(4-methyl-1H-indol-1-yl)(phenyl)methanone | 30933-68-7

• 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: (4-methyl-1H-indol-1-yl)(phenyl)methanone
• 英文别名: N-benzoyl-4-methylindole；(4-Methylindol-1-yl)-phenylmethanone
• CAS: 30933-68-7
• 化学式: C₁₆H₁₃NO
• 分子量: 235.285
• InChiKey: SAMUOITWFIEYSN-UHFFFAOYSA-N

物化性质

• 沸点：
  327.4±25.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 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：

  (4-methyl-1H-indol-1-yl)(phenyl)methanone 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 potassium carbonate 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 14.0h， 生成 2-(4-((2-butyl-5-nitro-1H-benzo[d]imidazol-1-yl)methyl)-1H-indol-1-yl)benzonitrile
  参考文献：
  名称：

  Design, synthesis and biological evaluation of new 5-nitro benzimidazole derivatives as AT1 antagonists with anti-hypertension activities

  摘要：

  The design, synthesis, in vitro and in vivo evaluation of 5-nitro benzimidazole with 1,4-disubsituted or 1,5-disubsituted indole derivatives as novel angiotensin II receptor antagonist is outlined. Radioligand binding assays showed that 2-(4-((2-butyl-5-nitro-1H-benzo[d] imidazol-1-yl) methyl)-1H-indol-1-yl) benzoic acid, compound 3, displayed a high affinity for the angiotensin II type 1 receptor with IC50 value of 1.03 +/- 0.26 nM. The biological evaluation on spontaneously hypertensive rats and renal hypertensive rats showed that 3 could cause significant decrease on MBP in a dose dependent manner, whose maximal response lowered 30 mmHg of MBP at 5 mg/kg and 41 mmHg of MBP at 10 mg/kg after oral administration, and the significant antihypertensive effect lasted beyond 24 h, which is better than Losartan. Taken together 3 could be considered as an effective and durable anti-hypertension drug candidate. These encouraging results are deserved of further investigation towards its use for therapeutic benefit. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.02.008
• 作为产物：
  描述：

  4-甲基吲哚 、 苯甲酰氯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (4-methyl-1H-indol-1-yl)(phenyl)methanone
  参考文献：
  名称：

  N-苯基吲哚衍生物作为具有抗高血压活性的AT拮抗剂：设计，合成和生物学评估。

  摘要：

  概述了以1、4-二取代或1,5-二取代的吲哚衍生物作为新型血管紧张素II受体拮抗剂的6-取代苯并咪唑的设计，合成，体外和体内评价。放射性配体结合测定表明，几种6-取代的苯并咪唑衍生物以与替米沙坦相同的数量级显示出与血管紧张素II 1型受体的高亲和力结合。对自发性高血压大鼠的生物学评估显示，2- [4-[[2-n-丙基-4-甲基-6-（1-甲基苯并咪唑-2-基）苯并咪唑-1-基]甲基] -1H-吲哚- 1-yl]苯甲酸1c可以剂量依赖性方式导致MBP显着降低。口服给药后，其最大反应降低了5 mg / kg的MBP的53 mmHg和10 mg / kg的MBP的64 mmHg，并且显着的降压作用持续了24小时以上，比氯沙坦和替米沙坦都好。旨在确定急性毒性的一项研究表明，1c的急性毒性较低，重量没有明显变化，也没有明显的不良反应。令人鼓舞的结果使1c成为一种有效且持久的抗高血压药物候选者，值得在治疗方面进行进一步研究。

  DOI：

  10.1016/j.ejmech.2016.03.021

文献信息

• Palladium(0)-Catalyzed Dearomative [3 + 2] Cycloaddition of 3-Nitroindoles with Vinylcyclopropanes: An Entry to Stereodefined 2,3-Fused Cyclopentannulated Indoline Derivatives
  作者：Maxime Laugeois、Johanne Ling、Charlène Férard、Véronique Michelet、Virginie Ratovelomanana-Vidal、Maxime R. Vitale

  DOI：10.1021/acs.orglett.7b00784

  日期：2017.5.5

  The palladium(0)-catalyzed diastereoselective dearomative cyclopentannulation of 3-nitroindoles with vinylcyclopropanes is described. This straightforward and highly atom-economical method leads to a wide range of functionalized indolines in good yields and diastereoselectivities and represents an unprecedented entry toward the valuable 2,3-fused cyclopentannulated indoline scaffold.

