methyl 4-(3-phenyl-1H-indol-2-yl)benzoate | 1171122-83-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: methyl 4-(3-phenyl-1H-indol-2-yl)benzoate
• CAS: 1171122-83-0
• 化学式: C₂₂H₁₇NO₂
• 分子量: 327.382
• InChiKey: SUVDWLLYJRUDFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  42.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl 4-(3-phenyl-1H-indol-2-yl)benzoate 在 偶氮二甲酸二异丙酯 、 三苯基膦 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 6.5h， 生成 2-(2-(2-hydroxyethoxy)ethoxy)ethyl 4-(3-phenyl-1H-indol-2-yl)benzoate
  参考文献：
  名称：

  A synthetic 2,3-diarylindole induces microtubule destabilization and G2/M cell cycle arrest in lung cancer cells

  摘要：

  The anticancer potential of a synthetic 2,3-diarylindole (PCNT13) has been demonstrated in A549 lung cancer cells by inducing both apoptosis and autophagic cell death. In this report, we designed to connect a fluorophore to the compound via a hydrophilic linker for monitoring intracellular localization. The best position for linker attachment was identified from cytotoxicity and effect on cell morphology of newly synthesized PCNT13 derivatives bearing hydrophilic linker. Cytotoxicity and effect on cell morphology related to the parental compound were used to identify the optimum position for linker attachment in the PCNT13 chemical structure. The fluorophore-PCNT13 conjugate was found to localize in the cytoplasm. Microtubules were found to be one of the cytosolic target proteins of PCNT13, as the compound could inhibit tubulin polymerization in vitro. A molecular docking study revealed that PCNT13 binds at the colchicine binding site on the alpha/beta-tubulin heterodimer. The effect of PCNT13 on microtubule dynamics caused cell cycle arrest in the G2/M phase as analyzed by flow cytometric analysis.

  DOI：

  10.1016/j.bmcl.2019.126777
• 作为产物：
  描述：

  在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以74 mg的产率得到methyl 4-(3-phenyl-1H-indol-2-yl)benzoate
  参考文献：
  名称：

  由氨基苄基Ph盐柔性合成2，3-二取代的吲哚。芸香根碱的直接合成

  摘要：

  取代的（2-氨基苄基）三苯基phosph溴化物与芳族醛或α，β-不饱和醛的反应构成了高产率的2,3-二取代的吲哚的新合成。4-氧代-3,4-二氢喹唑啉-2-甲醛的加合物是几种芸苔芸香碱合成中的高级中间体。

  DOI：

  10.1021/jo900718g

文献信息

• Dissecting the Electronic Contribution to the Regioselectivity of the Larock Heteroannulation Reaction in the Oxidative Addition and Carbopalladation Steps
  作者：Kanyapat Yiamsawat、Kevin P. Gable、Pitak Chuawong

  DOI：10.1021/acs.joc.1c02560

  日期：2022.1.21

  the regiochemical outcome of the reaction. Density functional theory calculations of the oxidative addition and carbopalladation steps revealed the electronic influences of the substituted 2-iodoaniline derivatives toward the overall rate of the reaction. In contrast, the electronic properties of the asymmetric diarylacetylene remained the critical product-determining factor of regioselectivity.

  制备了取代的 2-碘苯胺衍生物并将其用作反应物，与不对称二芳基乙炔一起，通过 Larock 杂环化反应合成一系列 6-取代的 2,3-二芳基吲哚衍生物。2-碘苯胺衍生物上的给电子取代基阻碍了反应，而吸电子取代基则完全转化为吲哚产物。此外，取代的2-碘苯胺反应物的电子性质对区域选择性没有影响。相反，不对称二芳基乙炔的电子效应显着影响反应的区域化学结果。氧化加成和碳钯化步骤的密度泛函理论计算揭示了取代的 2-碘苯胺衍生物对反应总速率的电子影响。相比之下，不对称二芳基乙炔的电子特性仍然是区域选择性的关键产物决定因素。
• Regioselectivity of Larock Heteroannulation: A Contribution from Electronic Properties of Diarylacetylenes
  作者：Nared Phetrak、Thanya Rukkijakan、Jakkapan Sirijaraensre、Samran Prabpai、Palangpon Kongsaeree、Chayada Klinchan、Pitak Chuawong

