6-((tert-butoxycarbonyl)amino)hexanoic (ethyl carbonic) anhydride | 219117-92-7

• 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-((tert-butoxycarbonyl)amino)hexanoic (ethyl carbonic) anhydride
• CAS: 219117-92-7
• 化学式: C₁₄H₂₅NO₆
• 分子量: 303.356
• InChiKey: VDGANVNWLMQQRY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.77
• 重原子数：
  21.0
• 可旋转键数：
  7.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  90.93
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  6-((tert-butoxycarbonyl)amino)hexanoic (ethyl carbonic) anhydride 在 palladium on activated charcoal 氢气 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 20.0 ℃ 、103.42 kPa 条件下， 反应 0.75h， 生成 N1-(tert-butoxycarbonyl)-6-oxo-7-aza-1,15-pentadecanediamine
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Symmetrically and Unsymmetrically Substituted Methoctramine-Related Polyamines as Muscular Nicotinic Receptor Noncompetitive Antagonists

  摘要：

  The universal template approach to drug design foresees that a polyamine can be modified in such a way to recognize any neurotransmitter receptor. Thus, hybrids of polymethylene tetraamines and philanthotoxins, exemplified by methoctramine (1) and PhTX-343 (2), respectively, were synthesized to produce novel inhibitors of muscular nicotinic acetylcholine receptors. Polyamines 3-25 were synthesized and their biological profiles were evaluated at frog rectus abdominis muscle nicotinic receptors and guinea pig left atria (M-2) and ileum longitudinal muscle (M-3) muscarinic acetylcholine receptors. All of the compounds, like prototypes 1 and 2, were noncompetitive antagonists of nicotinic receptors while being, like 1, competitive antagonists at,muscarinic M-2 and M-3 receptor subtypes. interestingly, polyamines bearing a low number of methylenes between the nitrogen atoms, as in 3, 6, and 7, displayed a biological profile similar to that of 2: a noncompetitive antagonism at nicotinic receptors in the 7-25 mu M range while not showing any antagonism for muscarinic receptors up to 10 mu M. increasing the number of methylenes separating these nitrogen atoms in methoctramine related tetraamines resulted in a significant improvement; in potency at nicotinic receptors. The most potent tetraamine was 19, bearing a 12 methylene spacer between the nitrogen atoms, which was 12-fold and 250-fold more potent than prototypes 1 and 2, respectively. Tetraamines 9-11, bearing a rather rigid spacer between the nitrogen atoms instead of the very flexible polymethylene chain, displayed a profile similar to that of 1 at nicotinic receptors, whereas a significant decrease in potency was observed at muscarinic M-2 receptors. This finding may have relevance in understanding the mode of interaction with these receptors. Similarly, the constrained analogue 12 of methoctramine showed a decrease in potency at nicotinic and muscarinic M-2 receptors, revealing that the tricyclic system, which incorporates the 2-methoxybenzylamine moiety of 1, does not represent a good pharmacophore for activity at these sites. A most intriguing finding was the observation that the photolabile tetraamine 22 was more potent than methoctramine at nicotinic receptors and, what is more important, it inhibited a closed stale of the receptor.

  DOI：

  10.1021/jm991110n
• 作为产物：
  描述：

  6-氨基己酸 在 sodium hydroxide 、 magnesium oxide 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 18.5h， 生成 6-((tert-butoxycarbonyl)amino)hexanoic (ethyl carbonic) anhydride
  参考文献：
  名称：

  Synthesis of Two Acridine Conjugates of the Bis(phenanthroline) Ligand “Clip-Phen” and Evaluation of the Nuclease Activity of the Corresponding Copper Complexes

  摘要：

  DOI：

  10.1002/(sici)1099-0682(199903)1999:3<557::aid-ejic557>3.0.co;2-y

文献信息

• Synthesis and transdermal permeation-enhancing activity of ketone, amide, and alkane analogs of Transkarbam 12
  作者：Tomáš Holas、Kateřina Vávrová、Jana Klimentová、Alexandr Hrabálek

  DOI：10.1016/j.bmc.2005.12.006

  日期：2006.5

  transdermal permeation enhancer. In this study, ketone, amide, and alkane analogs of T12 have been synthesized and evaluated for their permeation-enhancing activity using porcine skin and theophylline as a model drug. Replacement of ester by methylene and ketone, respectively, led to a significant decrease of activity. Amide analogs displayed lower activity in 60% propylene glycol and were comparable to

