(S,E)-4-[3-(3,5-di-tert-butylphenyl)-3-oxoprop-1-enyl]-2-(3-{2-[2-(2-{2-[4-methyl-2-(4-phenylbutanamido)pentanamido]ethoxy}ethoxy)ethoxy]acetamido}propoxy)benzoic acid | 1351169-28-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (S,E)-4-[3-(3,5-di-tert-butylphenyl)-3-oxoprop-1-enyl]-2-(3-{2-[2-(2-{2-[4-methyl-2-(4-phenylbutanamido)pentanamido]ethoxy}ethoxy)ethoxy]acetamido}propoxy)benzoic acid
• 英文别名: 4-[(E)-3-(3,5-ditert-butylphenyl)-3-oxoprop-1-enyl]-2-[3-[[2-[2-[2-[2-[[(2S)-4-methyl-2-(4-phenylbutanoylamino)pentanoyl]amino]ethoxy]ethoxy]ethoxy]acetyl]amino]propoxy]benzoic acid
• CAS: 1351169-28-2
• 化学式: C₅₁H₇₁N₃O₁₀
• 分子量: 886.139
• InChiKey: LACYKMLIWCKKNS-YIVVRCKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.4
• 重原子数：
  64
• 可旋转键数：
  30
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  179
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-甲基水杨酸甲酯 在 盐酸 、 manganese(IV) oxide 、 N-溴代丁二酰亚胺(NBS) 、 lithium hydroxide monohydrate 、 偶氮二异丁腈 、 sodium methylate 、 三溴化硼 、 sodium hydride 、 potassium carbonate 、 1-羟基苯并三唑 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium iodide 作用下， 以 1,4-二氧六环 、 甲醇 、 四氯化碳 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 112.5h， 生成 (S,E)-4-[3-(3,5-di-tert-butylphenyl)-3-oxoprop-1-enyl]-2-(3-{2-[2-(2-{2-[4-methyl-2-(4-phenylbutanamido)pentanamido]ethoxy}ethoxy)ethoxy]acetamido}propoxy)benzoic acid
  参考文献：
  名称：

  Design, synthesis and biological evaluation of nuclear receptor-degradation inducers

  摘要：

  Compounds that regulate the function(s) of nuclear receptors (NRs) are useful for biological studies and as candidate therapeutic agents. Most such compounds are agonists or antagonists. On the other hand, we have developed specific protein degradation inducers, which we designated as SNIPERs (Specific and Nongenetic IAPs-dependent Protein ERasers), for selective degradation of target proteins. SNIPERs are hybrid molecules consisting of an appropriate ligand for the protein of interest, coupled to a ligand for inhibitor of apoptosis proteins (IAPs), which target the bound protein for polyubiquitination and proteasomal degradation. We considered that protein knockdown with SNIPERs would be a promising alternative approach for modulating NR function. In this study, we designed and synthesized degradation inducers targeting retinoic acid receptor (RAR), estrogen receptor (ER), and androgen receptor (AR). These newly synthesized RAR, ER, and AR SNIPERs, 9, 11, and 13, respectively, were confirmed to significantly reduce the levels of the corresponding NRs in live cells. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.09.041

文献信息

• Design, synthesis and biological evaluation of nuclear receptor-degradation inducers
  作者：Yukihiro Itoh、Risa Kitaguchi、Minoru Ishikawa、Mikihiko Naito、Yuichi Hashimoto

  DOI：10.1016/j.bmc.2011.09.041

  日期：2011.11

  Compounds that regulate the function(s) of nuclear receptors (NRs) are useful for biological studies and as candidate therapeutic agents. Most such compounds are agonists or antagonists. On the other hand, we have developed specific protein degradation inducers, which we designated as SNIPERs (Specific and Nongenetic IAPs-dependent Protein ERasers), for selective degradation of target proteins. SNIPERs are hybrid molecules consisting of an appropriate ligand for the protein of interest, coupled to a ligand for inhibitor of apoptosis proteins (IAPs), which target the bound protein for polyubiquitination and proteasomal degradation. We considered that protein knockdown with SNIPERs would be a promising alternative approach for modulating NR function. In this study, we designed and synthesized degradation inducers targeting retinoic acid receptor (RAR), estrogen receptor (ER), and androgen receptor (AR). These newly synthesized RAR, ER, and AR SNIPERs, 9, 11, and 13, respectively, were confirmed to significantly reduce the levels of the corresponding NRs in live cells. (C) 2011 Elsevier Ltd. All rights reserved.