvement in its BACE1 inhibitory potential. In this regard, compound 8e was the most potent against BACE1 with an IC50 value of 2.84 (+/- 0.95) mu M. Molecular docking revealed that the nitrogen atom of imidazopyridines and the oxygen atom of the phenoxypropyl linker were involved in hydrogen bound interactions with Asp228 and Asp32 of BACE1 active site, respectively. The phthalimide moiety oriented toward the flap pocket and interacted with phe108, 11e110, Trp115, 11e118 through van der Waal's and hydrophobic interactions. These findings demonstrate that imidazopyridines-based compounds bearing phthalimide moiety have the potential to decrease amyloid-beta levels and ameliorate the symptoms of Alzheimer's disease. (C) 2017 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2017.06.040

文献信息

• Synthesis and Characterization of Novel Phthalimide-pyrano[3,2-<i>c</i> ]chromene and Phthalimide-pyrano-2-one Hybrids
  作者：Bilqees Sameem、Mina Saeedi、Mohammad Mahdavi、Hamid Nadri、Fahimeh Vafadarnejad、Mohsen Amini

  DOI：10.1002/jhet.3204

  日期：2018.7

  exploration because of its immense pharmacological potential. In this pursuit, a series of phthalimide‐chromen and phthalimide‐pyran‐2‐one hybrids were synthesized in efficient yields via one‐pot multicomponent reaction of aldehyde linked to phthalimide moiety, 4‐hydroxy coumarin/4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one, and malanonitrile by Knoevenagel reaction at room temperature in the presence of DABCO

  由于其巨大的药理潜力，香豆素骨架具有广阔的前景。在这种追求下，通过与一邻苯二甲酰亚胺基团（4-羟基香豆素/ 4-羟基-6-甲基-苯甲酰胺）连接的醛的一锅多组分反应，以高效收率合成了一系列邻苯二甲酰亚胺-铬烯和邻苯二甲酰亚胺-吡喃-2-酮杂化物。2H-吡喃-2-酮和丙二腈在室温下，在DABCO作为催化剂存在下通过Knoevenagel反应进行反应。化合物的特征在于1 H NMR和1313 C NMR，MS和FTIR。在Ellman分析中评估了由邻苯二甲酰亚胺-铬基/吡喃-2-酮部分和不同长度的间隔子束缚的所有化合物的生物活性。大多数化合物微弱地抑制了乙酰胆碱酯酶，对丁酰胆碱酯酶没有活性。
• Discovery of imidazopyridines containing isoindoline-1,3-dione framework as a new class of BACE1 inhibitors: Design, synthesis and SAR analysis
  作者：Sara Azimi、Afsaneh Zonouzi、Omidreza Firuzi、Aida Iraji、Mina Saeedi、Mohammad Mahdavi、Najmeh Edraki

  DOI：10.1016/j.ejmech.2017.06.040

  日期：2017.9

  Alzheimer's disease is characterized by chronic neurodegeneration leading to dementia. The main cause of neurodegeneration is considered to be the accumulation of amyloid-beta. Inhibiting BACE1 is a well studied approach to lower the burden of amyloid-beta aggregates. We designed a series of imidazopyridines-based compounds bearing phthalimide moieties as inhibitors of BACE1. The compounds 8a-o were synthesized by the Groebke Blackburn Bienayme three-component reaction of heteroaromatic amidines, aldehydes and isocyanides. Evaluating the BACE1 inhibitory effects of the synthesized compounds revealed that introducing an aminocyclohexyl moiety in the imidazopyridine core resulted in a significant improvement in its BACE1 inhibitory potential. In this regard, compound 8e was the most potent against BACE1 with an IC50 value of 2.84 (+/- 0.95) mu M. Molecular docking revealed that the nitrogen atom of imidazopyridines and the oxygen atom of the phenoxypropyl linker were involved in hydrogen bound interactions with Asp228 and Asp32 of BACE1 active site, respectively. The phthalimide moiety oriented toward the flap pocket and interacted with phe108, 11e110, Trp115, 11e118 through van der Waal's and hydrophobic interactions. These findings demonstrate that imidazopyridines-based compounds bearing phthalimide moiety have the potential to decrease amyloid-beta levels and ameliorate the symptoms of Alzheimer's disease. (C) 2017 Published by Elsevier Masson SAS.
• Design, synthesis and biological evaluation of novel phthalimide-Schiff base-coumarin hybrids as potent α-glucosidase inhibitors
  作者：Maedeh Sherafati、Maryam Mohammadi-Khanaposhtani、Shahram Moradi、Mohammad Sadegh Asgari、Nadia Najafabadipour、Mohammad Ali Faramarzi、Mohammad Mahdavi、Mahmood Biglar、Bagher Larijani、Haleh Hamedifar、Mir Hamed Hajimiri

  DOI：10.1007/s11696-020-01246-7

  日期：2020.12

  We have designed and synthesized phthalimide-Schiff base-coumarin hybrids 8a–b, 9a–d, 10a–b, and 11a–d and evaluated them for α-glucosidase inhibitory potential against yeast form of this enzyme. For the synthesis of title compounds 4-hydroxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde, 2-hydroxybenzaldehyde, 2-hydroxybenzaldehyde derivatives, coumarin-3-carbohydrazide, and coumarin-7-yloxy-acetohydrazide

  我们设计并合成了邻苯二甲酰亚胺-席夫碱-香豆素杂种8a - b，9a - d，10a - b和11a - d，并评估了它们对这种酶的酵母形式的α-葡萄糖苷酶抑制潜力。为了合成标题化合物4-羟基苯甲醛，4-羟基-3-甲氧基苯甲醛，2-羟基苯甲醛，2-羟基苯甲醛衍生物，香豆素-3-碳酰肼和香豆素-7-酰氧基-乙酰肼。体外对α-葡萄糖苷酶的抑制作用表明，所有合成的化合物均对IC 50表现出出色的α-葡萄糖苷酶抑制作用与IC 50值为750.0±12.0 µM的标准抑制剂阿卡波糖相比，该值介于85.2±1.7至577.7±7.5 µM之间。最有效的化合物是带有香豆素-3-碳酰肼部分的4-羟基苯甲醛衍生物8a，带有香豆素-7-酰氧基-乙酰肼部分的2-羟基-5-硝基苯甲醛衍生物11d和带有香豆素-3-的2-羟基-5-硝基苯甲醛衍生物9d。 3-碳酰肼部分。进行了分子对接研究以了解最具活性的化合物与标准