4-Chloro-3-(2-methoxy-ethoxy)-7-nitro-isocoumarin | 360774-10-3

• 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
• 英文名称: 4-Chloro-3-(2-methoxy-ethoxy)-7-nitro-isocoumarin
• 英文别名: 4-chloro-3-(2-methoxyethoxy)-7-nitroisochromen-1-one
• CAS: 360774-10-3
• 化学式: C₁₂H₁₀ClNO₆
• 分子量: 299.668
• InChiKey: DIZWRSCHLRZXOA-UHFFFAOYSA-N

物化性质

• 熔点：
  127 °C
• 沸点：
  483.7±45.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 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：
  90.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-Chloro-3-(2-methoxy-ethoxy)-7-nitro-isocoumarin 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以100%的产率得到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
• 作为产物：
  描述：

  2-乙酸基-4-硝基苯甲酸 在 五氯化磷 、 硫酸 作用下， 以 甲苯 为溶剂， 反应 15.12h， 生成 4-Chloro-3-(2-methoxy-ethoxy)-7-nitro-isocoumarin
  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

• [EN] ISOCOUMARIN INHIBITING PRODUCTION OF AMYLOID PEPTIDE, PREPARATION, COMPOSITIONS CONTAINING SAME AND USES<br/>[FR] ISOCOUMARINES INHIBITRICES DE LA PRODUCTION DE PEPTIDE AMYLOIDE, PREPARATION, COMPOSITIONS LES CONTENANT ET UTILISATIONS
  申请人：TROPHOS

  公开号：WO2002048102A2

  公开（公告）日：2002-06-20

  La présente invention concerne de nouveaux composés inhibiteurs de la production de peptide amyloïde, leur préparation et leurs utilisations. Elle concerne également des procédés pour l'identification ou la caractérisation de composés inhibiteurs de la production de peptide amyloide, en particulier inhibiteurs sélectifs de la production de peptide amyloïde (et notamment non toxiques pour le développement embryonnaire). L'invention est également relative à des méthodes et utilisations des composés pour le traitement de désordres du système nerveux, en particulier de pathologies neurodégénératives telles la maladie d'Alzheimer.
• 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
  作者：Frédéric Bihel、Gilles Quéléver、Hugues Lelouard、Agnès Petit、Cristine Alvès da Costa、Olivier Pourquié、Frédéric Checler、Annie Thellend、Philippe Pierre、Jean-Louis Kraus

  DOI：10.1016/s0968-0896(03)00235-9

  日期：2003.7

  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.