3-(3-Formyl-indol-1-ylmethyl)-benzonitrile | 928708-60-5

• 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: 3-(3-Formyl-indol-1-ylmethyl)-benzonitrile
• 英文别名: 3-((3-Formyl-1H-indol-1-yl)methyl)benzonitrile；3-[(3-formylindol-1-yl)methyl]benzonitrile
• CAS: 928708-60-5
• 化学式: C₁₇H₁₂N₂O
• 分子量: 260.295
• InChiKey: LMJSQYFVDVKPGV-UHFFFAOYSA-N

物化性质

• 沸点：
  502.8±35.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  45.8
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  3-(3-Formyl-indol-1-ylmethyl)-benzonitrile 在 氢气 作用下， 生成 1-(3-cyanobenzyl)-3-(2-β-naphthylethyl)indole
  参考文献：
  名称：

  Design and Structure−Activity Relationships of Potent and Selective Inhibitors of Blood Coagulation Factor Xa

  摘要：

  The discovery of a series of non-peptide factor Xa (FXa) inhibitors incorporating 3-(S)-amino-2-pyrrolidinone as a central template is described. After identifying compound 4, improvements in in vitro potency involved modifications of the liphophilic group and optimizing the angle of presentation of the amidine group to the S1 pocket of FXa. These studies ultimately led to compound RPR120844, a potent inhibitor of FXa (Ki = 7 nM) which shows selectivity for FXa over trypsin, thrombin, and several fibrinolytic serine proteinases. RPR120844 is an effective anticoagulant in both the rat model of FeCl2-induced carotid artery thrombosis and the rabbit model of jugular vein thrombus formation.

  DOI：

  10.1021/jm990040h
• 作为产物：
  描述：

  3-吲哚甲醛 、 alkaline earth salt of/the/ methylsulfuric acid 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 0.08h， 生成 3-(3-Formyl-indol-1-ylmethyl)-benzonitrile
  参考文献：
  名称：

  新型取代的吲哚-3-羧基甲醛的噻二唑酰肼的合成及其抗分枝杆菌活性

  摘要：

  制备了一系列新的取代吲哚的硫代碳氢azo及其相应的噻二唑衍生物，并通过不同的分析和光谱方法证实了它们的结构。通过顺序合成策略制备衍生物，包括在吲哚环的N -1位被各种脂族和苄基取代基取代，然后与硫代碳酰肼缩合，最后由原甲酸三乙酯环化。测试了这些衍生物对牛分枝杆菌BCG的抗分枝杆菌活性，结果表明，在合成的化合物中，噻二唑衍生物4e，4f，4n，4p，4q和4t表现出最高的活性，IC 50值为3.91μg/ mL。结果表明，噻二唑部分在发挥抗分枝杆菌活性中起着至关重要的作用。

  DOI：

  10.1111/cbdd.12230

文献信息

• Synthesis, antimycobacterial and anticancer activity of novel indole-based thiosemicarbazones
  作者：Vida Mashayekhi、Kamaleddin Haj Mohammad Ebrahim Tehrani、Parisa Azerang、Soroush Sardari、Farzad Kobarfard

  DOI：10.1007/s12272-013-0242-z

  日期：2021.8

  Based on the structural elements of bioactive indole-based compounds, a series of novel 1-substituted indole-3-carboxaldehyde thiosemicarbazones were synthesized as potential antimycobacterial and anticancer agents. The derivatives were prepared via a two-step methodology including N-alkylation(benzylation) of indole-3-carboxaldehyde and conversion of the intermediate aldehydes to corresponding thiosemicarbazones. The derivatives were evaluated for their antimycobacterial activity and compounds 3d (R = propyl) and 3q (R = 4-nitrobenzyl) were among the most potent and selective derivatives with IC50 values of 0.9 and 1.9 μg/mL respectively. The anticancer activity of the derivatives was also assessed against a panel of tumor cell lines. Compounds 3t, 3u, 3v and 3w efficiently inhibited the majority of the cancer cell lines with considerable selectivity.

  基于生物活性吲哚类化合物的结构元素，合成了一系列新型1-取代吲哚-3-甲酰基缩氨基硫脲作为潜在的抗分枝杆菌和抗癌剂。这些衍生物通过两步法合成：包括吲哚-3-甲酰基的N-烷基化（苄基化）以及中间体醛转化为相应的缩氨基硫脲。评估了这些衍生物的抗分枝杆菌活性，其中化合物3d（R = 丙基）和3q（R = 4-硝基苄基）是活性最强且选择性最高的衍生物，其IC50值分别为0.9和1.9 μg/mL。还评估了这些衍生物对一组肿瘤细胞系的抗癌活性。化合物3t、3u、3v和3w能有效抑制大多数癌细胞系，并具有相当的选择性。
• Design, Synthesis and Anticancer Activity of 4-Morpholinothieno[3,2-<i>d</i>]pyrimidine Derivatives Bearing Arylmethylene Hydrazine Moiety
  作者：Wufu Zhu、Xin Zhai、Qiangqiang Fu、Fei Guo、Mei Bai、Jianqiang Wang、Haiyan Wang、Ping Gong

  DOI：10.1248/cpb.c12-00342

  日期：——

  Three series of 4-morpholinothieno[3,2-d]pyrimidine derivatives containing arylmethylene hydrazine moiety (11a–f, 13a–k and 15a–h) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. The synthesized compounds were evaluated for their cytotoxicity against three cancer cell lines (H460, HT-29, MDA-MB-231). Most of them exhibited moderate to significant cytotoxicity and high-selectivity against one or more cell lines, especially compounds 11c, 13b, 15f and 15g possessing dramatically increased cytotoxicity as compared with the positive controls, which were further evaluated for six other cancer cell lines and one normal cell line. The most promising compound 11c, bearing 3,4-methylenedioxy phenyl group, showed remarkable cytotoxicity against H460, HT-29 and MDA-MB-231 cell lines with IC50 values of 0.003 µM, 0.42 µM and 0.74 µM, which was 1.6- to 290-fold more potent than GDC-0941.