  Transkarbam 12（5-（十二烷基氧羰基）戊基铵-5-（十二烷基氧羰基）戊基氨基甲酸酯，T12）是一种高活性的透皮渗透促进剂。在这项研究中，已经合成了T12的酮，酰胺和烷烃类似物，并以猪皮肤和茶碱为模型药物评估了它们的渗透增强活性。分别用亚甲基和酮代替酯导致活性显着降低。酰胺类似物在60％丙二醇中的活性较低，与肉豆蔻酸异丙酯中的T12相当。认为酯和氨基甲酸铵基团之间的分子内氢键对于T12的渗透增强活性很重要。
• Structure−Activity Relationships of Methoctramine-Related Polyamines as Muscular Nicotinic Receptor Noncompetitive Antagonists. 3. Effect of Inserting the Tetraamine Backbone into a Macrocyclic Structure
  作者：Maria L. Bolognesi、M. Gabriele Bixel、Gabriella Marucci、Manuela Bartolini、Michael Krauss、Piero Angeli、Alessandra Antonello、Michela Rosini、Vincenzo Tumiatti、Ferdinand Hucho、Carlo Melchiorre

  DOI：10.1021/jm020835f

  日期：2002.7.1

  prototypes, were potent noncompetitive antagonists at both frog and Torpedo nAChRs, suggesting that polyamines do not need to be linear or in extended conformation to optimally interact with the nicotinic channel; rather, they may bind in a U-shaped conformation. Relative to muscarinic activity, macrocyclic compounds 10, 13, 14, and 20, in contrast with the profile displayed by 2, were almost devoid of

  本文扩展了对聚亚甲基四胺结构-活性关系的另一个方面的研究，即，将四胺主链插入大环结构的作用。为此，通过将原型甲基辛特拉明2的两个末端氮原子连接至芳基部分来设计化合物8-12。或者，首先将2修饰以获得化合物6和7，然后通过将两个末端伯胺官能团连接到聚苯基间隔基上将其环化，得到13-20。所有化合物均在肌肉型nAChRs上进行了测试，并且大多数化合物也在AChE上测试。此外，所选的化合物也在外围M（2）和M（3）mAChRs上进行了测试。所有这些环状衍生物都像原型一样，在青蛙和鱼雷nAChRs上都是有效的非竞争性拮抗剂，提示多胺不需要为线性或延伸构象即可与烟碱通道最佳相互作用；相反，它们可能以U形构象结合。相对于毒蕈碱活性，大环化合物10、13、14和20与2显示的特征相反，几乎没有亲和力。推导出芳基间隔基不利于多胺与mAChR的相互作用。最后，在这项研究中研究的所有二胺二酰胺在抑制AChE活
• New nido-carborane-containing conjugates of purine: synthesis and antiviral activity
  作者：D. A. Gruzdev、A. A. Telegina、V. A. Ol’shevskaya、V. L. Andronova、G. A. Galegov、V. V. Zarubaev、G. L. Levit、V. P. Krasnov

  DOI：10.1007/s11172-022-3665-1

  日期：2022.11

  New purine derivatives containing a nido-carborane fragment were synthesized by nucleophilic substitution of chlorine atom in 6-chloropurine and 2-amino-6-chloropurine under the action of nido-carborane-containing amines. Compounds with significant activity against the acyclovir-resistant strain of herpes simplex virus type 1, as well as with moderate activity against influenza viruses A and B, were discovered for the first time among the synthesized nido-carboranyl derivatives of purine.

  在含有尼多硼烷的胺的作用下，通过亲核取代 6-氯嘌呤和 2-氨基-6-氯嘌呤中的氯原子，合成了含有尼多硼烷片段的新嘌呤衍生物。在合成的嘌呤类似硼烷衍生物中，首次发现了对阿昔洛韦抗性 1 型单纯疱疹病毒株有显著活性以及对甲型和乙型流感病毒有中等活性的化合物。
• Design and Synthesis of Simplified Largazole Analogues as Isoform-Selective Human Lysine Deacetylase Inhibitors
  作者：Damodara N. Reddy、Flavio Ballante、Timothy Chuang、Adele Pirolli、Biagina Marrocco、Garland R. Marshall

  DOI：10.1021/acs.jmedchem.5b01632

  日期：2016.2.25

  Selective inhibition of KDAC isoforms while maintaining potency remains a challenge. Using the largazole macrocyclic depsipeptide structure as a starting point for developing new KDACIs with increased selectivity, a combination of four different simplified largazole analogue (SLA) scaffolds with diverse zinc-binding groups (for a total of 60 compounds) were designed, synthesized, and evaluated against class I KDACs 1, 3, and 8, and class II KDAC6. Experimental evidence as well as molecular docking poses converged to establish the cyclic tetrapeptides (CTPs) as the primary determinant of both potency and selectivity by influencing the correct alignment of the zinc-binding group in the KDAC active site, providing a further basis for developing new KDACIs of higher isoform selectivity and potency.