(6-methoxycarbonyl-2-naphthyl)methyl 4-[2-[(2-chloroacetyl)amino]acetyl]piperazine-1-carboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (6-methoxycarbonyl-2-naphthyl)methyl 4-[2-[(2-chloroacetyl)amino]acetyl]piperazine-1-carboxylate
• 英文别名: (6-Methoxycarbonyl-2-naphthyl)methyl 4-[2-[(2-chloroacetyl)amino]acetyl]piperazine-1-carboxylate (6n)；(6-methoxycarbonylnaphthalen-2-yl)methyl 4-[2-[(2-chloroacetyl)amino]acetyl]piperazine-1-carboxylate
• 化学式: C₂₂H₂₄ClN₃O₆
• 分子量: 461.902
• InChiKey: XMHWYLIAMQVIAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-羟甲基-2-萘甲酸甲酯 在 N-甲基吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 62.0h， 生成 (6-methoxycarbonyl-2-naphthyl)methyl 4-[2-[(2-chloroacetyl)amino]acetyl]piperazine-1-carboxylate
  参考文献：
  名称：

  Development of Potent and Selective Tissue Transglutaminase Inhibitors: Their Effect on TG2 Function and Application in Pathological Conditions

  摘要：

  Potent-selective peptidomimetic inhibitors of tissue transglutaminase (TG2) were developed through a combination of protein-ligand docking and molecular dynamic techniques. Derivatives of these inhibitors were made with the aim of specific TG2 targeting to the intra-and extracellular space. A cell-permeable fluorescently labeled derivative enabled detection of in situ cellular TG2 activity in human umbilical cord endothelial cells and TG2-transduced NIH3T3 cells, which could be enhanced by treatment of cells with ionomycin. Reaction of TG2 with this fluorescent inhibitor in NIH3T3 cells resulted in loss of binding of TG2 to cell surface syndecan-4 and inhibition of translocation of the enzyme into the extracellular matrix, with a parallel reduction in fibronectin deposition. In human umbilical cord endothelial cells, this same fluorescent inhibitor also demonstrated a reduction in fibronectin deposition, cell motility, and cord formation in Matrigel. Use of the same inhibitor in a mouse model of hypertensive nephrosclerosis showed over a 40% reduction in collagen deposition.

  DOI：

  10.1016/j.chembiol.2015.08.013

文献信息

• [EN] ACYLPIPERAZINES AS INHIBITORS OF TRANSGLUTAMINASE AND THEIR USE IN MEDICINE<br/>[FR] ACYL-PIPERAZINES EN TANT QU'INHIBITEURS DE LA TRANSGLUTAMINASE ET LEUR UTILISATION EN MÉDECINE
  申请人：UNIV ASTON

  公开号：WO2014057266A1

  公开（公告）日：2014-04-17

  The present invention relates to novel compounds of Formula I capable of inhibiting tissue transglutaminase, and uses of the same in medicine. In particular, the invention provides compounds for use in the treatment of prevention of disease and conditions such as fibrosis (e.g. cystic fibrosis), scarring, neurodegenerative diseases (e.g. Alzheimer's disease, Huntington's disease and Parkinson's disease), autoimmune diseases (e.g. multiple sclerosis and coeliac disease), thrombosis, proliferative disorders (e.g. cancers), AIDS, psoriasis and inflammation (e.g. chronic inflammatory diseases).

  本发明涉及一种能够抑制组织转谷氨酰胺酶的化合物I式新化合物，以及在医学上的用途。具体而言，该发明提供了用于治疗或预防疾病和病况的化合物，如纤维化（例如囊性纤维化）、瘢痕形成、神经退行性疾病（例如阿尔茨海默病、亨廷顿病和帕金森病）、自身免疫疾病（例如多发性硬化症和乳糜泻）、血栓形成、增生性疾病（例如癌症）、艾滋病、银屑病和炎症（例如慢性炎症性疾病）的化合物。
• Acylpiperazines as Inhibitors of Transglutaminase and Their Use in Medicine
  申请人：ASTON UNIVERSITY

  公开号：US20150259310A1

  公开（公告）日：2015-09-17

  The present invention relates to novel compounds of Formula I capable of inhibiting tissue transglutaminase, and uses of the same in medicine. In particular, the invention provides compounds for use in the treatment of prevention of disease and conditions such as fibrosis (e.g. cystic fibrosis), scarring, neurodegenerative diseases (e.g. Alzheimer's disease, Huntington's disease and Parkinson's disease), autoimmune diseases (e.g. multiple sclerosis and coeliac disease), thrombosis, proliferative disorders (e.g. cancers), AIDS, psoriasis and inflammation (e.g. chronic inflammatory diseases).

  本发明涉及一种能够抑制组织转谷氨酰胺酶的新型化合物I，以及在医学上使用它们的方法。特别地，本发明提供了用于治疗和预防疾病和病况（如纤维化（例如囊性纤维化），瘢痕，神经退行性疾病（例如阿尔茨海默病，亨廷顿病和帕金森病），自身免疫性疾病（例如多发性硬化症和乳糜泻），血栓形成，增生性疾病（例如癌症），艾滋病，牛皮癣和炎症（例如慢性炎症性疾病））的化合物。
• ACYLPIPERAZINES AS INHIBITORS OF TRANSGLUTAMINASE AND THEIR USE IN MEDICINE
  申请人：Aston University

  公开号：EP2906543B1

  公开（公告）日：2019-01-02
• US9656978B2
  申请人：——

  公开号：US9656978B2

  公开（公告）日：2017-05-23
• Development of Potent and Selective Tissue Transglutaminase Inhibitors: Their Effect on TG2 Function and Application in Pathological Conditions
  作者：Eduard Badarau、Zhuo Wang、Dan L. Rathbone、Andrea Costanzi、Thomas Thibault、Colin E. Murdoch、Said El Alaoui、Milda Bartkeviciute、Martin Griffin

  DOI：10.1016/j.chembiol.2015.08.013

  日期：2015.10

  Potent-selective peptidomimetic inhibitors of tissue transglutaminase (TG2) were developed through a combination of protein-ligand docking and molecular dynamic techniques. Derivatives of these inhibitors were made with the aim of specific TG2 targeting to the intra-and extracellular space. A cell-permeable fluorescently labeled derivative enabled detection of in situ cellular TG2 activity in human umbilical cord endothelial cells and TG2-transduced NIH3T3 cells, which could be enhanced by treatment of cells with ionomycin. Reaction of TG2 with this fluorescent inhibitor in NIH3T3 cells resulted in loss of binding of TG2 to cell surface syndecan-4 and inhibition of translocation of the enzyme into the extracellular matrix, with a parallel reduction in fibronectin deposition. In human umbilical cord endothelial cells, this same fluorescent inhibitor also demonstrated a reduction in fibronectin deposition, cell motility, and cord formation in Matrigel. Use of the same inhibitor in a mouse model of hypertensive nephrosclerosis showed over a 40% reduction in collagen deposition.