1-苯甲酰吲哚-3-甲醛 | 27092-42-8

• 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
• 中文名称: 1-苯甲酰吲哚-3-甲醛
• 英文名称: 1-benzoylindole-3-carboxaldehyde
• 英文别名: 1-benzoyl-1H-indole-3-carbaldehyde；N-benzoylindole-3-carbaldehyde；N-benzoyl-1H-indole-3-carbaldehyde；1-benzoyl-indole-3-carbaldehyde；1-benzoylindole-3-carbaldehyde
• CAS: 27092-42-8
• 化学式: C₁₆H₁₁NO₂
• 分子量: 249.269
• InChiKey: QMNJJAQYGLNGGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  39.1
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  1-苯甲酰吲哚-3-甲醛 在 palladium diacetate 、 N-氟代双苯磺酰胺 、 聚甘氨酸 、 copper dichloride 作用下， 以71%的产率得到1-benzoyl-4-chloro-1H-indole-3-carbaldehyde
  参考文献：
  名称：

  Pd(II)-催化的瞬态定向基团辅助的区域选择性不同 C4-H 官能化吲哚

  摘要：

  开发一种合理的策略来实现吲哚的位点选择性 C4-H 卤化是一项有吸引力但具有挑战性的任务。在此，我们公开了一种 Pd(II) 催化的瞬态导向基团 (TDG) 辅助方法，用于实现吲哚的 C4 氯化/溴化，采用甘氨酸作为 TDG，NFSI 作为备用氧化剂。使用廉价且市售的 CuX 2作为卤化物源是该协议的主要亮点。此外，TDG 方法还扩展到使用乙酸作为乙酸盐源和 1-fluoro-2,4,6-trimethylpyridinium triflate 作为氧化剂的 C4 乙酰氧基化吲哚。

  DOI：

  10.1021/acs.orglett.2c00320
• 作为产物：
  描述：

  在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 1-苯甲酰吲哚-3-甲醛
  参考文献：
  名称：

  Moriya, Tamon; Hagio, Katsuaki; Yoneda, Naoto, Chemical and pharmaceutical bulletin, 1980, vol. 28, # 6, p. 1711 - 1721

  摘要：

  DOI：

文献信息

• Synthesis, Molecular Docking and Biological Evaluation of Novel Flavone Derivatives as Potential Anticancer Agents Targeting Akt
  作者：Heba M. Abo-Salem、Abdullah A Gibriel、Mohamed E. El Awady、Adel H. Mandour

  DOI：10.2174/1573406416666200306115035

  日期：2020.12.30

  Flavonoids are naturally occurring compounds with versatile healthpromoting effects against various diseases.

  This aim of this paper is to synthesize and evaluate the biological activity of novel flavone derivatives against cancer.

  A new series of 2-hydroxy-α,β-unsaturated ketones 2a-h, was synthesized via the reaction of N-substituted-indole-3-carboxaldehyde 1a-h with 2-hydroxy acetophenone in the presence of piperidine. The oxidative cyclization of 2a-h using hydrogen peroxide/KOH and/or dimethyl sulfoxide/I2 produced the corresponding 2-(N-substituted-1H-indol-3-yl)-3-hydroxy-4H-chromen- 4-ones 3a-h and 2-(N-substituted-1H-indol-3-yl)-4H-chromen-4-ones 4a-h, respectively. Antiproliferative activities for synthesized series were investigated against HCT-116 colon and MCF- 7 breast cancer cell lines. Molecular downstream effects were evaluated using RT-PCR. Moreover, molecular docking was carried out to pinpoint the binding mode of the most active compounds into the active site of Akt enzyme (PDB ID: 3QKK).

