N-(1-Adamantylcarbonyl)-piperazin | 29869-08-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-(1-Adamantylcarbonyl)-piperazin
• 英文别名: 1-(adamantane-1-carbonyl)-piperazine；1-(1-adamantanecarbonyl)piperazine；1-(1-Adamantylcarbonyl)piperazine；1-adamantyl(piperazin-1-yl)methanone
• CAS: 29869-08-7
• 化学式: C₁₅H₂₄N₂O
• mdl: MFCD09787917
• 分子量: 248.368
• InChiKey: XAFSAELWLMDLKL-UHFFFAOYSA-N

物化性质

• 沸点：
  407.7±38.0 °C(Predicted)
• 密度：
  1.154±0.06 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：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.933
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  N-(1-Adamantylcarbonyl)-piperazin 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 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 36.0h， 生成 1-[4-(adamantane-1-carbonyl)piperazin-1-yl]-2-aminoethanone
  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
• 作为产物：
  描述：

  金刚烷 在 N-甲基吗啉 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 N-(1-Adamantylcarbonyl)-piperazin
  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

• Antihypertensive quinazoline compounds
  申请人：Sumitomo Chemical Company, Limited

  公开号：US04230706A1

  公开（公告）日：1980-10-28

  Quinazoline compounds of the formula: ##STR1## wherein A is ##STR2## wherein n is an integer of 1 or 2, or ##STR3## wherein X is O or CH.sub.2, and n and m are independently an integer of 1 or 2, and its non-toxic pharmaceutically acceptable salts, having an excellent antihypertensive activity without causing adverse effects such as orthostatic hypotension.

  公式为：##STR1## 其中 A 为 ##STR2## 其中 n 为1或2的整数，或 ##STR3## 其中 X 为 O 或 CH.sub.2，n 和 m 分别为1或2的整数，及其非毒性的药学上可接受的盐，具有优异的抗高血压活性，不会引起直立性低血压等不良反应。
• Discovery and Structure–Activity Relationship of Potent and Selective Covalent Inhibitors of Transglutaminase 2 for Huntington’s Disease
  作者：Michael E. Prime、Ole A. Andersen、John J. Barker、Mark A. Brooks、Robert K. Y. Cheng、Ian Toogood-Johnson、Stephen M. Courtney、Frederick A. Brookfield、Christopher J. Yarnold、Richard W. Marston、Peter D. Johnson、Siw F. Johnsen、Jordan J. Palfrey、Darshan Vaidya、Sayeh Erfan、Osamu Ichihara、Brunella Felicetti、Shilpa Palan、Anna Pedret-Dunn、Sabine Schaertl、Ina Sternberger、Andreas Ebneth、Andreas Scheel、Dirk Winkler、Leticia Toledo-Sherman、Maria Beconi、Douglas Macdonald、Ignacio Muñoz-Sanjuan、Celia Dominguez、John Wityak

  DOI：10.1021/jm201310y

  日期：2012.2.9

  Tissue transglutaminase 2 (TG2) is a multifunctional protein primarily known for its calcium-dependent enzymatic protein cross-linking activity via isopeptide bond formation between glutamine and lysine residues. TG2 overexpression and activity have been found to be associated with Huntington's disease (HD); specifically, TG2 is up-regulated in the brains of HD patients and in animal models of the disease. Interestingly, genetic deletion of TG2 in two different HD mouse models, R6/1 and R6/2, results in improved phenotypes including a reduction in neuronal death and prolonged survival. Starting with phenylacrylamide screening hit 7d, we describe the SAR of this series leading to potent and selective TG2 inhibitors. The suitability of the compounds as in vitro tools to elucidate the biology of TG2 was demonstrated through mode of inhibition studies, characterization of druglike properties, and inhibition profiles in a cell lysate assay.
• Discovery and biological evaluation of adamantyl amide 11β-HSD1 inhibitors
  作者：Scott P. Webster、Peter Ward、Margaret Binnie、Eilidh Craigie、Kirsty M.M. McConnell、Karen Sooy、Andy Vinter、Jonathan R. Seckl、Brian R. Walker

  DOI：10.1016/j.bmcl.2007.02.057

  日期：2007.5

  A series of adamantyl amide 11 beta-HSD1 inhibitors has been discovered and chemically modified. Selected compounds are selective for 11 beta-HSD1 over 11 beta-HSD2 and possess excellent cellular potency in human and murine 11 beta-HSD1 assays. Good pharmacodynamic characteristics are observed in ex vivo assays. (c) 2007 Elsevier Ltd. All rights reserved.
• 4-Amino-6,7-dimethoxy quinazoline derivatives, process for their preparation, their use and a pharmaceutical composition
  申请人：SUMITOMO CHEMICAL COMPANY, LIMITED

  公开号：EP0004389B1

  公开（公告）日：1982-04-07
• INHIBITORS OF PRENYL-PROTEIN TRANSFERASE
  申请人：Merck & Co., Inc.

  公开号：EP1165013A2

  公开（公告）日：2002-01-02