N-(3-(cyanomethyl)-1H-indol-5-yl)acetamide

• 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: N-(3-(cyanomethyl)-1H-indol-5-yl)acetamide
• 英文别名: N-[3-(cyanomethyl)-1H-indol-5-yl]acetamide；N-[3-Cyanomethyl-1H-indol-5-yl]acetamide
• 化学式: C₁₂H₁₁N₃O
• 分子量: 213.239
• InChiKey: AQVUPMKJDOYKBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  68.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  异喹啉-5-甲醛 、 N-(3-(cyanomethyl)-1H-indol-5-yl)acetamide 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以7%的产率得到N-(3-((Z)-1-cyano-2-(isoquinolin-5-yl)vinyl)-1H-indol-5-yl)acetamide
  参考文献：
  名称：

  Discovery of the cancer cell selective dual acting anti-cancer agent (Z)-2-(1H-indol-3-yl)-3-(isoquinolin-5-yl)acrylonitrile (A131)

  摘要：

  Selective targeting of cancer cells over normal cells is a key objective of targeted therapy. However few approaches achieve true mechanistic selectivity resulting in debilitating side effects and dose limitation. In this work we describe the discovery of A131 (4a), a new agent with an unprecedented dual mechanism of action targeting both mitosis and autophagy. Compound 4a was first identified in a phenotypic screen in which HeLa cells treated with 4a manifested mitotic arrest along with formation of multiple vesicles. Further investigations showed that 4a causes an increase in mitotic marker pH3 and autophagy marker LC3. Importantly 4a induces cell death in cancer cells while sparing normal cells which regrow after 4a is removed. Dual activities against pH3 and LC3 markers are required for cancer cell selectivity. An extensive SAR investigation confirmed 4a as the optimal dual inhibitor with potency against a panel of 30 cancer cell lines (average antiproliferative GI(50) 1.5 mu M). In a mouse model of paclitaxel-resistant colon cancer, 4a showed 74% tumor growth inhibition when administered at a dose of 20 mg/kg IP twice a day. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.07.011
• 作为产物：
  描述：

  5-amino-1H-indole-3-acetonitrile 、 乙酰氯 在 吡啶 作用下， 以 乙腈 为溶剂， 生成 N-(3-(cyanomethyl)-1H-indol-5-yl)acetamide
  参考文献：
  名称：

  5-substituted 3-aminoalkyl indoles

  摘要：

  揭示了一般式(I)的化合物 ##STR1## 其中R.sub.1代表CHO基团、COR.sub.8基团、CO.sub.2R.sub.8基团、CONR.sub.9R.sub.10基团、CSNR.sub.9R.sub.10基团或SO.sub.2NR.sub.9R.sub.10基团，其中R.sub.8代表烷基、环烷基、芳基或芳基烷基，R.sub.9代表氢原子或烷基基团，R.sub.10代表氢原子或烷基、环烷基、芳基或芳基烷基；R.sub.2、R.sub.3、R.sub.4、R.sub.6和R.sub.7，可能相同也可能不同，每个代表氢原子或C.sub.1-3烷基基团；R.sub.5代表氢原子或烷基、环烷基、烯基或芳基烷基基团或R.sub.4和R.sub.5一起形成芳基烷基亚基团或R.sub.4和R.sub.5与其连接的氮原子一起形成饱和的单环5-至7-成员环；Alk代表含有两个或三个碳原子的烷基链，可以是未取代的或被不超过两个C.sub.1-3烷基基团取代；但是，当R.sub.4和R.sub.5都代表烷基基团时，R.sub.1不代表CHO基团或COR.sub.8基团，当R.sub.4、R.sub.5、R.sub.6和R.sub.7都代表氢原子时，R.sub.1不代表SO.sub.2NH.sub.2基团；以及其生理上可接受的盐、溶剂和生物前体。这些成分被描述为潜在用于治疗偏头痛的，并且可以制备为药物组成物，在常规方法中使用一个或多个药学上可接受的载体或赋形剂。揭示了包括化合物制备的各种过程，例如，将氨基烷基吲哚与一般式R.sub.1OH的酸或相应的酰化剂或与无机氰酸酯或有机异氰酸酯或异硫氰酸酯反应，以在吲哚核上的5位引入所需的R.sub.1基团。

  公开号：

  US04839377A1

文献信息

• [EN] SELECTIVE ANTI-CANCER COMPOUNDS<br/>[FR] COMPOSÉS ANTI-CANCÉREUX SÉLECTIFS
  申请人：NAT UNIV SINGAPORE

  公开号：WO2016200339A1

  公开（公告）日：2016-12-15

  A compound of formula I, wherein the compound of formula I has the structure: wherein R1 to R5, Y, L, Z and X1 to X7 have meanings given in the description, said compounds having utility in the treatment of hyperproliferative disease.

