1-(cyclopropylmethyl)-5-amino-1H-indole | 289037-49-6

• 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: 1-(cyclopropylmethyl)-5-amino-1H-indole
• 英文别名: 1-(Cyclopropylmethyl)-1H-indol-5-amine；1-(cyclopropylmethyl)indol-5-amine
• CAS: 289037-49-6
• 化学式: C₁₂H₁₄N₂
• 分子量: 186.257
• InChiKey: AYIPLNZQXCQVAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  31
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(cyclopropylmethyl)-5-amino-1H-indole 在 calcium sulfate 、 溶剂黄146 作用下， 以 二苯醚 、 乙醇 为溶剂， 生成 3-(cyclopropylmethyl)-7-(3,4-dimethoxyphenyl)-3H-pyrrolo[3,2-f]quinolin-9(6H)-one
  参考文献：
  名称：

  Novel 3-Substituted 7-Phenylpyrrolo[3,2-f]quinolin-9(6H)-ones as Single Entities with Multitarget Antiproliferative Activity

  摘要：

  A series of chemically modified 7-phenylpyrrolo[3,2-f]quinolinones was synthesized and evaluated as anticancer agents. Among them, the most cytotoxic (subnanomolar GI(50) values) amidic derivative 5f was shown to act as an inhibitor of tubulin polymerization (IC50, 0.99 mu M) by binding to the colchicine site with high affinity. Moreover, 5f induced cell cycle arrest in the G2/M phase of the cell cycle in a concentration dependent manner, followed by caspase-dependent apoptotic cell death. Compound 5f also showed lower toxicity in nontumoral cells, suggesting selectivity toward cancer cells. Additional experiments revealed that 5f inhibited the enzymatic activity of multiple kinases, including AURKA, FLT3, GSK3A, MAP3K, MEK, RSK2, RSK4, PLK4, ULK1, and JAK1. Computational studies showed that 5f can be properly accommodated in the colchicine binding site of tubulin as well as in the ATP binding clefts of all examined kinases. Our data indicate that the excellent antiproliferative profile of 5f may be derived from its interactions with multiple cellular targets.

  DOI：

  10.1021/acs.jmedchem.5b00805
• 作为产物：
  描述：

  5-硝基吲哚 在 palladium 10% on activated carbon 、 氢气 、 sodium hydride 作用下， 以 甲苯 为溶剂， 生成 1-(cyclopropylmethyl)-5-amino-1H-indole
  参考文献：
  名称：

  某些3-苯基-吡咯并喹唑啉酮类化合物对血小板聚集的抑制活性及其合成与评价

  摘要：

  从5-氨基吲哚开始，经与N-缩合反应，合成了一系列3-苯基-2,7-二氢-1H-吡咯并[3,2 - f ]喹唑啉-1-酮衍生物（3-PPyQZ）。乙氧基羰基硫代苯甲酰胺，然后进行热环化。基于其与报道的抗凝血酶吡咯并喹唑啉的结构相似性，首先测试了这些衍生物抑制血小板聚集的能力。它们中的一些在微摩尔范围内对胶原蛋白和凝血酶诱导的聚集具有体外抑制作用，并且比某些苯基-吡咯并喹啉酮所显示的抑制作用高得多。实验以确定最有效抑制剂的作用机理（化合物18）表明它在至少两个位点起作用：一个在激动剂诱导的胞质[Ca 2+ ]增加之前，一个在血小板激活级联的这一步骤之后。该化合物还抑制凝血酶诱发的蛋白Tyr-磷酸化。尽管得出明确的结论为时过早，但目前的结果表明，3-PPyQZ结构与血小板聚集化合物18的强效抑制剂可能构成合成潜在抗血栓形成剂的起点。

  DOI：

  10.1016/j.ejmech.2011.12.026

文献信息

• Synthesis and in vitro Evaluation of 3H-Pyrrolo[3,2-f]quinolin-9-one Derivatives That Show Potent and Selective Anti-leukemic Activity
  作者：Maria Grazia Ferlin、Roberta Bortolozzi、Paola Brun、Ignazio Castagliuolo、Ernest Hamel、Giuseppe Basso、Giampietro Viola