  All compounds exhibited an anti-proliferative activity range of 52-97% and 67.2-99% against HCT-116 and MCF-7, respectively. Compounds 3b, 3h, 3g and 4h had a minimal inhibitory effect on normal BJ1 cells indicating their safety profile. Compounds 3b and 4h, in particular, exhibited the most potent antiproliferative activity against HCT116 and MCF7, meanwhile compounds 3g, 3h and 4g showed potent to moderate activity. Compound 3b had IC50 of 78.3 μM and 53.9 μM against HCT-116 and MCF-7 respectively with comparable IC50 for doxorubicin of 65.1 μM and 45.02 μM. Compound 3b exhibited significant down-regulation for Akt and significant up-regulation of CAS9 and CDKN1genes in all tested cell lines.

  The synthesized flavone derivatives and particularly compound 3b exhibited promising anticancer activity through Akt inhibition.

  背景：黄酮类化合物是天然存在的化合物，具有多种对抗各种疾病的促进健康的效果。 目标：本文的目的是合成和评估新型黄酮衍生物对癌症的生物活性。 方法：通过N-取代吲哚-3-甲醛1a-h与2-羟基苯乙酮在哌啶存在下反应合成了一系列新的2-羟基-α，β-不饱和酮2a-h。使用过氧化氢/KOH和/或二甲基亚砜/I2对2a-h进行氧化环化反应，分别产生相应的2-(N-取代-1H-吲哚-3-基)-3-羟基-4H-香豆素-4-酮3a-h和2-(N-取代-1H-吲哚-3-基)-4H-香豆素-4-酮4a-h。对合成系列的抗增殖活性进行了对HCT-116结肠癌和MCF-7乳腺癌细胞系的研究。使用RT-PCR评估了分子下游效应。此外，进行了分子对接以确定最活跃化合物与Akt酶的活性位点(PDB ID: 3QKK)的结合方式。 结果：所有化合物对HCT-116和MCF-7表现出52-97%和67.2-99%的抗增殖活性。化合物3b、3h、3g和4h对正常BJ1细胞的抑制作用最小，表明它们的安全性良好。特别是化合物3b和4h对HCT116和MCF7表现出最强的抗增殖活性，同时化合物3g、3h和4g表现出强到中等的活性。化合物3b在HCT-116和MCF-7中的IC50分别为78.3μM和53.9μM，与多柔比星的IC50相当，分别为65.1μM和45.02μM。化合物3b在所有测试的细胞系中显著下调Akt，并显著上调CAS9和CDKN1基因。 结论：合成的黄酮衍生物，特别是化合物3b，通过抑制Akt表现出有希望的抗癌活性。
• Transient Directing Group Strategy as a Unified Method for Site Selective Direct C4–H Halogenation of Indoles
  作者：Guanghua Kuang、Dandan Liu、Xuerong Chen、Guangyuan Liu、Yang Fu、Yiyuan Peng、Hua Li、Yirong Zhou

  DOI：10.1021/acs.orglett.1c03131

  日期：2021.11.5

  A unified method for direct C4–H halogenation of indoles has been accomplished with the assistance of anthranilic acids as suitable transient directing groups. Exclusive site selectivity (one out of five potential reactive sites) as well as good functional group tolerance was obtained to install three kinds of halogen atoms (Cl, Br and I, respectively) by using inexpensive N-halosuccinimides (NXS)

  在邻氨基苯甲酸作为合适的瞬态导向基团的帮助下，实现了吲哚直接 C4-H 卤化的统一方法。通过使用廉价的N-卤代琥珀酰亚胺 (NXS) 作为卤素源，在以下条件下获得了独家的位点选择性（五分之一的潜在反应位点）以及良好的官能团耐受性来安装三种卤素原子（分别为 Cl、Br 和 I）条件温和。利用产物中丰富的官能团，通过一步后期推导，轻松构建了多种含氮杂环。
• Synthesis and evaluation of indole, pyrazole, chromone and pyrimidine based conjugates for tumor growth inhibitory activities – Development of highly efficacious cytotoxic agents
  作者：Palwinder Singh、Matinder Kaur、Wolfgang Holzer

  DOI：10.1016/j.ejmech.2010.08.004

  日期：2010.11

  chromone-pyrazole, indole-pyrimidine, indole-indolinone and indole-pyrazole moieties. Evaluation of these compounds for tumor growth inhibitory activities over 60 human tumor cell lines provided highly efficacious compounds 15, 41, 43, 66, 69, and 72 with an average GI50 over all the 60 human tumor cell lines as 3.2 μM, 3.1 μM, 1.7 μM, 2.6 μM, 50.1 μM and 2.0 μM, respectively.

