N,N'-bis(tert-butoxycarbonyl)-6-<(3-aminopropyl)amino>hexanoic acid | 142160-53-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N,N'-bis(tert-butoxycarbonyl)-6-<(3-aminopropyl)amino>hexanoic acid
• 英文别名: N,N'-bis(tert-butoxycarbonyl)-6-[(3-aminopropyl)amino]hexanoic acid；6-[(2-Methylpropan-2-yl)oxycarbonyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]hexanoic acid
• CAS: 142160-53-0
• 化学式: C₁₉H₃₆N₂O₆
• 分子量: 388.505
• InChiKey: BLEHYTLTQVUWLP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N,N'-bis(tert-butoxycarbonyl)-6-<(3-aminopropyl)amino>hexanoic acid 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 N,N'-bis(tert-butoxycarbonyl)-7-[(3-aminopropyl)amino]heptan-2-one
  参考文献：
  名称：

  N8-乙酰亚精胺类似物作为细菌乙酰多胺酰胺水解酶抑制剂的合成与评价

  摘要：

  聚胺是许多生物过程中涉及的小的必需聚阳离子。多胺代谢酶已被广泛研究并且是有吸引力的药物靶点。然而，多胺的可逆乙酰化仍然知之甚少。尽管已经检测和研究了真核N 8 -乙酰亚精胺脱乙酰酶活性，但尚未确定负责该活性的特定酶。然而，来自支原体的锌脱乙酰酶据报道，乙酰多胺酰胺水解酶 (APAH) 使用各种乙酰多胺作为底物。最近解决的这种聚胺脱乙酰酶的晶体结构揭示了在二聚体界面形成了一个“L”形活性位点隧道，具有理想的尺寸和静电特性，可容纳狭窄、灵活的阳离子聚胺底物。在这里，我们报告了带有不同锌结合基团的N 8 -乙酰亚精胺类似物作为 APAH 潜在抑制剂的设计、合成和评估。大多数合成的化合物表现出适度的效力，IC 50值在中微摩尔范围内，但带有异羟肟酸酯或三氟甲基酮锌结合基团的化合物在中纳摩尔范围内表现出增强的抑制效力。这些抑制剂将使未来对原核生物和真核生物中乙酰多胺功能的探索成为可能。

  DOI：

  10.1016/j.bmc.2013.05.045
• 作为产物：
  描述：

  6-氯-1-己醇 在 重铬酸吡啶 、 potassium carbonate 、 potassium iodide 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 30.0h， 生成 N,N'-bis(tert-butoxycarbonyl)-6-<(3-aminopropyl)amino>hexanoic acid
  参考文献：
  名称：

  Structure−Immunosuppressive Activity Relationships of New Analogues of 15-Deoxyspergualin. 1. Structural Modifications of the Hydroxyglycine Moiety

  摘要：

  A series of new analogues of 15-deoxyspergualin (DSG), an immunosuppressive agent currently commercialized in Japan, was synthesized and tested in a graft-versus-host disease (GVHD) model in mice. Using the general concept of bioisosteric replacement, variations of the hydroxyglycine central "C" region were made in order to determine its optimum structure in terms of in vivo immunosuppressive activity. By this way, the malonic derivative 13a was discovered as the first example of a new series of potent immunosuppressive agents encompassing a retro-amide bond linked to the hexyl-guanidino moiety. Structure-activity relationships of this series were studied by synthesizing compounds 13g-i and 13k-s. Variation of the "right-amide" of 13a led to the urea 19a and the carbamates 23 and 27a which proved to be equally active as DSG in our GVHD model. Finally 27a was found to be the most potent derivative, being slightly more active than DSG in a heart allotransplantation model in rats. Due to the absence of chiral center in its structure and to its improved chemical stability compared to DSG, 27a was selected as a candidate for clinical evaluation.

  DOI：

  10.1021/jm980431g

文献信息

• [EN] FUNCTIONAL LIPID DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS LIPIDIQUES FONCTIONNELS ET LEURS UTILISATIONS
  申请人：OHIO STATE INNOVATION FOUNDATION

  公开号：WO2021237055A1

  公开（公告）日：2021-11-25

  The present disclosure relates to compounds, compositions, and methods for delivery of therapeutic, diagnostic, or prophylactic agents (for example, a nucleic acid).