  DOI：10.1021/jo402304s

  日期：2013.12.20

  A series of 2,3-diarylindoles were synthesized from 2-iodoaniline and unsymmetrical diarylacetylenes using the Larock heteroannulation. Diarylacetylenes bearing electron-withdrawing substituents lead to 2,3-diarylindoles with substituted phenyl moieties at the 2-position as major products, while those with electron-donating groups preferably yield indole products with substituted phenyl moieties at the 3-position. The regioisomeric product ratios exhibit a clear correlation with Hammett sigma(p) values. DFT calculations reveal the origin of this effect, displaying smaller activation energy barriers for those pathways leading to the major regioisomer.
• A synthetic 2,3-diarylindole induces cell death via apoptosis and autophagy in A549 lung cancer cells
  作者：Thanya Rukkijakan、Lukana Ngiwsara、Kriengsak Lirdprapamongkol、Jisnuson Svasti、Nared Phetrak、Pitak Chuawong

  DOI：10.1016/j.bmcl.2016.03.079

  日期：2016.5

  A series of 2,3-diarylindoles were synthesized via the Larock heteroannulation, and evaluated for their anticancer activity against A549 lung cancer cells. The most potent compound, PCNT13 with IC50 = 5.17 mu M, caused the induction of two modes of programmed cell death, apoptosis and autophagy. (C) 2016 Elsevier Ltd. All rights reserved.
• A synthetic 2,3-diarylindole induces microtubule destabilization and G2/M cell cycle arrest in lung cancer cells
  作者：Bongkotrat Thanaussavadate、Lukana Ngiwsara、Kriengsak Lirdprapamongkol、Jisnuson Svasti、Pitak Chuawong

  DOI：10.1016/j.bmcl.2019.126777

  日期：2020.1

  The anticancer potential of a synthetic 2,3-diarylindole (PCNT13) has been demonstrated in A549 lung cancer cells by inducing both apoptosis and autophagic cell death. In this report, we designed to connect a fluorophore to the compound via a hydrophilic linker for monitoring intracellular localization. The best position for linker attachment was identified from cytotoxicity and effect on cell morphology of newly synthesized PCNT13 derivatives bearing hydrophilic linker. Cytotoxicity and effect on cell morphology related to the parental compound were used to identify the optimum position for linker attachment in the PCNT13 chemical structure. The fluorophore-PCNT13 conjugate was found to localize in the cytoplasm. Microtubules were found to be one of the cytosolic target proteins of PCNT13, as the compound could inhibit tubulin polymerization in vitro. A molecular docking study revealed that PCNT13 binds at the colchicine binding site on the alpha/beta-tubulin heterodimer. The effect of PCNT13 on microtubule dynamics caused cell cycle arrest in the G2/M phase as analyzed by flow cytometric analysis.
• A Flexible Synthesis of 2,3-Disubstituted Indoles from Aminobenzyl Phosphonium Salts. A Direct Synthesis of Rutaecarpine
  作者：George A. Kraus、Haitao Guo

  DOI：10.1021/jo900718g

  日期：2009.8.7

  substituted (2-aminobenzyl)triphenylphosphonium bromides with aromatic aldehydes or α,β-unsaturated aldehydes constitutes a new synthesis of 2,3-disubstitued indoles in high yields. The adduct from 4-oxo-3,4-dihydroquinazoline-2-carbaldehyde was an advanced intermediate in the synthesis of several rutaecarpines.

  取代的（2-氨基苄基）三苯基phosph溴化物与芳族醛或α，β-不饱和醛的反应构成了高产率的2,3-二取代的吲哚的新合成。4-氧代-3,4-二氢喹唑啉-2-甲醛的加合物是几种芸苔芸香碱合成中的高级中间体。