2,5-dioxopyrrolidinyl 3-((tert-butoxy)-N-(2-((2,5-dioxopyrrolidinyl)oxycarbonyl)ethyl)carbonylamino)propanoate | 341978-99-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 2,5-dioxopyrrolidinyl 3-((tert-butoxy)-N-(2-((2,5-dioxopyrrolidinyl)oxycarbonyl)ethyl)carbonylamino)propanoate
• 英文别名: (2,5-Dioxopyrrolidin-1-yl) 3-[[3-(2,5-dioxopyrrolidin-1-yl)oxy-3-oxopropyl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoate
• CAS: 341978-99-2
• 化学式: C₁₉H₂₅N₃O₁₀
• 分子量: 455.422
• InChiKey: WWJASFGKUDZFRC-UHFFFAOYSA-N

物化性质

• 沸点：
  581.0±60.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.22
• 重原子数：
  32.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  156.9
• 氢给体数：
  0.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  2,5-dioxopyrrolidinyl 3-((tert-butoxy)-N-(2-((2,5-dioxopyrrolidinyl)oxycarbonyl)ethyl)carbonylamino)propanoate 在 盐酸 作用下， 以 氯仿 、 乙酸乙酯 为溶剂， 反应 50.0h， 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
• 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 79.0h， 生成 2,5-dioxopyrrolidinyl 3-((tert-butoxy)-N-(2-((2,5-dioxopyrrolidinyl)oxycarbonyl)ethyl)carbonylamino)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

• CONJUGATION LINKERS, CELL BINDING MOLECULE-DRUG CONJUGATES CONTAINING THE LINKERS, METHODS OF MAKING AND USES SUCH CONJUGATES WITH THE LINKERS
  申请人：Hangzhou DAC Biotech Co., Ltd.

  公开号：US20210308277A1

  公开（公告）日：2021-10-07

  The present invention relates to linkers having a group of propiolyl, substituted acryl(acryloyl), or disubstituted propanoyl, and using such linkers for the conjugation of compounds, in particular, cytotoxic agents to a cell-binding molecule.