  合成了三系列含有芳基亚甲基肼部分的4-吗啉硫烯并[3,2-d]嘧啶衍生物（11a–f, 13a–k 和 15a–h），并确认了它们的化学结构以及相对立体化学。合成的化合物对三种癌细胞系（H460, HT-29, MDA-MB-231）的细胞毒性进行了评估。大多数化合物表现出中等到显著的细胞毒性，并对一种或多种细胞系展现出高选择性，特别是化合物11c、13b、15f和15g与阳性对照相比显示出显著提高的细胞毒性，后者进一步在另外六种癌细胞系和一种正常细胞系中进行了评估。最有前景的化合物11c，含有3,4-亚甲基二氧苯基基团，对H460、HT-29和MDA-MB-231细胞系显示出显著细胞毒性，IC50值分别为0.003 µM、0.42 µM和0.74 µM，比GDC-0941的效力提高了1.6到290倍。
• Synthesis and Biological Evaluation of Novel 6-Hydrazinyl-2,4-bismorpholino pyrimidine and 1,3,5-Triazine Derivatives as Potential Antitumor Agents
  作者：Wufu Zhu、Yajing Liu、Yanfang Zhao、Haiyan Wang、Li Tan、Weijie Fan、Ping Gong

  DOI：10.1002/ardp.201200074

  日期：2012.10

  6‐hydrazinyl‐2,4‐bismorpholino pyrimidine and 1,3,5‐triazine derivatives (5a–5l and 8a–8o) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. All the synthesized compounds were evaluated for antiproliferative activity against three cancer cell lines (H460, HT‐29, and MDA‐MB‐231). Several potent compounds were further evaluated against two other cell lines

  合成了一系列 6-肼基-2,4-双吗啉代嘧啶和 1,3,5-三嗪衍生物（5a-5l 和 8a-8o），并确认了它们的化学结构和相对立体化学。评估了所有合成化合物对三种癌细胞系（H460、HT-29 和 MDA-MB-231）的抗增殖活性。针对其他两种细胞系 (U87MG, H1975) 进一步评估了几种有效化合物。大多数制备的化合物，特别是 IC50 值（分别为 0.07 和 0.05 µM）在 nM 范围内的化合物 5c 和 5j，与化合物 1 相比，表现出中等到优异的抗增殖活性和对 H460 癌细胞系的高选择性。有前途的化合物 5j，在苯环的 3 位具有氰基，
• Design, synthesis and 3D-QSAR analysis of novel 2-hydrazinyl-4-morpholinothieno[3,2-d]pyrimidine derivatives as potential antitumor agents
  作者：Wufu Zhu、Yajing Liu、Xin Zhai、Xiao Wang、Yan Zhu、Di Wu、Hongyu Zhou、Ping Gong、Yanfang Zhao

  DOI：10.1016/j.ejmech.2012.09.002

  日期：2012.11

  A series of 2-hydrazinyl-4-morpholinothieno[3,2-d]pyrimidine derivatives were synthesized and evaluated for their cytotoxic activities against five cancer cell lines. Most of them exhibited moderate to significant cytotoxic activities and high-selectivity against one or more cell lines, and nearly all of them had higher potency than positive controls against MDA-MB-231 cell line. The most promising compound 15f showed strong cytotoxic activities against H460, HT-29 and MDA-MB-231 cell lines, which were 1.7- to 66.5-folds more active than 2-(1H-Indazol-4-yl)-6-((4-(methylsulfonyl)-1-piperazinyl)methyl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidine(GDC-0941). To investigate the SARs of thieno[3,2-d]pyrimidine derivatives in more details, CoMFA (q(2) = 0.436, r(2) = 0.937) and CoMSIA (q(2) = 0.706, r(2) = 0.947) models on H460 cell line were established. The generated 3D-QSAR models can be used for further rational design of novel thienopyrimidines as highly potent and selective cytotoxic agents. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Design and Structure−Activity Relationships of Potent and Selective Inhibitors of Blood Coagulation Factor Xa
  作者：William R. Ewing、Michael R. Becker、Vincent E. Manetta、Roderick S. Davis、Henry W. Pauls、Helen Mason、Yong Mi Choi-Sledeski、Daniel Green、Don Cha、Alfred P. Spada、Daniel L. Cheney、Jonathan S. Mason、Sebastien Maignan、Jean-Pierre Guilloteau、Karen Brown、Dennis Colussi、Ross Bentley、Jeff Bostwick、Charles J. Kasiewski、Suzanne R. Morgan、Robert J. Leadley、Christopher T. Dunwiddie、Mark H. Perrone、Valeria Chu

  DOI：10.1021/jm990040h

  日期：1999.9.1

  The discovery of a series of non-peptide factor Xa (FXa) inhibitors incorporating 3-(S)-amino-2-pyrrolidinone as a central template is described. After identifying compound 4, improvements in in vitro potency involved modifications of the liphophilic group and optimizing the angle of presentation of the amidine group to the S1 pocket of FXa. These studies ultimately led to compound RPR120844, a potent inhibitor of FXa (Ki = 7 nM) which shows selectivity for FXa over trypsin, thrombin, and several fibrinolytic serine proteinases. RPR120844 is an effective anticoagulant in both the rat model of FeCl2-induced carotid artery thrombosis and the rabbit model of jugular vein thrombus formation.