(S)-methyl 2-((S)-4-methyl-2-(pyrazine-2-carboxamido)pentanamido)-3-(naphthalen-2-yl) propanoate | 1194235-06-7

• 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: (S)-methyl 2-((S)-4-methyl-2-(pyrazine-2-carboxamido)pentanamido)-3-(naphthalen-2-yl) propanoate
• 英文别名: N-pyrazineformyl-L-leucyl-3-naphth-2-ylalanine methyl ester
• CAS: 1194235-06-7
• 化学式: C₂₅H₂₈N₄O₄
• 分子量: 448.522
• InChiKey: OJFQTIFGNOEOTH-SFTDATJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.67
• 重原子数：
  33.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  110.28
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (S)-methyl 2-((S)-4-methyl-2-(pyrazine-2-carboxamido)pentanamido)-3-(naphthalen-2-yl) propanoate 在 1-羟基苯并三唑 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 1.17h， 生成
  参考文献：
  名称：

  脯氨酸硼酸类化合物及其制备方法和用途

  摘要：

  本发明提供了具有下述式(I)所示结构的化合物或其盐。该化合物是脯氨酸硼酸类蛋白酶体抑制剂化合物，具有良好的蛋白酶体抑制活性和优异的成药性。

  公开号：

  CN108929340B
• 作为产物：
  描述：

  2-甲酸吡嗪 在 1-羟基苯并三唑 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.09h， 生成 (S)-methyl 2-((S)-4-methyl-2-(pyrazine-2-carboxamido)pentanamido)-3-(naphthalen-2-yl) propanoate
  参考文献：
  名称：

  脯氨酸硼酸类化合物及其制备方法和用途

  摘要：

  本发明提供了具有下述式(I)所示结构的化合物或其盐。该化合物是脯氨酸硼酸类蛋白酶体抑制剂化合物，具有良好的蛋白酶体抑制活性和优异的成药性。

  公开号：

  CN108929340B

文献信息

• Synthesis and biological activity of peptide proline-boronic acids as proteasome inhibitors
  作者：Liqiang Han、Yanzhao Wen、Ridong Li、Bo Xu、Zemei Ge、Xin Wang、Tieming Cheng、Jingrong Cui、Runtao Li

  DOI：10.1016/j.bmc.2017.05.049

  日期：2017.8

  and proteasome inhibition against three subunits. The results indicated that series II have much better biological activities than series I. The compound II-7 exhibited not only excellent biological activities with IC50 values of nM level in both cell and proteasome models, but also much better subunit selectivity. Thus, proline-boronic acid as warhead is reasonable in the design of proteasome inhibitors

  基于脯氨酸硼酸作为药效基团在激酶抑制剂中的应用以及我们先前的研究结果，以脯氨酸硼酸为战斗部，使用了两个系列的肽脯氨酸硼酸，二肽脯氨酸硼酸（I）和三肽设计并合成了脯氨酸硼酸（II）。首先评估所有合成的化合物对MGC803细胞的生物学活性，然后选择最佳的化合物II-7来测试其在六种人类肿瘤细胞系上的抗肿瘤谱以及对三个亚基的蛋白酶体抑制作用。结果表明，系列II具有比系列I更好的生物学活性。化合物II-7在细胞和蛋白酶体模型中不仅表现出优异的生物学活性（IC 50值为nM），而且亚单位选择性也好得多。因此，脯氨酸硼酸作为战斗部在蛋白酶体抑制剂的设计中是合理的。
• Design, synthesis and biological evaluation of tripeptide boronic acid proteasome inhibitors
  作者：Yongqiang Zhu、Shuyang Yao、Bo Xu、Zemei Ge、Jingrong Cui、Tieming Cheng、Runtao Li

  DOI：10.1016/j.bmc.2009.08.023

  日期：2009.10

  A series of tripeptide boronate proteasome inhibitors were designed and synthesized on the basis of our previously built tripeptide aldehyde 3D-QSAR models. All the synthesized compounds were evaluated for their proteasome-inhibitory activities in an isolated 20S rabbit proteasome, and selected compounds were evaluated for their antitumor activities in vitro against four human cancer cell lines. Biological results showed bulky and negative substituents at P-2 position improved the proteasome-inhibitory potency obviously, which completely conformed to the theoretical models, while those at P-3 position thoroughly deviated from the 3D-QSAR model. Most of the screened compounds showed less than 1 nM inhibitory potency and high selectivity against 20S proteasome, of which 7f is the most potent (IC50 = 0.079 nM) and twofold more active than bortezomib (IC50 = 0.161 nM). Cell viability indicated hydrophilic 4-hydroxyphenyl substituent at P-2 or P-3 position was not favorable to the cellular activities. Especially for the two hematologic cancer cell lines, HL-60 and U266, 7f inhibited them at the level of less than 10 nM and was more potent than the control bortezomib. It is being considered a promising new lead to be developed for the treatment of various cancers. (C) 2009 Elsevier Ltd. All rights reserved.