N-(tert-butoxycarbonyl)imino-3,3'-bis(pentafluorophenyl) propionate | 391247-73-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: N-(tert-butoxycarbonyl)imino-3,3'-bis(pentafluorophenyl) propionate
• 英文别名: bis(perfluorophenyl) 3,3'-((tertbutoxycarbonyl)azanediyl) dipropionate；(2,3,4,5,6-Pentafluorophenyl) 3-[tert-butoxycarbonyl-[3-oxo-3-(2,3,4,5,6-pentafluorophenoxy)propyl]amino]propanoate；(2,3,4,5,6-pentafluorophenyl) 3-[(2-methylpropan-2-yl)oxycarbonyl-[3-oxo-3-(2,3,4,5,6-pentafluorophenoxy)propyl]amino]propanoate
• CAS: 391247-73-7
• 化学式: C₂₃H₁₇F₁₀NO₆
• 分子量: 593.375
• InChiKey: BWBPJDJYOWZGGZ-UHFFFAOYSA-N

物化性质

• 沸点：
  535.7±50.0 °C(Predicted)
• 密度：
  1.505±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.61
• 重原子数：
  40.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  82.14
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-(tert-butoxycarbonyl)imino-3,3'-bis(pentafluorophenyl) propionate 在 N,N-二异丙基乙胺 作用下， 以 氯仿 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 63.5h， 生成 N-(7-methylpyridino[3,2-e]pyridin-2-yl)-3-((2-(N-(2-quinolyl)carbamoyl)ethyl)amino)propanamide hydrochloride
  参考文献：
  名称：

  Recognition of Guanine−Guanine Mismatches by the Dimeric Form of 2-Amino-1,8-naphthyridine

  摘要：

  Dimeric 2-amino-1,8-naphthyridine selectively binds to a G-G mismatch with hi-h affinity (K-d = 53 nM). We have investigated a binding mechanism of naphthyridine dimer 2 to a G-G mismatch by spectroscopic studies, thermodynamic analysis, and structure-activity studies for the thermal stabilization of the mismatch. H-1 NMR spectra of a complex of 2 with 9-mer duplex d(CATCGGATG)(2) containing a G-G mismatch showed that all hydrogens in two naphthyridine rings of 2 were observed upfield compared to those C of 2 in a free state. The 2D-NOESY experiments showed that each naphthyridine of 2 binds to a guanine in the, G-G mismatch within the pi -stack. In CD spectra, a large conformational change of the G-G mismatch-containing duplex was observed upon complex formation with 2. Isothermal calorimetry titration of 2 binding to the G-G mismatch showed that the stoichiometry for the binding is about 1:1 and that the binding is enthalpy-controlled. It is clarified by structure-activity studies that show (i) the linker connecting two naphthyridine rings was essential for the stabilization of the G-G mismatch, (ii) the binding efficiency was very sensitive to the linker structure, and (iii) the binding of two naphthyridines to each one of two Gs in the G-G pi -dsmatch is essential for a strong stabilization. These results strongly supported the intercalation of both naphthyridine rings of 2 into DNA base pairs and the formation of a hydrogen bonded complex with the G-G mismatch.

  DOI：

  10.1021/ja0109186
• 作为产物：
  描述：

  双(2-氰基乙基)胺 在 sodium hydroxide 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 乙酰氯 作用下， 以 四氢呋喃 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 55.0h， 生成 N-(tert-butoxycarbonyl)imino-3,3'-bis(pentafluorophenyl) propionate
  参考文献：
  名称：

  Recognition of Guanine−Guanine Mismatches by the Dimeric Form of 2-Amino-1,8-naphthyridine

  摘要：

  Dimeric 2-amino-1,8-naphthyridine selectively binds to a G-G mismatch with hi-h affinity (K-d = 53 nM). We have investigated a binding mechanism of naphthyridine dimer 2 to a G-G mismatch by spectroscopic studies, thermodynamic analysis, and structure-activity studies for the thermal stabilization of the mismatch. H-1 NMR spectra of a complex of 2 with 9-mer duplex d(CATCGGATG)(2) containing a G-G mismatch showed that all hydrogens in two naphthyridine rings of 2 were observed upfield compared to those C of 2 in a free state. The 2D-NOESY experiments showed that each naphthyridine of 2 binds to a guanine in the, G-G mismatch within the pi -stack. In CD spectra, a large conformational change of the G-G mismatch-containing duplex was observed upon complex formation with 2. Isothermal calorimetry titration of 2 binding to the G-G mismatch showed that the stoichiometry for the binding is about 1:1 and that the binding is enthalpy-controlled. It is clarified by structure-activity studies that show (i) the linker connecting two naphthyridine rings was essential for the stabilization of the G-G mismatch, (ii) the binding efficiency was very sensitive to the linker structure, and (iii) the binding of two naphthyridines to each one of two Gs in the G-G pi -dsmatch is essential for a strong stabilization. These results strongly supported the intercalation of both naphthyridine rings of 2 into DNA base pairs and the formation of a hydrogen bonded complex with the G-G mismatch.