  DOI：10.1002/cmdc.201000180

  日期：——

  2‐f]quinolin‐9‐ones were synthesized and evaluated for their antiproliferative activity. The most active derivatives showed high selectivity against human leukemia cell lines and potently inhibited their growth, with GI50 values in the nanomolar range. The active compounds strongly blocked tubulin assembly and colchicine binding to tubulin. Their activities were equal to or greater than that of the

  一系列新的取代的7-苯基-3- ħ吡咯并[3,2- ˚F ]喹啉-9-酮的合成和评价它们的抗增殖活性。最活跃的衍生物对人类白血病细胞系显示出高选择性并有效抑制它们的生长，GI 50值在纳摩尔范围内。活性化合物强烈阻断微管蛋白组装和秋水仙碱与微管蛋白的结合。它们的活性等于或大于参考化合物考布他汀 A-4 的活性。流式细胞术研究表明，两种最活跃的化合物在 G 2/M 细胞周期阶段以浓度依赖性方式。这种效应与细胞凋亡、线粒体去极化、活性氧的产生、caspase-3 的激活和聚（ADP-核糖）聚合酶的裂解有关。
• Synthesis and evaluation of platelet aggregation inhibitory activity of some 3-phenyl-pyrroloquinazolinones
  作者：Maria Grazia Ferlin、Christian Borgo、Renzo Deana

  DOI：10.1016/j.ejmech.2011.12.026

  日期：2012.2

  derivatives were first tested for their capacity to inhibit platelet aggregation. Some of them had in vitro inhibitory effects on collagen and thrombin-induced aggregation in the micromolar range, and much higher inhibition than that shown by some phenyl-pyrroloquinolinones. Experiments to determine the mechanism of action of the most potent inhibitor (compound 18) indicated that it acts in at least two

  从5-氨基吲哚开始，经与N-缩合反应，合成了一系列3-苯基-2,7-二氢-1H-吡咯并[3,2 - f ]喹唑啉-1-酮衍生物（3-PPyQZ）。乙氧基羰基硫代苯甲酰胺，然后进行热环化。基于其与报道的抗凝血酶吡咯并喹唑啉的结构相似性，首先测试了这些衍生物抑制血小板聚集的能力。它们中的一些在微摩尔范围内对胶原蛋白和凝血酶诱导的聚集具有体外抑制作用，并且比某些苯基-吡咯并喹啉酮所显示的抑制作用高得多。实验以确定最有效抑制剂的作用机理（化合物18）表明它在至少两个位点起作用：一个在激动剂诱导的胞质[Ca 2+ ]增加之前，一个在血小板激活级联的这一步骤之后。该化合物还抑制凝血酶诱发的蛋白Tyr-磷酸化。尽管得出明确的结论为时过早，但目前的结果表明，3-PPyQZ结构与血小板聚集化合物18的强效抑制剂可能构成合成潜在抗血栓形成剂的起点。
• 3-Substituted 7-Phenyl-Pyrroloquinolinones Show Potent Cytotoxic Activity in Human Cancer Cell Lines
  作者：Venusia Gasparotto、Ignazio Castagliuolo、Maria Grazia Ferlin

  DOI：10.1021/jm070534b

  日期：2007.11.1

  A novel series of 3-alkyl-substituted 7-phenyl-3H-pyrrolo[3,2-jlquinolin-9-ones (7-PPyQs) was synthesized with the aim to optimize the cytotoxic activity of recently identified PPyQs, promising inhibitors of tubulin polymerization. All compounds inhibited the growth of 11 human tumor cell lines at submicromolar concentrations as well as two human resistant cancer sublines, A549-T12 and A549-T24. FACS analysis indicated that all compounds caused significant arrest of the A549 cell cycle in G(2)/M phase at 0.1 and 1 mu M and a good correlation between the cytotoxicity IC50 and their ability to block the cell cycle was observed.
• Heteroaromatic bicyclic derivatives useful as anticancer agents
  申请人：Pfizer Products Inc.

  公开号：EP1029853B1

  公开（公告）日：2004-02-25
• US6465449B1
  申请人：——

  公开号：US6465449B1

  公开（公告）日：2002-10-15