2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-phenylpropanoic acid | 678992-21-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-phenylpropanoic acid
• 英文别名: 2-(((9H-Fluoren-9-YL)methoxy)carbonylamino)-2-phenylpropanoic acid；2-(9H-fluoren-9-ylmethoxycarbonylamino)-2-phenylpropanoic acid
• CAS: 678992-21-7
• 化学式: C₂₄H₂₁NO₄
• 分子量: 387.435
• InChiKey: BGAVVPDORCZLJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  DL-2-氨基-2-苯基丙酸 、 9-芴甲基-N-琥珀酰亚胺基碳酸酯 在 phosphate buffer 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-phenylpropanoic acid
  参考文献：
  名称：

  Novel Selective Inhibitors of the Interaction of Individual Nuclear Hormone Receptors with a Mutually Shared Steroid Receptor Coactivator 2

  摘要：

  Nuclear hormone receptor (NR) signaling, currently a therapeutic target in multiple diseases, involves an ordered series of protein interactions to regulate transcription in response to changing hormone levels. Later steps in the process of ligand-dependent signaling are driven by a highly conserved interaction between the NRs and the steroid receptor coactivators (SRCs) that is effected by a conserved interaction motif (L1XXL2L3), known as an NR box. Using computational design and combinatorial chemistry, we have produced novel alpha-helical proteomimetics of the second NR box of SRC2 that exploit structural differences between human estrogen receptor alpha (hERalpha), human estrogen receptor beta (hERbeta), and human thyroid hormone receptor beta (hTRbeta). The resulting library sequentially replaced each leucine with non-natural side chains. Screening this library using a quantitative competition assay revealed compounds that selectively inhibit the interaction of SRC2-2 with each individual NR in preference to its interaction with the other NR. This approach generated highly selective compounds from one that had no specificity for a particular family member. These compounds represent the first family-member-selective competitive inhibitors of the protein interactions of transcription factors.

  DOI：

  10.1021/ja0348391

文献信息

• Backbone modifications in peptidic inhibitors of flaviviral proteases
  作者：Alexander K.M.H. Jakob、Tom R. Sundermann、Christian D. Klein

  DOI：10.1016/j.bmcl.2019.05.054

  日期：2019.8

  The NS2B-NS3 protease is a promising target for the development of drugs against dengue virus (DENV), West Nile virus (WNV) and related flaviviruses. We report the systematic variation of the peptide backbone of the two lead compounds Bz-Arg-Lys-D-Phg-NH2 and Bz-Arg-Lys-D-Phg(OBn)-NH2. While inhibitory activity against WNV protease was generally decreased, the inhibitory potency against DENV protease could be conserved and increased in several peptidomimetics, particularly in those containing a (NMe)arginine fragment or an N-terminal alpha-keto amide. Methylation at the alpha-position of the C-terminal phenylglycine led to a 6-fold higher potency against DENV protease. Peptidomimetics with modified backbone showed increased resistance against hydrolytic attack by trypsin and alpha-chymotrypsin.
• Novel Selective Inhibitors of the Interaction of Individual Nuclear Hormone Receptors with a Mutually Shared Steroid Receptor Coactivator 2
  作者：Timothy R. Geistlinger、R. Kiplin Guy

  DOI：10.1021/ja0348391

  日期：2003.6.1

  Nuclear hormone receptor (NR) signaling, currently a therapeutic target in multiple diseases, involves an ordered series of protein interactions to regulate transcription in response to changing hormone levels. Later steps in the process of ligand-dependent signaling are driven by a highly conserved interaction between the NRs and the steroid receptor coactivators (SRCs) that is effected by a conserved interaction motif (L1XXL2L3), known as an NR box. Using computational design and combinatorial chemistry, we have produced novel alpha-helical proteomimetics of the second NR box of SRC2 that exploit structural differences between human estrogen receptor alpha (hERalpha), human estrogen receptor beta (hERbeta), and human thyroid hormone receptor beta (hTRbeta). The resulting library sequentially replaced each leucine with non-natural side chains. Screening this library using a quantitative competition assay revealed compounds that selectively inhibit the interaction of SRC2-2 with each individual NR in preference to its interaction with the other NR. This approach generated highly selective compounds from one that had no specificity for a particular family member. These compounds represent the first family-member-selective competitive inhibitors of the protein interactions of transcription factors.