  DOI：

  10.1021/ja0109186

文献信息

• The Dimeric Form of 1,3‐Diaminoisoquinoline Derivative Rescued the Mis‐splicing of <i>Atp2a1</i> and <i>Clcn1</i> Genes in Myotonic Dystrophy Type 1 Mouse Model
  作者：Jun Matsumoto、Masayuki Nakamori、Tatsumasa Okamoto、Asako Murata、Chikara Dohno、Kazuhiko Nakatani

  DOI：10.1002/chem.202001572

  日期：2020.11.11

  CUG repeat RNA in the dystrophia myotonia protein kinase (DMPK) gene causes myotonic dystrophy type 1 (DM1) and sequesters RNA processing proteins, such as the splicing factor muscleblind‐like 1 protein (MBNL1). Sequestration of splicing factors results in the mis‐splicing of some pre‐mRNAs. Small molecules that rescue the mis‐splicing in the DM1 cells have drawn attention as potential drugs to treat

  肌营养不良性肌强直蛋白激酶（DMPK）基因中CUG重复RNA的扩增会导致1型肌强直性营养不良（DM1）并隔离RNA处理蛋白，例如剪接因子Musblindlike 1蛋白（MBNL1）。剪接因子的隔离导致某些pre-mRNA的错误剪接。拯救DM1细胞中错接的小分子作为治疗DM1的潜在药物引起了人们的注意。在本文中，我们报道了一个新分子JM642，该分子由两个1,3-二氨基异喹啉发色团组成，在C5位置具有一个辅助芳香单元。JM642在DM1细胞模型以及Clcn1和Atp2a1中交替显示Ldb3基因的pre-mRNA的剪接模式DM1小鼠模型中的基因。通过表面等离振子共振（SPR）测定法对r（CUG）重复进行体外结合分析以及DM1细胞模型中核糖核酸灶的破坏，表明JM642与体内扩增的r（CUG）重复序列结合，最终挽救了误拼接。
• Naphthyridine-Benzoazaquinolone: Evaluation of a Tricyclic System for the Binding to (CAG)_<i>n</i>Repeat DNA and RNA
  作者：Jinxing Li、Akihiro Sakata、Hanping He、Li-Ping Bai、Asako Murata、Chikara Dohno、Kazuhiko Nakatani

  DOI：10.1002/asia.201600527

  日期：2016.7.5

  CAG repeat DNA and RNA. One derivative, NBzA, modified by incorporating an additional ring to the azaquinolone was found to bind to both d(CAG)9 and r(CAG)9. NBzA binding to d(CAG)9 was similar to NA binding in terms of large changes in the SPR assay and circular dichroism (CD) as well as pairwise binding, as assessed by electron spray ionization time‐of‐flight (ESI‐TOF) mass spectrometry. For the binding

  CAG重复序列在人类基因组中的扩增会导致神经系统疾病亨廷顿氏病。我们报道过，小分子萘啶-氮杂喹啉酮NA早先与CAG重复DNA的发夹结构中的CAG / CAG基序结合。为了研究和改善NA与CAG重复序列DNA和RNA的结合，我们进行了NA与CAG重复序列的系统结构结合研究。在我们合成的五种新的NA衍生物中，表面等离子体共振（SPR）分析表明，从NA中的酰胺键修饰为氨基甲酸酯键的所有衍生物均无法与CAG重复DNA和RNA结合。一种衍生物，NBzA被发现通过结合一个额外的环到azaquinolone进行了修饰的，与d（CAG）9和r（CAG）9都结合。NBzA与d（CAG）9的结合在SPR分析和圆二色性（CD）以及成对结合方面发生了巨大变化，与NA结合相似，通过电子喷雾电离飞行时间（ESI-TOF）进行评估质谱。对于与r（CAG）9的结合，NA和NBzA在ESI-TOF MS中均显示出逐步结合，
• A Dimeric 2,9‐Diamino‐1,10‐phenanthroline Derivative Improves Alternative Splicing in Myotonic Dystrophy Type 1 Cell and Mouse Models
  作者：Jinxing Li、Masayuki Nakamori、Jun Matsumoto、Asako Murata、Chikara Dohno、Agnieszka Kiliszek、Katarzyna Taylor、Krzysztof Sobczak、Kazuhiko Nakatani

