N-((R)-3-(((S)-1-(((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3-oxo-1-phenylpropyl)-2-naphthamide | 1609959-85-4

• 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-((R)-3-(((S)-1-(((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3-oxo-1-phenylpropyl)-2-naphthamide
• 英文别名: N-[(1R)-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: 1609959-85-4
• 化学式: C₃₈H₄₁N₃O₅
• 分子量: 619.761
• InChiKey: ROTBJYKPNLYFIC-NDTOYMFRSA-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-((R)-3-(((S)-1-(((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-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

文献信息

• Modular Synthesis of Unnatural Peptides via Rh(III)-Catalyzed Diastereoselective Three-Component Carboamidation Reaction
  作者：Christopher W. Lamartina、Cassandra A. Chartier、Sumin Lee、Neel H. Shah、Tomislav Rovis

  DOI：10.1021/jacs.2c10793

  日期：2023.1.18

  substrate scope and is compatible with a wide array of protected amino acid residues that are utilized in Fmoc solid phase peptide synthesis. The methodology is applied to the synthesis of six diastereomeric proteasome inhibitor analogs, as well as the ligation of two 10-mer oligopeptides to construct a 21-mer polypeptide with an unnatural phenylalanine residue at the center.

  在此，我们报告了一种模块化肽连接方法，该方法在温和条件下，在 Rh(III) 催化的促进下，偶联二恶唑酮、芳基硼酸和丙烯酰胺，以非对映选择性方式构建酰胺键。通过将一个肽的 C 端转化为二恶唑酮，将第二个肽的 N 端转化为丙烯酰胺，这两部分可以通过芳基硼酸桥接，在连接点构建非天然苯丙氨酸、酪氨酸和色氨酸残基其相应的d -立体中心的非对映选择性。该反应表现出优异的官能团耐受性和较大的底物范围，并且与 Fmoc 固相肽合成中使用的各种受保护的氨基酸残基兼容。该方法适用于合成六种非对映体蛋白酶体抑制剂类似物，以及连接两个 10 聚体寡肽以构建中心具有非天然苯丙氨酸残基的 21 聚体多肽。
• Design, synthesis and biological evaluation of novel tripeptidyl epoxyketone derivatives constructed from β-amino acid as proteasome inhibitors
  作者：Jiankang Zhang、Jiayi Cao、Lei Xu、Yubo Zhou、Tao Liu、Jia Li、Yongzhou Hu

  DOI：10.1016/j.bmc.2014.04.011

  日期：2014.6

  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.