(2S)-2-[(3S)-3-benzyl-4-[(2S)-2-[(3S)-3-[(4-chlorophenyl)methyl]-2-oxopiperazin-1-yl]-3-(1H-indol-3-yl)propanoyl]-2-oxopiperazin-1-yl]-4-methylpentanamide | 1610618-53-5

• 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: (2S)-2-[(3S)-3-benzyl-4-[(2S)-2-[(3S)-3-[(4-chlorophenyl)methyl]-2-oxopiperazin-1-yl]-3-(1H-indol-3-yl)propanoyl]-2-oxopiperazin-1-yl]-4-methylpentanamide
• CAS: 1610618-53-5
• 化学式: C₃₉H₄₅ClN₆O₄
• 分子量: 697.277
• InChiKey: YDTPUSGASWQHEB-BBACVFHCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  50
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  132
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  tert-butyl N-[[1-[3-(4-chlorophenyl)propanoyl]piperidin-3-yl]methyl]carbamate 、 Fmoc-L-苯丙氨酸 、 Fmoc-L-色氨酸 、 2-溴乙醇 、 N-芴甲氧羰基-L-4-氯苯丙氨酸 在 哌啶 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (2S)-2-[(3S)-3-benzyl-4-[(2S)-2-[(3S)-3-[(4-chlorophenyl)methyl]-2-oxopiperazin-1-yl]-3-(1H-indol-3-yl)propanoyl]-2-oxopiperazin-1-yl]-4-methylpentanamide
  参考文献：
  名称：

  Rational Design of Topographical Helix Mimics as Potent Inhibitors of Protein–Protein Interactions

  摘要：

  Protein-protein interactions encompass large surface areas, but often a handful of key residues dominate the binding energy landscape. Rationally designed small molecule scaffolds that reproduce the relative positioning and disposition of important binding residues, termed "hotspot residues", have been shown to successfully inhibit specific protein complexes. Although this strategy has led to development of novel synthetic inhibitors of protein complexes, often direct mimicry of natural amino acid residues does not lead to potent inhibitors. Experimental screening of focused compound libraries is used to further optimize inhibitors but the number of possible designs that can be efficiently synthesized and experimentally tested in academic settings is limited. We have applied the principles of computational protein design to optimization of nonpeptidic helix mimics as ligands for protein complexes. We describe the development of computational tools to design helix mimetics from canonical and noncanonical residue libraries and their application to two therapeutically important protein-protein interactions: p53-MDM2 and p300-HIF1 alpha. The overall study provides a streamlined approach for discovering potent peptidomimetic inhibitors of protein-protein interactions.

  DOI：

  10.1021/ja502310r

文献信息

• Oxopiperazine helix mimetics as inhibitors of the p53-MDM2 interaction
  申请人：NEW YORK UNIVERSITY

  公开号：US11180481B2

  公开（公告）日：2021-11-23

  The present invention relates to oligooxopiperazines for modulating the p53-Mdm2 interaction. Exemplary oligooxopiperazines include those of Formula IA, Formula IB, and Formula IC below (wherein the various substituents are as defined herein). Methods of using the oligooxopiperazines are also disclosed.

  本发明涉及用于调节 p53-Mdm2 相互作用的寡氧哌嗪。示例性的低聚氧哌嗪包括下式 IA、式 IB 和式 IC 的低聚氧哌嗪（其中各种取代基如本文所定义）。还公开了使用这些寡氧哌嗪的方法。
• OXOPIPERAZINE HELIX MIMETICS AS INHIBITORS OF THE p53-MDM2 INTERACTION
  申请人：ARORA Paramjit S.

  公开号：US20170037033A1

  公开（公告）日：2017-02-09

  The present invention relates to oligooxopiperzines for modulating the p53-Mdm2 interaction. Methods of using the oligooxopiperazines are also disclosed.
• Rational Design of Topographical Helix Mimics as Potent Inhibitors of Protein–Protein Interactions
  作者：Brooke Bullock Lao、Kevin Drew、Danielle A. Guarracino、Thomas F. Brewer、Daniel W. Heindel、Richard Bonneau、Paramjit S. Arora

  DOI：10.1021/ja502310r

  日期：2014.6.4

  Protein-protein interactions encompass large surface areas, but often a handful of key residues dominate the binding energy landscape. Rationally designed small molecule scaffolds that reproduce the relative positioning and disposition of important binding residues, termed "hotspot residues", have been shown to successfully inhibit specific protein complexes. Although this strategy has led to development of novel synthetic inhibitors of protein complexes, often direct mimicry of natural amino acid residues does not lead to potent inhibitors. Experimental screening of focused compound libraries is used to further optimize inhibitors but the number of possible designs that can be efficiently synthesized and experimentally tested in academic settings is limited. We have applied the principles of computational protein design to optimization of nonpeptidic helix mimics as ligands for protein complexes. We describe the development of computational tools to design helix mimetics from canonical and noncanonical residue libraries and their application to two therapeutically important protein-protein interactions: p53-MDM2 and p300-HIF1 alpha. The overall study provides a streamlined approach for discovering potent peptidomimetic inhibitors of protein-protein interactions.