  DOI：10.1002/chem.201804368

  日期：2018.12.5

  the cause of the neurological disorder myotonic dystrophy type 1 (DM1). The pathological features of DM1 include the formation of ribonuclear foci containing expanded r(CUG) repeats, which sequester the MBNL1 protein and lead to the misregulation of alternative pre‐mRNA splicing. Small molecules that bind to the r(CUG) repeats and improve alternative splicing have therapeutic potential in the treatment

  扩大的r（CUG）重复是神经系统疾病1型强直性营养不良（DM1）的原因。DM1的病理学特征包括含有扩展的r（CUG）重复序列的核仁病灶的形成，其螯合了MBNL1蛋白并导致了替代的pre-mRNA剪接的错误调控。结合到r（CUG）重复序列并改善选择性剪接的小分子在DM1的治疗中具有治疗潜力。在此，报道了DDAP的合成（先前报道的CUG结合分子DAP的二聚体形式），其与r（CUG）的结合特性重复以及对错接剪接的影响。表面等离子体共振分析，圆二色性光谱和ESI-TOF质谱结果证实了DDAP的结合至r（CUG）9重复。对DM1细胞模型和DM1小鼠模型的研究表明，DDAP在恢复pre-mRNA剪接缺陷方面部分有效。通过竞争性结合试验对恢复的基础进行了体外研究，结果表明DDAP可能以浓度依赖的方式干扰MBNL1与r（CUG）重复序列的结合。
• A Small Molecule Affecting the Replication of Trinucleotide Repeat d(GAA)<i>n</i>
  作者：Hanping He、Masaki Hagihara、Kazuhiko Nakatani

  DOI：10.1002/chem.200901088

  日期：2009.10.12

  methylcarbamoylnaphthyridine dimer (MCND), was synthesized and characterized. Ligand binding to d(GAA)10 was investigated by UV thermal denaturation, circular dichroism spectroscopy, surface plasmon resonance, and cold‐spray‐ionization time‐of‐flight mass spectrometry. The results indicated that MCND bound to the d(GAA)n repeat to form a stable hairpin structure with a major binding stoichiometry of 3:1. The most

  合成并表征了新设计的配体，甲基氨基甲酰基萘啶二聚体（MCND）。通过紫外热变性，圆二色谱，表面等离子体共振和冷喷雾电离飞行时间质谱研究了配体与d（GAA）10的结合。结果表明，与d（GAA）n结合的MCND重复形成稳定的发夹结构，主要化学计量比为3：1。在AGA / AGA三联体中，最可能的结合位点被鉴定为GG不匹配。聚合酶终止试验表明MCND与d（GAA）n重复序列的结合有效地干扰了带有两个原核Taq的模板前两个GAA位点上引物的延伸 DNA聚合酶和人类DNA聚合酶α。
• The SPR Sensor Detecting Cytosine−Cytosine Mismatches
  作者：Akio Kobori、Souta Horie、Hitoshi Suda、Isao Saito、Kazuhiko Nakatani

  DOI：10.1021/ja037947w

  日期：2004.1.1

  We have synthesized the first surface plasmon resonance (SPIR) sensor that detects cytosine-cytosine (C-C) mismatches in duplex DNA by immobilizing aminonaphthyridine dinner on the gold surface. The ligand consisting of two 2-aminonaphthyridine chromophores and an alkyl linker connecting them strongly stabilized the C-C mismatches regardless of the flanking sequences. The fully matched duplexes were not stabilized at all under the same conditions. The C-T, C-A, and T-T mismatches were also stabilized with a reduced efficiency. SPR analyses of mismatch-containing 27-mer duplexes were performed with the sensor surface on which the aminonaphthyridine dimer was immobilized. The response for the C-C mismatch in 5'-GCC-3/3'-CCG-5' was about 83 times stronger than that obtained for the fully matched duplex. The sensor successfully detects the C-C mismatch at the concentration of 10 nM. SPR responses are proportional to the concentration of the C-C mismatch in a range up to 200 nM. Aminonaphthyridine dinner could bind strongly to the C-C mismatches having 10 possible flanking sequences with association constants in the order of 10(6) M-1. The facile protonation of 2-aminonaphthyridine chromophore at pH 7 producing the hydrogen-bonding surface complementary to that of cytosine was most likely due to the remarkably high selectivity of 1 to the C-C mismatch.