1-phenyl-2,6,6-trimethyl-4,5,6,7-tetrahydroindol-4-one | 57663-14-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-phenyl-2,6,6-trimethyl-4,5,6,7-tetrahydroindol-4-one
• 英文别名: 2,6,6-Trimethyl-1-phenyl-6,7-dihydro-1H-indol-4(5H)-one；2,6,6-trimethyl-1-phenyl-5,7-dihydroindol-4-one
• CAS: 57663-14-6
• 化学式: C₁₇H₁₉NO
• 分子量: 253.344
• InChiKey: DGMKAUAWYOJTDJ-UHFFFAOYSA-N

物化性质

• 熔点：
  135-137 °C
• 沸点：
  401.7±24.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  22
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-phenyl-2,6,6-trimethyl-4,5,6,7-tetrahydroindol-4-one 在 磷酸酐 、 sodium hydroxide 、 磷酸 、 盐酸羟胺 作用下， 以 乙醇 、 水 为溶剂， 反应 4.0h， 生成 6H-1-phenyl-2,7,7-trimethyl-4,5,7,8-tetrahydropyrrolo[3,2-c]azepin-4-one
  参考文献：
  名称：

  Tetrahydropyrrolo[3,2-c]azepin-4-ones as a new class of cytotoxic compounds

  摘要：

  Pyrroloazepinones 8a-j and 9a-j were designed by structural modification of lead compound 3. These compounds were tested on five tumor cell lines to determine the role of the azeto ring and the 2-methyl substituent in the cytotoxicity of compound 3. Our results show that compounds 8a-j (R-1 = CH3) have dramatically reduced cytotoxicity, resulting from the loss of the azeto moiety of lead compound 3. By contrast, azepinones 9a-j (R-1 = 4-nitrophenyl) inhibited the proliferation of almost all cancer cell lines tested even though they lack the azeto ring. Preliminary SAR studies with these compounds revealed the importance of halogens at the para- or meta-position of the 1-phenyl moiety. Additionally, derivatives 9a (R-2 = H), 9e (R-2 = 4-F), and 9g (R-2 = 4-OMe) were selectively cytotoxic to U-251 cells. However, none of the pyrroloazepinones inhibited the enzymatic activity of CDK1/cyclin B, CDK5/p25, and GSK-3. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.02.012
• 作为产物：
  描述：

  6,6-dimethyl-4-oxo-1-phenyl-4,5,6,7-tetrahydroindole-2-acetic acid 反应 0.5h， 以72%的产率得到1-phenyl-2,6,6-trimethyl-4,5,6,7-tetrahydroindol-4-one
  参考文献：
  名称：

  Nagarajan, Kuppuswamy; Talwalker, Purnachard K.; Goud, A. Nagana, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1988, vol. 27, # 1-12, p. 1113 - 1123

  摘要：

  DOI：

文献信息

• <i>De Novo</i> Design of Non-coordinating Indolones as Potential Inhibitors for Lanosterol 14-α-Demethylase (CYP51)
  作者：Rodolfo González-Chávez、Roberto Martínez、María Eugenia Torre-Bouscoulet、Marco Gallo、Marco Martín González-Chávez

  DOI：10.1248/cpb.c13-00003

  日期：——

  The development of antifungal drugs that inhibit lanosterol 14-α-demethylase (CYP51) via non-covalent ligand interactions is a strategy that is gaining importance. A series of novel tetraindol-4-one derivatives with 1- and 2-(2,4-substituted phenyl) side chains were designed and synthesized based on the structure of CYP51 and fluconazole. The antifungal activities of these derivatives against eight human pathogenic filamentous fungi and yeast strains were evaluated in vitro by measuring the minimal inhibitory concentrations. Nearly all tested compounds 8a–g displayed activity against Candida tropicalis, Candida guilliermondii and Candida parapsilosis with a minimum inhibitory concentration (MIC) value until 8 µg mL−1, on the other hand compounds 7a–g showed activity against Aspergillus fumigatus with a MIC value of 31.25 µg mL−1. A molecular modeling study of the binding interactions between compounds 6, 7d, 8g and the active site of MtCYP51 was conducted based on the computational docking results.

