4-chloro-3-methoxy-7-nitroisocoumarin | 62252-25-9

• 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-methoxy-7-nitroisocoumarin
• 英文别名: 7-nitro-4-chloro-3-methoxyisocoumarin；4-Chlor-3-methoxy-7-nitroisocumarin；7-nitro-3-methoxy-4-chloroisocoumarin；4-Chloro-3-methoxy-7-nitro-isocoumarin；4-chloro-3-methoxy-7-nitroisochromen-1-one
• CAS: 62252-25-9
• 化学式: C₁₀H₆ClNO₅
• 分子量: 255.614
• InChiKey: XZLVSPYCCQKAAX-UHFFFAOYSA-N

物化性质

• 熔点：
  115 °C
• 沸点：
  455.1±45.0 °C(Predicted)
• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  81.4
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  4-chloro-3-methoxy-7-nitroisocoumarin 在 palladium on activated charcoal 、 氢气 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 以87%的产率得到7-氨基-4-氯-3-甲氧基异香豆素
  参考文献：
  名称：

  异香豆素的炔烃衍生物作为丝氨酸蛋白酶的可点击的基于活性的探针

  摘要：

  基于活动的探针（ABP）已发现在功能蛋白质组学研究中的使用越来越多。近来，可与点击化学结合使用的ABP由于其在体内和体外的灵活应用而受到了特别的关注。此外，持续需要针对小部分酶的新ABP。我们在此报告基于4-氯-异香豆素（IC）亲电子体的新型可点击ABP，这是一种基于机理的抑制剂骨架，与丝氨酸蛋白酶共价结合。我们描述了一个IC ABPs小库的合成，该库包含炔烃功能和一组不同的选择性元素。IC结构上的不同取代基决定结合哪些蛋白酶，与优选的底物偏好表现出良好的相关性。IC ABP可以以敏感的方式（低至总蛋白的0.007％）在蛋白质组背景中检测其目标蛋白酶。此外，我们显示了组织蛋白质组中内源蛋白酶的活性依赖性和选择性标记。因此，这些IC代表了对丝氨酸蛋白酶已经存在的ABP的宝贵扩展，并且可能在将来阐明丝氨酸蛋白酶功能方面发挥了作用。

  DOI：

  10.1016/j.bmc.2011.03.014
• 作为产物：
  描述：

  2-(2-methoxy-2-oxoethyl)-5-nitrobenzoic acid 在 五氯化磷 作用下， 以 甲苯 为溶剂， 以51%的产率得到4-chloro-3-methoxy-7-nitroisocoumarin
  参考文献：
  名称：

  异香豆素的炔烃衍生物作为丝氨酸蛋白酶的可点击的基于活性的探针

  摘要：

  基于活动的探针（ABP）已发现在功能蛋白质组学研究中的使用越来越多。近来，可与点击化学结合使用的ABP由于其在体内和体外的灵活应用而受到了特别的关注。此外，持续需要针对小部分酶的新ABP。我们在此报告基于4-氯-异香豆素（IC）亲电子体的新型可点击ABP，这是一种基于机理的抑制剂骨架，与丝氨酸蛋白酶共价结合。我们描述了一个IC ABPs小库的合成，该库包含炔烃功能和一组不同的选择性元素。IC结构上的不同取代基决定结合哪些蛋白酶，与优选的底物偏好表现出良好的相关性。IC ABP可以以敏感的方式（低至总蛋白的0.007％）在蛋白质组背景中检测其目标蛋白酶。此外，我们显示了组织蛋白质组中内源蛋白酶的活性依赖性和选择性标记。因此，这些IC代表了对丝氨酸蛋白酶已经存在的ABP的宝贵扩展，并且可能在将来阐明丝氨酸蛋白酶功能方面发挥了作用。

