ethyl 1-methyl-4-(1-methyl-4-(4-dimethylaminobutyryl)amino)pyrrole-2-carboxylate | 300711-22-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: ethyl 1-methyl-4-(1-methyl-4-(4-dimethylaminobutyryl)amino)pyrrole-2-carboxylate
• 英文别名: Ethyl 4-[[4-[4-(dimethylamino)butanoylamino]-1-methylpyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carboxylate
• CAS: 300711-22-2
• 化学式: C₂₀H₂₉N₅O₄
• 分子量: 403.481
• InChiKey: SBYZTUKFJIIOEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  97.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 1-methyl-4-(1-methyl-4-(4-dimethylaminobutyryl)amino)pyrrole-2-carboxylate 在 N-甲基吗啉 、 sodium hydroxide 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 4-(dimethylamino)-N-[5-[[5-[[5-[[5-[[5-[[5-[3-(dimethylamino)propylcarbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]butanimidic acid
  参考文献：
  名称：

  DNA Binding, Solubility, and Partitioning Characteristics of Extended Lexitropsins

  摘要：

  Four new ligands that bind to the minor groove of DNA have been designed, synthesized, and evaluated by DNA footprinting. Two of the ligands are polyamides containing central regions with five or six N-methylpyrrole units, conferring hydrophobicity and good binding affinity but without retaining the correct spacing for hydrogen bonding in the base of the minor groove. The two remaining ligands have central regions which are head-to-head-linked polyamides, in which the linker is designed to improve the phasing of hydrogen bonding of the ligand with the floor of the minor groove. The highest affinity was obtained with the two polypyrroles without headgroup spacers, indicating that H-bond phasing is secondary in determining affinity compared to the major hydrophobic driving force. With a dimethylaminoalkyl group, representing a moiety with modest base strength, at both ends, water solubility is good and pH-partition theory predicts that penetration through lipid membranes will be enhanced, compared to strongly basic amidine analogues of the alkaloid precursors. All four compounds bind to DNA, with strong selectivity for AT sequences but some tolerance of GC base pairs and subtle individual preferences. The data show that very high affinities can be anticipated for future compounds in this series, but drug design must take account of overall physicochemical properties as well as the details of hydrogen bonding between ligands and the floor of the minor groove.

  DOI：

  10.1021/jm990620e
• 作为产物：
  描述：

  1-甲基-4-硝基吡咯-2-羧酸 在 10percent Pd/C 氯化亚砜 、 氢气 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 乙二醇二甲醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 ethyl 1-methyl-4-(1-methyl-4-(4-dimethylaminobutyryl)amino)pyrrole-2-carboxylate
  参考文献：
  名称：

  DNA Binding, Solubility, and Partitioning Characteristics of Extended Lexitropsins

  摘要：

  Four new ligands that bind to the minor groove of DNA have been designed, synthesized, and evaluated by DNA footprinting. Two of the ligands are polyamides containing central regions with five or six N-methylpyrrole units, conferring hydrophobicity and good binding affinity but without retaining the correct spacing for hydrogen bonding in the base of the minor groove. The two remaining ligands have central regions which are head-to-head-linked polyamides, in which the linker is designed to improve the phasing of hydrogen bonding of the ligand with the floor of the minor groove. The highest affinity was obtained with the two polypyrroles without headgroup spacers, indicating that H-bond phasing is secondary in determining affinity compared to the major hydrophobic driving force. With a dimethylaminoalkyl group, representing a moiety with modest base strength, at both ends, water solubility is good and pH-partition theory predicts that penetration through lipid membranes will be enhanced, compared to strongly basic amidine analogues of the alkaloid precursors. All four compounds bind to DNA, with strong selectivity for AT sequences but some tolerance of GC base pairs and subtle individual preferences. The data show that very high affinities can be anticipated for future compounds in this series, but drug design must take account of overall physicochemical properties as well as the details of hydrogen bonding between ligands and the floor of the minor groove.

  DOI：

  10.1021/jm990620e

文献信息

• DNA Binding, Solubility, and Partitioning Characteristics of Extended Lexitropsins
  作者：Robert V. Fishleigh、Keith R. Fox、Abedawn I. Khalaf、Andrew R. Pitt、Martin Scobie、Colin J. Suckling、John Urwin、Roger D. Waigh、Stephen C. Young

  DOI：10.1021/jm990620e

  日期：2000.8.1

  Four new ligands that bind to the minor groove of DNA have been designed, synthesized, and evaluated by DNA footprinting. Two of the ligands are polyamides containing central regions with five or six N-methylpyrrole units, conferring hydrophobicity and good binding affinity but without retaining the correct spacing for hydrogen bonding in the base of the minor groove. The two remaining ligands have central regions which are head-to-head-linked polyamides, in which the linker is designed to improve the phasing of hydrogen bonding of the ligand with the floor of the minor groove. The highest affinity was obtained with the two polypyrroles without headgroup spacers, indicating that H-bond phasing is secondary in determining affinity compared to the major hydrophobic driving force. With a dimethylaminoalkyl group, representing a moiety with modest base strength, at both ends, water solubility is good and pH-partition theory predicts that penetration through lipid membranes will be enhanced, compared to strongly basic amidine analogues of the alkaloid precursors. All four compounds bind to DNA, with strong selectivity for AT sequences but some tolerance of GC base pairs and subtle individual preferences. The data show that very high affinities can be anticipated for future compounds in this series, but drug design must take account of overall physicochemical properties as well as the details of hydrogen bonding between ligands and the floor of the minor groove.