  通过非共价配体相互作用抑制羊毛甾醇14α-去甲基酶（CYP51）的抗真菌药物的开发策略正变得越来越重要。基于CYP51和氟康唑的结构，设计并合成了一系列含有1-和2-(2,4-取代苯基)侧链的新型四吲哚-4-酮衍生物。通过测定最小抑制浓度，对这些衍生物针对八种人类病原性丝状真菌和酵母菌株的体外抗真菌活性进行了评估。几乎所有测试的化合物8a-g都对热带念珠菌、季也蒙念珠菌和副念珠菌显示活性，最小抑制浓度（MIC）值高达8μg mL^-1，另一方面，化合物7a-g对烟曲霉显示活性，MIC值为31.25μg mL^-1。基于计算对接结果，进行了化合物6、7d、8g与MtCYP51活性位点的结合相互作用的分子建模研究。
• Synthesis of new fused dipyrroloazepinones via a two-step tandem reaction: Comparison of the Schmidt and Beckmann pathways
  作者：Francisco Xavier Domínguez-Villa、Gustavo Ávila-Zárraga、Concepción Armenta-Salinas

  DOI：10.1016/j.tetlet.2020.151751

  日期：2020.4

  A new set of polyheterocyclic compounds (4,7,7-trimethyl-5-aryl-7a,8,9,10-tetrahydrodipyrrolo[3,2-c;2',1'-g]azepin-2-ones) was synthesized via a tandem process involving a Beckmann rearrangement followed by a cyclization between the nitrogen atom and primary halide fragment. Ring expansion from 6 to 7 members and the fusion of the resulting ring with a five-membered ring took place in just one process

  一组新的多杂环化合物（4,7,7-三甲基-5-芳基-7a，8,9,10-四氢二吡咯并[3,2-c; 2'，1'-g] azepin-2-ones）是通过涉及贝克曼重排的串联过程合成，然后在氮原子和伯卤化物片段之间环化。环从6个扩环到7个环，并将生成的环与5元环融合在一起仅需一个过程。
• Synthesis, molecular docking, and in silico ADME/Tox profiling studies of new 1-aryl-5-(3-azidopropyl)indol-4-ones: Potential inhibitors of SARS CoV-2 main protease
  作者：Francisco Xavier Domínguez-Villa、Noemi Angeles Durán-Iturbide、José Gustavo Ávila-Zárraga

  DOI：10.1016/j.bioorg.2020.104497

  日期：2021.1

  and showed them to be potential inhibitors of the SARS CoV-2 main protease (3CLpro). The compounds were obtained in good overall yields and molecular docking indicated favorable binding with 3CLpro. In silico ADME/Tox profile of the new compounds were calculated using the SwissADME and pkCSM-pharmacokinetics web tools, and indicated adequate values of absorption, distribution and excretion, features

  引起呼吸道感染 COVID-19 的病毒 SARS CoV-2 继续在世界范围内传播，迄今为止已导致超过一百万人死亡。尽管 COVID-19 疫苗的开发似乎进展迅速，但科学家们仍在继续寻找不同的治疗方案来治疗这种新疾病。在这项工作中，我们合成了五种新的 1-芳基-5-(3-叠氮基丙基)吲哚-4-酮，并证明它们是 SARS CoV-2 主要蛋白酶 (3CLpro) 的潜在抑制剂。这些化合物以良好的总收率获得，分子对接表明与 3CLpro 具有良好的结合。使用SwisSADME和pkCSM 药代动力学网络工具计算新化合物的计算机ADME/Tox 概况，并显示吸收、分布和排泄的足够值以及与生物利用度相关的特征。此外，这些化合物的毒性值较低。还根据 Lipinski 和 Veber 规则预测了化合物的药物相似水平。
• Unusual Sulfonation of 1-(4-R-Phenyl)-2.6,6-trimethyl-4-oxo-4,5,6,7-tetrahydroindoles Under Schmidt Conditions
  作者：Roberto Martínez、Gustavo Avila、Eduardo Reyes

  DOI：10.1080/00397919508012669

  日期：1995.4

  Abstract Unexpected 4-oxo-tetrahydroindoles 3-sulfonic acids were synthesized from their corresponding 4-oxo-tetrahydroindoles using sodium azide and sulfuric acid (Schmidt conditions).

  摘要 意外的 4-氧-四氢吲哚 3-磺酸是使用叠氮化钠和硫酸（施密特条件）从其相应的 4-氧-四氢吲哚合成的。
• RAMADAS S. R.; PADMANABHAN S., CURR. SCI. (INDIA), 1979, 48, NO 2, 52-53
  作者：RAMADAS S. R.、 PADMANABHAN S.

  DOI：——

  日期：——