  基于先导化合物10和11，通过色酮-嘧啶，色酮-吲哚满酮，色酮-吡唑，吲哚-嘧啶，吲哚-吲哚满酮和吲哚-吡唑部分的组合合成了许多缀合物。这些化合物的肿瘤生长抑制活性超过60人类肿瘤细胞系提供的评价是高度有效的化合物15，41，43，66，69，和72，平均GI 50在所有60个人肿瘤细胞系为3.2μM，3.1μM分别为1.7μM，2.6μM，50.1μM和2.0μM。
• Synthesis of vinylindoles and vinylpyrroles by the Peterson olefination or by use of the Nysted reagent
  作者：Wayland E. Noland、Christopher L. Etienne、Nicholas P. Lanzatella

  DOI：10.1002/jhet.313

  日期：2011.3

  Vinylindoles and vinylpyrroles were prepared from their corresponding aldehydes or ketones using the Peterson olefination, or by use of the Nysted reagent, a commercially available gem‐dimetallic compound. The two methods provide efficient and convenient access to these useful heterocyclic 1,3‐diene systems. J. Heterocyclic Chem., (2011).

  乙烯基吲哚和乙烯基吡咯是使用Peterson烯烃或相应的市售宝石-双金属化合物Nysted试剂，由其相应的醛或酮制得的。两种方法可有效便捷地访问这些有用的杂环1,3-二烯系统。J.杂环化​​学。（2011）。
• A Catalytic Antibody Programmed for Torsional Activation of Amide Bond Hydrolysis
  作者：Ranjana Aggarwal、Fabio Benedetti、Federico Berti、Sabrina Buchini、Alfonso Colombatti、Francesca Dinon、Vinicio Galasso、Stefano Norbedo

  DOI：10.1002/chem.200204620

  日期：2003.7.7

  transition state for hydrolysis of a distorted amide, accelerates the hydrolysis of the corresponding amides 1 a-3 a by a factor of 10(3) at pH 8. The mechanisms of both the uncatalyzed and antibody-catalyzed reactions were studied. Between pH 8 and 12 the uncatalyzed hydrolysis of N-toluoylindoles 1 a and 3 a shows a simple first-order dependence on [OH(-)], while hydrolysis of 3 a is zeroth-order

  针对磺酰胺半抗原4a获得的酰胺酶抗体312d6（模仿扭曲的酰胺水解的过渡态）在pH 8时将相应酰胺1a-3a的水解速度提高了10（3）倍。研究了未催化反应和抗体催化反应。在pH 8和12之间，N-toluoylindoles 1a和3a的未催化水解显示出对[OH（-）]的简单一阶依赖性，而在pH低于[OH（-）]时3a的水解为零阶。 8.由于两性离子与pK（a）9.74分解为阴离子，因此相应色氨酸酰胺2a水解的pH分布更为复杂。两性离子的水解和阴离子形式的2a都显示出对[OH（-）]的简单一阶依赖性。H（2）（18）O /（18）OH（-）与底物之间不存在（18）O交换，1 a（k（H）/ k（D）= 1.12）和3 a（k（H）/ k（D）= 1.24）的正常SKIE以及用于p-取代水解的Hammett常数rho值酰胺3ae与酯样机理一致，其中四面体中间体的形成决定速率，而胺以阴离子形式离去。研究了312d6催化的3