N-[(2S)-1-[(2S)-2-[[(2S)-1-(3-aminopropylamino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopent-4-en-2-yl]-2-ethylquinoline-3-carboxamide | 1100749-10-7

• 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-[(2S)-1-[(2S)-2-[[(2S)-1-(3-aminopropylamino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopent-4-en-2-yl]-2-ethylquinoline-3-carboxamide
• CAS: 1100749-10-7
• 化学式: C₃₄H₄₂N₆O₄
• 分子量: 598.745
• InChiKey: MXCJCNWLESDMER-DTXPUJKBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  44
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  147
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[(2S)-1-[(2S)-2-[[(2S)-1-(3-aminopropylamino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopent-4-en-2-yl]-2-ethylquinoline-3-carboxamide 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 platinum on activated charcoal 、 氢气 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 30.0h， 生成 N-[(2S,7S)-1,8-bis[(2S)-2-[[(2S)-1-(3-aminopropylamino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-7-[(2-ethylquinoline-3-carbonyl)amino]-1,8-dioxooctan-2-yl]-2-ethylquinoline-3-carboxamide
  参考文献：
  名称：

  Nucleic acid binding compounds and methods of use

  摘要：

  本发明涉及由两个单体之间的二硫键、亚砜硫或烯烃键形成的同源和异源二聚体化合物。还公开了一种制备同源或异源二聚体化合物的方法。本发明还涉及能够形成同源或异源二聚体化合物的单体化合物，以及通过连接一个或多个二聚体形成的寡聚物。还公开了一种抑制目标RNA分子活性的方法，特别是那些具有包括茎或茎环形成的次级结构的RNA分子。公开了能够抑制HIV-I RNA移码茎环和(CUG)n扩展重复茎环活性的二聚体化合物，以及治疗与这些目标RNA分子相关疾病的方法。这些二聚体化合物还可以用于选择性地检测样本中目标RNA分子的存在。

  公开号：

  US09212205B2
• 作为产物：
  描述：

  2-ethyl-quinoline-3-carboxylic acid 、 Fmoc-L-脯氨酸 、 Fmoc-L-苯丙氨酸 、 Fmoc-L-烯丙基甘氨酸 、 1,3-丙二胺 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 、 二氯甲烷 为溶剂， 反应 1.5h， 以0.23 g的产率得到N-[(2S)-1-[(2S)-2-[[(2S)-1-(3-aminopropylamino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopent-4-en-2-yl]-2-ethylquinoline-3-carboxamide
  参考文献：
  名称：

  Strategies for Recognition of Stem−Loop RNA Structures by Synthetic Ligands: Application to the HIV-1 Frameshift Stimulatory Sequence

  摘要：

  Production of the Gag-Pol polyprotein in human immunodeficiency virus (HIV) requires a -1 ribosomal frameshift, which is directed by a highly conserved RNA stern-loop. Building on our discovery of a set of disulfide-containing peptides that bind this RNA, we describe medicinal chemistry efforts designed to begin to understand the structure-activity relationships and RNA sequence-selectivity relationships associated with these compounds. Additionally, we have prepared analogues incorporating an olefin or saturated hydrocarbon bioisostere of the disulfide moiety, as a first step toward enhancing biostability. The olefin-containing compounds exhibit affinity comparable to the lead disulfide and, importantly, have no discernible toxicity when incubated with human fibroblasts at concentrations up to 1 mM.

  DOI：

  10.1021/jm100231t

文献信息

• Nucleic acid binding compounds and methods of use
  申请人：Miller Benjamin L.

  公开号：US09212205B2

  公开（公告）日：2015-12-15

  The present invention relates to homo- and hetero-dimer compounds formed by a disulfide, sulfinyl thio, or olefin bond between two monomers. A method of making a homo- or hetero-dimer compound is also disclosed. The present invention also relates to monomer compounds capable of forming homo- or hetero-dimer compounds, as well as oligomers formed via linkage of one or more dimers. Also disclosed are methods of inhibiting the activity of target RNA molecules, particularly those having a secondary structure that include a stem or stem-loop formation. Dimer compounds capable of inhibiting the activity of an HIV-I RNA frameshifting stem-loop and a (CUG)n expanded repeat stem-loop are disclosed, as are methods of treating diseases associated with these target RNA molecules. The dimer compounds can also be used for selectively detecting presence of the target RNA molecule in a sample.

  本发明涉及由两个单体之间的二硫键、亚砜硫或烯烃键形成的同源和异源二聚体化合物。还公开了一种制备同源或异源二聚体化合物的方法。本发明还涉及能够形成同源或异源二聚体化合物的单体化合物，以及通过连接一个或多个二聚体形成的寡聚物。还公开了一种抑制目标RNA分子活性的方法，特别是那些具有包括茎或茎环形成的次级结构的RNA分子。公开了能够抑制HIV-I RNA移码茎环和(CUG)n扩展重复茎环活性的二聚体化合物，以及治疗与这些目标RNA分子相关疾病的方法。这些二聚体化合物还可以用于选择性地检测样本中目标RNA分子的存在。
• Strategies for Recognition of Stem−Loop RNA Structures by Synthetic Ligands: Application to the HIV-1 Frameshift Stimulatory Sequence
  作者：Prakash B. Palde、Leslie O. Ofori、Peter C. Gareiss、Jaclyn Lerea、Benjamin L. Miller

  DOI：10.1021/jm100231t

  日期：2010.8.26

  Production of the Gag-Pol polyprotein in human immunodeficiency virus (HIV) requires a -1 ribosomal frameshift, which is directed by a highly conserved RNA stern-loop. Building on our discovery of a set of disulfide-containing peptides that bind this RNA, we describe medicinal chemistry efforts designed to begin to understand the structure-activity relationships and RNA sequence-selectivity relationships associated with these compounds. Additionally, we have prepared analogues incorporating an olefin or saturated hydrocarbon bioisostere of the disulfide moiety, as a first step toward enhancing biostability. The olefin-containing compounds exhibit affinity comparable to the lead disulfide and, importantly, have no discernible toxicity when incubated with human fibroblasts at concentrations up to 1 mM.