  DOI：

  10.1016/j.bmc.2011.03.014

文献信息

• Effect of the 7-amino substituent on the inhibitory potency of mechanism-based isocoumarin inhibitors for porcine pancreatic and human neutrophil elastases: a 1.85-.ANG. x-ray structure of the complex between porcine pancreatic elastase and 7-[(N-tosylphenylalanyl)amino]-4-chloro-3-methoxyisocoumarin
  作者：Maria A. Hernandez、James C. Powers、Jan Glinski、Jozef Oleksyszyn、J. Vijayalakshmi、Edgar F. Meyer

  DOI：10.1021/jm00084a018

  日期：1992.3

  A series of new acyl, urea, and carbonate derivatives of 7-amino-4-chloro-3-methoxyisocoumarin were synthesized and evaluated as irreversible inhibitors of human neutrophil elastase (HNE) and porcine pancreatic elastase (PPE). Inhibition of HNE is directly related to the hydrophobicity of the substituent on the 7-amino group. The N-Tos-Phe derivative (19) is the best HNE inhibitor with a second-order

  合成了一系列新的7-氨基-4-氯-3-甲氧基异香豆素的酰基，脲和碳酸酯衍生物，并作为人嗜中性弹性蛋白酶（HNE）和猪胰弹性蛋白酶（PPE）的不可逆抑制剂进行了评估。HNE的抑制与7-氨基上取代基的疏水性直接相关。N-Tos-Phe衍生物（19）是最好的HNE抑制剂，其二级速率常数kobs / [I] = 200,000 M-1 s-1。该系列中最接近的类似物3,3-二苯基丙酰基衍生物5具有HNE的kobs / [I] = 130,000 M-1 s-1。与Tos-Phe衍生物19相比，苯乙酰基衍生物2和碳酸盐22和25提供了极其稳定的酶-抑制剂复合物，两种弹性蛋白酶的脱酰化半衰期均长于48小时。N-苯基脲衍生物25是PPE的最佳抑制剂，其二级速率常数kobs / [I] = 7300 M-1 s-1。以1.85-A的分辨率测定了PPE与N-甲苯磺酰基-Phe衍生物19的配合物的晶体结构，并将其精制为最终的R因子为16
• 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.
• Isocoumarin-based inhibitors of pancreatic cholesterol esterase
  作者：Justin J. Heynekamp、Lucy A. Hunsaker、Thomas A. Vander Jagt、Robert E. Royer、Lorraine M. Deck、David L. Vander Jagt

  DOI：10.1016/j.bmc.2008.03.016

  日期：2008.5

  Pancreatic cholesterol esterase (CEase), which is secreted from the exocrine pancreas, is a serine hydrolase that aids in the bile salt-dependent hydrolysis of dietary cholesteryl esters and contributes to the hydrolysis of triglycerides and phospholipids. Additional roles for CEase in intestinal micelle formation and in transport of free cholesterol to the enterocyte have been suggested. There also are studies that point to a pathological role(s) for CEase in the circulation where CEase accumulates in atherosclerotic lesions and triggers proliferation of smooth muscle cells. Thus, there is interest in CEase as a potential drug target. 4-Chloro-3-alkoxyisocoumarins are a class of haloenol lactones that inhibit serine hydrolases and serine proteases and have the potential to be suicide inhibitors. In the present study, we have developed 3-alkoxychloroisocoumarins that are potent inhibitors of CEase. These inhibitors were designed to have a saturated cycloalkane ring incorporated into a 3-alkoxy substituent. The size of the ring as well as the length of the tether holding the ring was found to be important contributors to binding to CEase. 4-Chloro-3-(4-cyclohexylbutoxy) isocoumarin and 4-chloro-3-(3-cyclopentylpropoxy) isocoumarin were demonstrated to be potent reversible inhibitors of CEase, with dissociation constants of 11 nM and 19 nM, respectively. The kinetic results are consistent with predictions from molecular modeling. (C) 2008 Elsevier Ltd. All rights reserved.
• CHOKSEY I.; USGAONKAR R. N., INDIAN J. CHEM. <IJOC-AP>, 1976, B 14, NO 8, 596-598
  作者：CHOKSEY I.、 USGAONKAR R. N.

  DOI：——

  日期：——
• US4596822A
  申请人：——

  公开号：US4596822A

  公开（公告）日：1986-06-24