N-(7-methylpyridino[3,2-e]pyridin-2-yl)-3-((2-(N-(7-methylpyridino[3,2-e]pyridin-2-yl)carbamoyl)ethyl)amino)propanoate | 329325-86-2

• 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: N-(7-methylpyridino[3,2-e]pyridin-2-yl)-3-((2-(N-(7-methylpyridino[3,2-e]pyridin-2-yl)carbamoyl)ethyl)amino)propanoate
• 英文别名: Propanamide, 3,3'-iminobis[N-(7-methyl-1,8-naphthyridin-2-yl)-；N-(7-methyl-1,8-naphthyridin-2-yl)-3-[[3-[(7-methyl-1,8-naphthyridin-2-yl)amino]-3-oxopropyl]amino]propanamide
• CAS: 329325-86-2
• 化学式: C₂₄H₂₅N₇O₂
• 分子量: 443.508
• InChiKey: QZBZQIYEBGGLJT-UHFFFAOYSA-N

物化性质

• 沸点：
  793.8±60.0 °C(Predicted)
• 密度：
  1.335±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(7-methylpyridino[3,2-e]pyridin-2-yl)-3-((2-(N-(7-methylpyridino[3,2-e]pyridin-2-yl)carbamoyl)ethyl)amino)propanoate 在 盐酸 、 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 0.5h， 生成 4-amino-N,N-bis(2-(N-(7-methylpyridino[3,2-e]pyridin-2-yl)carbamoyl)ethyl)butanamide
  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 盐酸 、 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 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 129.0h， 生成 N-(7-methylpyridino[3,2-e]pyridin-2-yl)-3-((2-(N-(7-methylpyridino[3,2-e]pyridin-2-yl)carbamoyl)ethyl)amino)propanoate
  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

• Inhibitors
  申请人：Nakatani Kazuhiko

  公开号：US20070037841A1

  公开（公告）日：2007-02-15

  An inhibitor contains naphthyridine dimer, a naphthyridine-azaquinolone hybrid, a trinaphthyridine-azaquinolone hybrid, or a trinaphthyridine-azaquinolone hybrid derivative. In order to inhibit binding of 100 nM of RRE to 100 nM of Rev protein, for example, an inhibitor containing naphthyridine dimer is used at a molarity of 1.2 μM to 12 μM, an inhibitor containing the naphthyridine-azaquinolone hybrid is used at a molarity of 2 μM to 20 μM, or an inhibitor containing the trinaphthyridine-azaquinolone hybrid derivative is used at a molarity of 200 nM to 2 μM. This makes it possible to effectively inhibit binding of RRE to Rev protein.

  一种抑制剂包含萘啶二聚体、萘啶-氮杂喹啉杂交物、三萘啶-氮杂喹啉杂交物或三萘啶-氮杂喹啉杂交物衍生物。例如，为了抑制100 nM的RRE与100 nM的Rev蛋白质的结合，使用含有萘啶二聚体的抑制剂浓度为1.2 μM至12 μM，使用含有萘啶-氮杂喹啉杂交物的抑制剂浓度为2 μM至20 μM，或使用含有三萘啶-氮杂喹啉杂交物衍生物的抑制剂浓度为200 nM至2 μM。这使得有效地抑制RRE与Rev蛋白质的结合成为可能。
• A new ligand binding to G–G mismatch having improved thermal and alkaline stability
  作者：Tao Peng、Takashi Murase、Yuki Goto、Akio Kobori、Kazuhiko Nakatani

  DOI：10.1016/j.bmcl.2004.11.003

  日期：2005.1

  Naphthyridine dimer (ND) specially binds to guanine-guanine (G-G) mismatch in duplex DNA. In order to improve the thermal and alkaline stability and binding ability of the ligand, we have examined structural modification of the linker. A new ligand (NNC) possessing 2-amino-1,8-naphthyridines and a carbamate linker is much more thermally stable than ND. The half-life of NNC is 2.5 times longer than that of ND at 80degreesC. NNC is also much more stable than ND under alkaline conditions. In addition, NNC binds to G-G mismatch more strongly than ND. The improved stability and the binding of NNC to the G-G mismatch would be suitable for the practical use of NNC-immobilized sensor. (C) 2004 Elsevier Ltd. All rights reserved.
• US7351531B2
  申请人：——

  公开号：US7351531B2

  公开（公告）日：2008-04-01