N-{3-{(2S)-1-[(2S)-4-methyl-1-((2R)-2-methyloxiran-2-yl)-1-oxopentan-2-ylamino]-1-oxo-3-phenylpropan-2-ylamino}-3-oxo-1-phenylpropyl}-2-naphthamide | 1609959-76-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: N-{3-{(2S)-1-[(2S)-4-methyl-1-((2R)-2-methyloxiran-2-yl)-1-oxopentan-2-ylamino]-1-oxo-3-phenylpropan-2-ylamino}-3-oxo-1-phenylpropyl}-2-naphthamide
• 英文别名: N-[3-[[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-1-phenylpropyl]naphthalene-2-carboxamide
• CAS: 1609959-76-3
• 化学式: C₃₈H₄₁N₃O₅
• 分子量: 619.761
• InChiKey: ROTBJYKPNLYFIC-YGULHCKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  46
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  117
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (2S)-2-氨基-4-甲基-1-[(2R)-2-甲基环氧乙烷基]-1-戊酮 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 12.5h， 生成 N-{3-{(2S)-1-[(2S)-4-methyl-1-((2R)-2-methyloxiran-2-yl)-1-oxopentan-2-ylamino]-1-oxo-3-phenylpropan-2-ylamino}-3-oxo-1-phenylpropyl}-2-naphthamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel tripeptidyl epoxyketone derivatives constructed from β-amino acid as proteasome inhibitors

  摘要：

  A series of novel tripeptidyl epoxyketone derivatives constructed from beta-amino acid were designed, synthesized and evaluated as proteasome inhibitors. All target compounds were tested for their proteasome inhibitory activities and selected compounds were tested for their anti-proliferation activities against two multiple myeloma (MM) cell lines RPMI 8226 and NCI-H929. Among them, eleven compounds exhibited proteasome inhibitory rates of more than 50% at the concentration of 1 mu g/mL and nine compounds showed anti-proliferation activities with IC50 values at low micromolar level. Compound 20h displayed the most potent proteasome inhibitory activities (IC50: 0.11 +/- 0.01 mu M) and anti-proliferation activities with IC50 values at 0.23 +/- 0.01 and 0.17 +/- 0.02 mu M against two tested cell lines. Additionally, the poly-ubiquitin accumulation in the western blot analysis supported that proteasome inhibition in a cellular system was induced by compound 20h. All these experimental results confirmed that b-amino acid can be introduced as a building block for the development of proteasome inhibitors. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.011