(2S)-2-[(2-benzyloxy-5-chloro-benzoyl)amino]-3-phenylpropanoic acid | 1469996-62-0

• 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: (2S)-2-[(2-benzyloxy-5-chloro-benzoyl)amino]-3-phenylpropanoic acid
• 英文别名: (2S)-2-[(5-chloro-2-phenylmethoxybenzoyl)amino]-3-phenylpropanoic acid
• CAS: 1469996-62-0
• 化学式: C₂₃H₂₀ClNO₄
• 分子量: 409.869
• InChiKey: GYSBWGOUYCPZIK-FQEVSTJZSA-N

物化性质

• 沸点：
  606.5±55.0 °C(Predicted)
• 密度：
  1.300±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S)-2-[(2-benzyloxy-5-chloro-benzoyl)amino]-3-phenylpropanoic acid 在 1-羟基苯并三唑一水物 、 水 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (2S)-2-({(2S)-2-[(2-benzyloxy-5-chloro-benzoyl)amino]3-phenyl-propanoyl}amino)-3-phenylpropanoic acid
  参考文献：
  名称：

  新型O-苄基水杨酰胺衍生物的合成及抗增殖活性

  摘要：

  背景：基于各种取代的水杨酰胺已显示出有趣的生物学特性，我们设计并合成了具有二肽部分的新的水杨酰胺衍生物。 方法：合成是基于目标分子的逐步构建并提供光学纯的化合物。 结论：测试了所得化合物对三种白血病细胞系的体外抗增殖作用，并在中等微摩尔范围内显示了GI50值。

  DOI：

  10.2174/1570180813666161020113827
• 作为产物：
  描述：

  L-苯丙氨酸盐酸盐 在 氯化亚砜 、 lithium hydroxide monohydrate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 33.25h， 生成 (2S)-2-[(2-benzyloxy-5-chloro-benzoyl)amino]-3-phenylpropanoic acid
  参考文献：
  名称：

  Substituted 2-hydroxy-N-(arylalkyl)benzamides induce apoptosis in cancer cell lines

  摘要：

  Variously substituted 2-hydroxy-N-(arylallcyl)benzamides were prepared and screened for anti-proliferative and cytotoxic activity in cancer cell lines in vitro. Five compounds, out of 33 showed single-digit micromolar IC50 values against several human cancer cell lines. One of the most potent compounds N-((R)-1-(4-chlorophenylcarbamoyl)-2-phenylethyl)-5-chloro-2-hydroxybenzamide (6k) reduced proliferation and induced apoptosis in the melanoma cell line G361 in a dose-dependent manner, as shown by decrease in 5-bromo-2'-deoxyuridine incorporation and increase in several apoptotic markers, including subdiploid population increase, activation of caspases and site-specific poly-(ADP-ribose)polymerase (PARP) cleavage. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.08.009

文献信息

• Synthesis and antiproteasomal activity of novel O -benzyl salicylamide-based inhibitors built from leucine and phenylalanine
  作者：Radek Jorda、Jan Dušek、Eva Řezníčková、Karel Pauk、Pratibha P. Magar、Aleš Imramovský、Vladimír Kryštof

  DOI：10.1016/j.ejmech.2017.04.027

  日期：2017.7

  and its inhibition by bortezomib showed benefit in clinical use for the treatment of multiple myeloma. We report here the library of antiproteasomal O-benzyl salicylamides built from leucine and phenylalanine. Prepared compounds displayed antiproliferative activity on K562, CEM and U266 cancer cell lines, ranging from high micromolar to submicromolar GI50 values. The most potent compounds (series 4 and

