3-{tert-Butoxycarbonyl-[2-(7-methyl-[1,8]naphthyridin-2-ylcarbamoyl)-ethyl]-amino}-propionic acid pentafluorophenyl ester | 391247-74-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-{tert-Butoxycarbonyl-[2-(7-methyl-[1,8]naphthyridin-2-ylcarbamoyl)-ethyl]-amino}-propionic acid pentafluorophenyl ester
• CAS: 391247-74-8
• 化学式: C₂₆H₂₅F₅N₄O₅
• 分子量: 568.5
• InChiKey: CYZQROJNPNNRJP-UHFFFAOYSA-N

物化性质

• 沸点：
  676.7±55.0 °C(Predicted)
• 密度：
  1.402±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  40.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  110.72
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  3-{tert-Butoxycarbonyl-[2-(7-methyl-[1,8]naphthyridin-2-ylcarbamoyl)-ethyl]-amino}-propionic acid pentafluorophenyl ester 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 48.5h， 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 、 N,N-二异丙基乙胺 、 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 70.0h， 生成 3-{tert-Butoxycarbonyl-[2-(7-methyl-[1,8]naphthyridin-2-ylcarbamoyl)-ethyl]-amino}-propionic acid pentafluorophenyl ester
  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

• 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，