7-氨基-4-氯-3-(2-甲氧基乙氧基)异色烯-1-酮 | 126062-23-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异香豆素及其衍生物
• 中文名称: 7-氨基-4-氯-3-(2-甲氧基乙氧基)异色烯-1-酮
• 英文名称: JLK 2
• 英文别名: 7-Amino-4-chloro-3-(2-methoxy-ethoxy)-isocoumarin；7-amino-4-chloro-3-(2-methoxyethoxy)isochromen-1-one
• CAS: 126062-23-5
• 化学式: C₁₂H₁₂ClNO₄
• 分子量: 269.685
• InChiKey: OMXCGKFGFJFIOP-UHFFFAOYSA-N

物化性质

• 熔点：
  127 °C
• 沸点：
  482.6±45.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  70.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-金刚烷基氟甲酸 、 7-氨基-4-氯-3-(2-甲氧基乙氧基)异色烯-1-酮 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 72.0h， 以50%的产率得到[4-chloro-3-(2-methoxy-ethoxy)-1-oxo-1H-isochromen-7-yl]-carbamic acid adamantan-1-yl ester
  参考文献：
  名称：

  Synthesis of new 3-alkoxy-7-amino-4-chloro-isocoumarin derivatives as new β-amyloid peptide production inhibitors and their activities on various classes of protease

  摘要：

  A series of new 7-substituted-4-chloro-3-alkoxy isocoumarin derivatives were synthesized and evaluated as inhibitors of representative classes of proteases: serine protease (alpha-chymotrypsin, trypsin), cysteine protease (Caspase-3), and aspartyl protease (HIV-protease), 20S proteasome and also as inhibitors of amyloid peptide gamma-secretase-mediated production. Protease inhibition selectivity is directly related to the structure of the substituent at the 7-position of the isocoumarin nucleus. 7-Nitro-isocoumarin derivatives (4c, 4d 4f) are potent alpha-chymotrypsin inhibitors but slightly active or inactive on HIV-protease, as well as on cysteine protease. In contrast.. only derivatives bearing a free amino (5d, 5f) or a substituted amino group (6f) at the 7-position of the isocoumarin nucleus, were found weakly active or inactive on alpha-chymotrypsin, trypsin, Caspase-3 and HIV-protease, but prevent gamma-secretase-mediated production of Abeta 40/42 amyloid peptides, which is known to be involved in Alzheimer's disease. Moreover, the most active compounds on beta-amyloid peptide production [JLK6 (5d), JLK2 (5f) and JLK7 (6f)] show only weak or moderate inhibitory activity on the 20S proteasome. The obtained results suggest that the described new isocoumarin analogues could be of interest, since compounds like JLK6 (5d), JLK2 (5f) and JLK7 (6f) can be considered as possible hits for the development of new agents directed towards Alzheimer's disease. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00235-9
• 作为产物：
  描述：

  2-乙酸基-4-硝基苯甲酸 在 palladium on activated charcoal 五氯化磷 、 硫酸 、 氢气 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 21.12h， 生成 7-氨基-4-氯-3-(2-甲氧基乙氧基)异色烯-1-酮
  参考文献：
  名称：

  Synthesis of new 3-alkoxy-7-amino-4-chloro-isocoumarin derivatives as new β-amyloid peptide production inhibitors and their activities on various classes of protease

  摘要：

  A series of new 7-substituted-4-chloro-3-alkoxy isocoumarin derivatives were synthesized and evaluated as inhibitors of representative classes of proteases: serine protease (alpha-chymotrypsin, trypsin), cysteine protease (Caspase-3), and aspartyl protease (HIV-protease), 20S proteasome and also as inhibitors of amyloid peptide gamma-secretase-mediated production. Protease inhibition selectivity is directly related to the structure of the substituent at the 7-position of the isocoumarin nucleus. 7-Nitro-isocoumarin derivatives (4c, 4d 4f) are potent alpha-chymotrypsin inhibitors but slightly active or inactive on HIV-protease, as well as on cysteine protease. In contrast.. only derivatives bearing a free amino (5d, 5f) or a substituted amino group (6f) at the 7-position of the isocoumarin nucleus, were found weakly active or inactive on alpha-chymotrypsin, trypsin, Caspase-3 and HIV-protease, but prevent gamma-secretase-mediated production of Abeta 40/42 amyloid peptides, which is known to be involved in Alzheimer's disease. Moreover, the most active compounds on beta-amyloid peptide production [JLK6 (5d), JLK2 (5f) and JLK7 (6f)] show only weak or moderate inhibitory activity on the 20S proteasome. The obtained results suggest that the described new isocoumarin analogues could be of interest, since compounds like JLK6 (5d), JLK2 (5f) and JLK7 (6f) can be considered as possible hits for the development of new agents directed towards Alzheimer's disease. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00235-9

文献信息

• Reactivity studies of 3-alkoxy-7-amino-4-chloroisocoumarins (β-amyloid peptide inhibitors)versus different classes of amines
  作者：Frédéric Bihel、Robert Faure、Jean-Louis Kraus

  DOI：10.1039/b209733h

  日期：——

  3-Alkoxy-7-amino-4-chloroisocoumarins have been shown to lower the β-amyloid secretion (a major component of the senile plaques involved in Alzheimer's disease). This paper reports the characterization of new adducts resulting from the reaction between the isocoumarin synthon and different classes of amines. This study allows on the one hand, a better understanding of the biological molecular processes by which such isocoumarin derivatives may interact with enzyme nucleophiles and, on the other hand, brings out the chemical potential of these synthons to generate new polycyclic derivatives.

  3-烷氧基-7-氨基-4-氯异香豆素已被证明可以降低δ-淀粉样蛋白的分泌（阿尔茨海默病老年斑的主要成分）。本文报告了异香豆素合成物与不同类别胺反应产生的新加合物的特征。通过这项研究，一方面可以更好地了解这些异香豆素衍生物与酶亲核物相互作用的生物分子过程，另一方面也可以发现这些合成物生成新的多环衍生物的化学潜力。
• N-Acyl substituted 7-amino-4-chloroisocoumarin: A peptide degradation model via an imide mechanism
  作者：Cédrik Garino、Frédéric Bihel、Florence Souard、Gilles Quéléver、Jean-Louis Kraus

  DOI：10.1016/j.bmcl.2004.01.030

  日期：2004.4

  During the coupling reaction between 3-alkoxy-7-amino-4-chloroisocoumarin and N-acyl alanine dipeptide, an unexpected deamidation reaction was observed. The proposed mechanism for this reaction involved the formation of an imide intermediate which after cleavage led to the release of amino acid moiety. The described deamidation reaction represents the first chemical model involving a non-peptidic moiety, which mimics biological and chemical deamidation processes occurring in proteins or peptides incorporating an asparagine or a glutamine residue. (C) 2004 Elsevier Ltd. All rights reserved.
• Blockade of gamma-secretase activity to promote myelination by oligodendrocytes
  申请人：Watkins Trent Alan

  公开号：US20110251133A1

  公开（公告）日：2011-10-13

  Methods are provided for enhancing myelination. Myelination is enhanced by administration of agents that are inhibitors of γ-secretase. Methods of screening for pharmaceutically active compounds that enhance myelination, and for genes involved in myelination are also provided.
• US5089633A
  申请人：——

  公开号：US5089633A

  公开（公告）日：1992-02-18
• US5324648A
  申请人：——

  公开号：US5324648A

  公开（公告）日：1994-06-28