N-2-(3-phenoxyphenyl)acetyl-L-Asn-L-Val-(S)-NHCH(CH₃)Ph

• 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-2-(3-phenoxyphenyl)acetyl-L-Asn-L-Val-(S)-NHCH(CH₃)Ph
• 英文别名: (2S)-N-[(2S)-3-methyl-1-oxo-1-[[(1S)-1-phenylethyl]amino]butan-2-yl]-2-[[2-(3-phenoxyphenyl)acetyl]amino]butanediamide
• 化学式: C₃₁H₃₆N₄O₅
• 分子量: 544.651
• InChiKey: KFSKVYHMCPJMMO-VFXRXZKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  40
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  L-缬氨酸苄酯对甲苯磺酸盐 在 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-2-(3-phenoxyphenyl)acetyl-L-Asn-L-Val-(S)-NHCH(CH₃)Ph
  参考文献：
  名称：

  Discovery of novel non-covalent inhibitors selective to the β5-subunit of the human 20S proteasome

  摘要：

  A series of linear peptides (6a-6o) were designed based on the known non-covalent 20S proteasome inhibitors TMC-95A and compound 5 via a fragment-based approach. These compounds were synthesized and evaluated against the chymotrypsin-like activity of the human 20S proteasome. Three of them (6d, 6e and 6k) were potent inhibitors with IC50 values at the submicromolar level. These three compounds were selective to the beta 5-subunit and showed no obvious inhibition against trypsin-like and caspase-like activities of the human 20S proteasome. Docking study of the most potent compound 6e revealed its key interactions with the beta 5-subunit of the 20S proteasome. These findings have provided a new chemical template for non-covalent proteasome inhibitors, which is ready for further structural optimization to improve both potency and subunit selectivity. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.05.023

文献信息

• Discovery of novel non-covalent inhibitors selective to the β5-subunit of the human 20S proteasome
  作者：Kai Xu、Ke Wang、Ying Yang、Ding-An Yan、Li Huang、Chin-Ho Chen、Zhiyan Xiao

  DOI：10.1016/j.ejmech.2015.05.023

  日期：2015.6

  A series of linear peptides (6a-6o) were designed based on the known non-covalent 20S proteasome inhibitors TMC-95A and compound 5 via a fragment-based approach. These compounds were synthesized and evaluated against the chymotrypsin-like activity of the human 20S proteasome. Three of them (6d, 6e and 6k) were potent inhibitors with IC50 values at the submicromolar level. These three compounds were selective to the beta 5-subunit and showed no obvious inhibition against trypsin-like and caspase-like activities of the human 20S proteasome. Docking study of the most potent compound 6e revealed its key interactions with the beta 5-subunit of the 20S proteasome. These findings have provided a new chemical template for non-covalent proteasome inhibitors, which is ready for further structural optimization to improve both potency and subunit selectivity. (C) 2015 Elsevier Masson SAS. All rights reserved.