  描述了钯（0）催化的3-硝基吲哚与乙烯基环丙烷的非对映选择性脱芳香环戊烯环化反应。这种直接且高度原子经济的方法导致了多种官能化的二氢吲哚，具有良好的收率和非对映选择性，代表了有价值的2,3-稠合环戊环二氢吲哚骨架的空前进入。
• Design, synthesis and evaluation of novel potent angiotensin II receptor 1 antagonists
  作者：Xiaolu Bao、Weibo Zhu、Weidong Yuan、Xingbo Zhu、Yijia Yan、Hesheng Tang、Zhilong Chen

  DOI：10.1016/j.ejmech.2016.07.023

  日期：2016.11

  series of new angiotensin II (Ang II) receptor 1 antagonists were designed, synthesized and evaluated. All compounds showed nanomolar affinities for the angiotensin II type 1 receptor in radioligand binding assays and could reduce blood pressure significantly in spontaneously hypertensive rats(SHRs). From which, compound 2b displayed higher affinity binding to angiotensin II type 1 receptor at the same

  设计，合成和评估了一系列新的血管紧张素II（Ang II）受体1拮抗剂。所有化合物在放射性配体结合试验中均显示出与1型血管紧张素II受体的纳摩尔亲和力，并且可以显着降低自发性高血压大鼠（SHRs）的血压。由此可见，化合物2b在放射性配体结合测定中显示出与血管紧张素II 1型受体更高的亲和力结合，与厄贝沙坦的数量级相同，IC50值为1.26 +/- 0.08 nM。2b显示出有效且持久的降血压效果，在SHR中，最大降低反应为15 mg / kg时MBP为40.62 +/- 4.08 mmHg，10 mg / kg时为10 mg / kg 28.39 +/- 2.09 mmHg，39.56 + / -RHR中15 mg / kg时为4.83 mmHg，10 mg / kg时为29.05 +/- 2.20 mmHg，在SHR和RHR中，显着的降压作用持续超过12小时。在单剂量药代动力学实验中，口
• Visible‐Light‐Enabled Multicomponent Cascade Transformation from Indoles to 2‐Azidoindolin‐3‐yl 2‐Aminobenzoates
  作者：Ling‐Ling Zhang、Meng‐Meng Xu、Wen‐Bin Cao、Xiao‐Ping Xu、Shun‐Jun Ji

  DOI：10.1002/adsc.202000637

  日期：2020.8.4

  The synthesis of 2‐azido‐1‐benzoylindolin‐3‐yl 2‐benzamidobenzoate commencing from (1H‐indol‐1‐yl)(phenyl)methanone and trimethylsilyl azide (TMSN3) under oxygen atmosphere is described in this paper. This transformation proceeds via a sequential dearomatization and ring‐opening cascade reaction of indoles in a cascade manner.

  本文描述了在氧气气氛下由（1 H-吲哚-1-基）（苯基）甲酮和三甲基甲硅烷基叠氮化物（TMSN 3）合成2-叠氮基-1-苯甲酰基吲哚-3-基-2-苯甲酰胺基苯甲酸。这种转化通过级联方式依次进行吲哚的脱芳香化和开环级联反应进行。
• Dearomatization of Indoles via Azido Radical Addition and Dioxygen Trapping To Access 2-Azidoindolin-3-ols
  作者：Meng-Meng Xu、Wen-Bin Cao、Rao Ding、Hai-Yan Li、Xiao-Ping Xu、Shun-Jun Ji

  DOI：10.1021/acs.orglett.9b02009

  日期：2019.8.16

  Efficient copper-catalyzed aerobic oxidative dearomatization of indoles with trimethylsilyl azide (TMSN3) for the synthesis of 2-azidoindolin-3-ols has been developed. Molecular oxygen served as the oxygen-atom source in this transformation. The multicomponent reaction is appreciated by its high site- and diastereoselectivity, broad substrate scope, and mild conditions at room temperature.
• Synthesis, Anti-hypertensive Effect of a Novel Angiotensin II AT1 Receptor Antagonist and its Anti-tumor Activity in Prostate Cancer
  作者：Y.-J. Da、W.-D. Yuan、L.-F. Zhu、Z.-L. Chen

  DOI：10.1055/s-0032-1329952

  日期：——

  Since the first non-peptide Ang II receptor antagonist was originally reported, it has become the most common target in the development of new treatments for hypertension. In recent years, all components of the classical RAS have been reported in the prostate, these results suggest the possibility that ARB is a novel therapeutic class of agents for prostate cancer. In this study, a new compound 2-(4-((2-propyl-5-nitro-1H-benzo[d]imidazol-1-yl) methyl)-1H-indol-1-yl) benzoic acid was synthesized and evaluated as a novel angiotensin II AT(1) receptor antagonist by radioligand binding assays, anti-hypertensive assays in vivo and oral acute toxicity test. MTT assays and tests in nude mice were used to demonstrate its anti-tumor activity. This new compound showed high affinity to AT(1) receptor and anti-hypertensive activity in spontaneously hypertensive rats and renal hypertensive rats. Moreover, in human prostate cancer cells and in athymic nude mice bearing human prostate cancer cells, we observed this new compound had an efficient antiproliferative activity in vitro and anti-tumor activity in vivo. The preliminary pharmacological characteristics with oral acute toxicity test suggested that this new compound can be considered as a candidate for both anti-hypertensive and antitumor drug.