  式I的化合物，其中该化合物具有以下结构：其中R1至R5，Y，L，Z和X1至X7的含义如描述中所示，这些化合物在治疗过度增殖性疾病方面具有用途。
• 3-aminoalkyl-1H-indole-5-urea and amide derivatives
  申请人：McNeilab, Inc.

  公开号：US04803218A1

  公开（公告）日：1989-02-07

  Compounds useful as antihypertensive agents which are 3-aminoalkyl-1H-indole-5-urea or amide derivatives having the following formula: ##STR1## or a pharmaceutically acceptable acid addition salts thereof, wherein: R is C.sub.1-4 loweralkyl, C.sub.1-4 loweralkoxy, phenyl, ##STR2## pyrrolyl, pyridyl or is a substituted nitrogen represented by: ##STR3## wherein R.sub.1 is H or a C.sub.1-4 loweralkyl or phenyl or cycloalkyl; R.sub.2 is H or a C.sub.1-4 loweralkyl; Y is H or halo; R.sub.3 is H or a C.sub.1-4 loweralkyl; R.sub.4 is H or a C.sub.1-4 loweralkyl; R.sub.5 is H or a C.sub.1-4 loweralkyl or carboxymethyl or carboxytrifluoromethyl; R.sub.6 is H or a C.sub.1-4 loweralkyl, and R.sub.5 and R.sub.6 may also be taken together as an N-loweralkyl-pyrrolidinylidene group.

  以下为翻译结果： 该化合物是3-氨基烷基-1H-吲哚-5-脲或酰胺衍生物，可用作降压剂。其化学式如下：##STR1## 或其药学上可接受的酸加成盐，其中：R为C.sub.1-4低烷基，C.sub.1-4低烷氧基，苯基，##STR2## 吡咯基，吡啶基或是一个被代替的氮原子，表示为：##STR3## 其中，R.sub.1为H或C.sub.1-4低烷基、苯基或环烷基；R.sub.2为H或C.sub.1-4低烷基；Y为H或卤素；R.sub.3为H或C.sub.1-4低烷基；R.sub.4为H或C.sub.1-4低烷基；R.sub.5为H或C.sub.1-4低烷基、羧甲基或羧基三氟甲基；R.sub.6为H或C.sub.1-4低烷基，且R.sub.5和R.sub.6也可以组成一个N-低烷基-吡咯烷基亚胺基团。
• Selective anti-cancer compounds
  申请人：NATIONAL UNIVERSITY OF SINGAPORE

  公开号：US10308631B2

  公开（公告）日：2019-06-04

  A compound of formula I, wherein the compound of formula I has the structure: wherein R1 to R5, Y, L, Z and X1 to X7 have meanings given in the description, said compounds having utility in the treatment of hyperproliferative disease.

  一种式 I 的化合物，其中式 I 的化合物具有如下结构： 其中 R1 至 R5、Y、L、Z 和 X1 至 X7 的含义如描述中所给出，所述化合物在治疗过度增殖性疾病中具有实用性。
• (Z)-2-(1H-INDOL-3-YL)-3-(ISOQUINOLIN-5-YL)ACRYLONITRILE DERIVATIVES AND RELATED COMPOUNDS WITH LYSOSOME INHIBITORY AND ANTI-MITOTIC ACTIVITY FOR TREATING HYPERPROLIFERATIVE DISEASES
  申请人：National University of Singapore

  公开号：EP3307724B1

  公开（公告）日：2020-06-10
• SELECTIVE ANTI-CANCER COMPOUNDS
  申请人：NATIONAL UNIVERSITY OF SINGAPORE

  公开号：US20180179178A1

  公开（公告）日：2018-06-28

  A compound of formula I, wherein the compound of formula I has the structure: wherein R 1 to R 5 , Y, L, Z and X 1 to X 7 have meanings given in the description, said compounds having utility in the treatment of hyperproliferative disease.