6-<(3-aminopropyl)amino>hexanoic acid dihydrochloride | 142160-50-7

• 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: 6-<(3-aminopropyl)amino>hexanoic acid dihydrochloride
• 英文别名: 6-[(3-aminopropyl)amino]hexanoic acid dihydrochloride；6-(3-aminopropylamino)hexanoic acid;hydrochloride
• CAS: 142160-50-7
• 化学式: C₉H₂₀N₂O₂*2ClH
• 分子量: 261.192
• InChiKey: DLBJEPKZJUGCGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.99
• 重原子数：
  14.0
• 可旋转键数：
  9.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  75.35
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  ethyl 6-<<<3-(tert-butoxycarbonyl)amino>propyl>amino>hexanoate 在 盐酸 作用下， 反应 49.0h， 生成 6-<(3-aminopropyl)amino>hexanoic acid dihydrochloride
  参考文献：
  名称：

  Inhibition of N8-acetylspermidine deacetylase by active-site-directed metal coordinating inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm00091a009

文献信息

• 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。