4-((tert-butoxy)carbonylamino)-N,N-bis(2-(N-(7-methylpyridino[3,2-e]pyridin-2-yl)carbamoyl)ethyl)butanamide | 391247-72-6

• 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: 4-((tert-butoxy)carbonylamino)-N,N-bis(2-(N-(7-methylpyridino[3,2-e]pyridin-2-yl)carbamoyl)ethyl)butanamide
• CAS: 391247-72-6
• 化学式: C₃₃H₄₀N₈O₅
• 分子量: 628.731
• InChiKey: LVRIPZWTXSQPGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.68
• 重原子数：
  46.0
• 可旋转键数：
  12.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  168.4
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  4-((tert-butoxy)carbonylamino)-N,N-bis(2-(N-(7-methylpyridino[3,2-e]pyridin-2-yl)carbamoyl)ethyl)butanamide 在 盐酸 作用下， 以 氯仿 、 乙酸乙酯 为溶剂， 反应 0.5h， 以90%的产率得到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 、 N,N-二异丙基乙胺 、 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 4-((tert-butoxy)carbonylamino)-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