  抑制蛋白质降解是抑制癌细胞不受控制的增殖的策略之一。细胞中的蛋白水解降解主要通过蛋白酶体来确保，而硼替佐米的抑制作用在临床上用于治疗多发性骨髓瘤的治疗中显示出优势。我们在这里报告由亮氨酸和苯丙氨酸构建的抗蛋白酶体O-苄基水杨酰胺库。制备的化合物对K562，CEM和U266癌细胞系均具有抗增殖活性，从高微摩尔至亚微摩尔GI50值不等。进一步测定最有效的化合物（系列4和6）对U266细胞中26S蛋白酶体的胰凝乳蛋白酶样蛋白酶活性的抑制作用。大多数化合物在中等纳摩尔浓度（IC50为57至197 nM）时抑制蛋白酶体，并且与细胞效能有关。在基于细胞的测定中，绿色荧光蛋白（GFP）融合到被蛋白酶体迅速降解的短德格隆上，化合物诱导GFP的积累，并通过活细胞成像进行可视化和定量。还通过免疫印迹分析了用化合物4m处理的U266细胞中的多泛素化蛋白水平，发现了典型的高分子量泛素结合物涂片。最后，通过测量裂解
• Novel modified leucine and phenylalanine dipeptides modulate viability and attachment of cancer cells
  作者：Radek Jorda、Pratibha Magar、Denisa Hendrychová、Karel Pauk、Michal Dibus、Eliška Pilařová、Aleš Imramovský、Vladimír Kryštof

  DOI：10.1016/j.ejmech.2020.112036

  日期：2020.2

  Here, we describe the synthesis and biological characterization of 32 novel phenylalanine and leucine dipeptides modified on both the N and C termini by salicylic acid and aromatic or alicyclic amines, respectively. All compounds displayed anti proliferative activity in the tested cancer cell lines and eight of the compounds exhibited single digit micromolar GI(50) values. Treated cells rapidly detached from surface of tissue culture dishes and we found that focal adhesion kinase (FAK), p130CAS and paxillin, which are important regulators of cell adhesion, were dephosphorylated at Y397, Y410 and Y118, respectively. The most potent compound reduced proliferation in the HCT-116 cell line in a dose-dependent manner, as shown by a decrease in 5-bromo-2'-deoxyuridine incorporation into DNA. Furthermore, this compound increased the levels of several apoptotic markers, including activated caspases, and increased site-specific poly-(ADP-ribose)polymerase (PARP) cleavage. (C) 2020 Elsevier Masson SAS. All rights reserved.
• Substituted 2-hydroxy-N-(arylalkyl)benzamides induce apoptosis in cancer cell lines
  作者：Aleš Imramovský、Radek Jorda、Karel Pauk、Eva Řezníčková、Jan Dušek、Jiří Hanusek、Vladimír Kryštof

  DOI：10.1016/j.ejmech.2013.08.009

  日期：2013.10

  Variously substituted 2-hydroxy-N-(arylallcyl)benzamides were prepared and screened for anti-proliferative and cytotoxic activity in cancer cell lines in vitro. Five compounds, out of 33 showed single-digit micromolar IC50 values against several human cancer cell lines. One of the most potent compounds N-((R)-1-(4-chlorophenylcarbamoyl)-2-phenylethyl)-5-chloro-2-hydroxybenzamide (6k) reduced proliferation and induced apoptosis in the melanoma cell line G361 in a dose-dependent manner, as shown by decrease in 5-bromo-2'-deoxyuridine incorporation and increase in several apoptotic markers, including subdiploid population increase, activation of caspases and site-specific poly-(ADP-ribose)polymerase (PARP) cleavage. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Synthesis and Antiproliferative Activities of Novel O-Benzyl Salicylamide Derivatives
  作者：Jan Dusek、Ales Imramovsky、Karel Pauk、Radek Jorda、Eva Reznickova、Vladimir Krystof

  DOI：10.2174/1570180813666161020113827

  日期：2017.6.6

  Background: On the basis that various substituted salicylamides have shown interesting biological properties, we designed and synthesized new salicylamide derivatives with dipeptide moieties. Methods: The synthesis was based on the gradual building of target molecules and provided optically pure compounds. Conclusion: The obtained compounds were tested for their antiproliferative effect against three

  背景：基于各种取代的水杨酰胺已显示出有趣的生物学特性，我们设计并合成了具有二肽部分的新的水杨酰胺衍生物。 方法：合成是基于目标分子的逐步构建并提供光学纯的化合物。 结论：测试了所得化合物对三种白血病细胞系的体外抗增殖作用，并在中等微摩尔范围内显示了GI50值。