  本公开涉及化合物、组合物和用于传递治疗、诊断或预防性药剂（例如核酸）的方法。
• Inhibition of N8-acetylspermidine deacetylase by active-site-directed metal coordinating inhibitors
  作者：Tien L. Huang、Sasi A. Dredar、Victor A. Manneh、James W. Blankenship、David S. Fries

  DOI：10.1021/jm00091a009

  日期：1992.6

  A number of substrate analogues of N8-acetylspermidine (N8-AcSpd) (16) and chemical modifying agents containing metal coordinating ligands were assayed as inhibitors of the cytoplasmic enzyme N8-AcSpd deacetylase from rat liver. The enzyme is inhibited by metal chelators, several omega-amino-substituted carboxylic acids, and some thiol reagents. Inhibition by diisopropyl fluorophosphate was observed only at high concentrations. These results suggest that the catalytic mechanism of the enzyme requires a transition state metal and free sulfhydryl groups for activity. The most potent inhibitor synthesized 6-[(3-aminopropyl)amino]-N-hydroxyhexanamide (15), has an apparent K(i) of 0.001-mu-M. It binds to the target enzyme 11 000 times tighter than the substrate (apparent K(m) = 11-mu-M). These compounds and a previously reported series of compounds (Dredar, S. A.; Blankenship, J. W.; Marchant, P. E.; Manneh, V. A.; Fries, D. S. J. Med. Chem. 1989, 32, 984-989) are useful in mapping the active site and determining the physiological function of N8-AcSpd deacetylase.
• Structure−Immunosuppressive Activity Relationships of New Analogues of 15-Deoxyspergualin. 1. Structural Modifications of the Hydroxyglycine Moiety
  作者：Luc Lebreton、Jocelyne Annat、Philippe Derrepas、Patrick Dutartre、Patrice Renaut

  DOI：10.1021/jm980431g

  日期：1999.1.1

  A series of new analogues of 15-deoxyspergualin (DSG), an immunosuppressive agent currently commercialized in Japan, was synthesized and tested in a graft-versus-host disease (GVHD) model in mice. Using the general concept of bioisosteric replacement, variations of the hydroxyglycine central "C" region were made in order to determine its optimum structure in terms of in vivo immunosuppressive activity. By this way, the malonic derivative 13a was discovered as the first example of a new series of potent immunosuppressive agents encompassing a retro-amide bond linked to the hexyl-guanidino moiety. Structure-activity relationships of this series were studied by synthesizing compounds 13g-i and 13k-s. Variation of the "right-amide" of 13a led to the urea 19a and the carbamates 23 and 27a which proved to be equally active as DSG in our GVHD model. Finally 27a was found to be the most potent derivative, being slightly more active than DSG in a heart allotransplantation model in rats. Due to the absence of chiral center in its structure and to its improved chemical stability compared to DSG, 27a was selected as a candidate for clinical evaluation.
• Synthesis and evaluation of N8-acetylspermidine analogues as inhibitors of bacterial acetylpolyamine amidohydrolase
  作者：Christophe Decroos、Christine M. Bowman、David W. Christianson

  DOI：10.1016/j.bmc.2013.05.045

  日期：2013.8

  Polyamines are small essential polycations involved in many biological processes. Enzymes of polyamine metabolism have been extensively studied and are attractive drug targets. Nevertheless, the reversible acetylation of polyamines remains poorly understood. Although eukaryotic N8-acetylspermidine deacetylase activity has already been detected and studied, the specific enzyme responsible for this activity

  聚胺是许多生物过程中涉及的小的必需聚阳离子。多胺代谢酶已被广泛研究并且是有吸引力的药物靶点。然而，多胺的可逆乙酰化仍然知之甚少。尽管已经检测和研究了真核N 8 -乙酰亚精胺脱乙酰酶活性，但尚未确定负责该活性的特定酶。然而，来自支原体的锌脱乙酰酶据报道，乙酰多胺酰胺水解酶 (APAH) 使用各种乙酰多胺作为底物。最近解决的这种聚胺脱乙酰酶的晶体结构揭示了在二聚体界面形成了一个“L”形活性位点隧道，具有理想的尺寸和静电特性，可容纳狭窄、灵活的阳离子聚胺底物。在这里，我们报告了带有不同锌结合基团的N 8 -乙酰亚精胺类似物作为 APAH 潜在抑制剂的设计、合成和评估。大多数合成的化合物表现出适度的效力，IC 50值在中微摩尔范围内，但带有异羟肟酸酯或三氟甲基酮锌结合基团的化合物在中纳摩尔范围内表现出增强的抑制效力。这些抑制剂将使未来对原核生物和真核生物中乙酰多胺功能的探索成为可能。