N-(3-formyl-1H-indol-5-yl)acetamide | 91137-92-7

• 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: N-(3-formyl-1H-indol-5-yl)acetamide
• CAS: 91137-92-7
• 化学式: C₁₁H₁₀N₂O₂
• 分子量: 202.213
• InChiKey: IZHSPYMLKHVVBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  62
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(3-formyl-1H-indol-5-yl)acetamide 在 sodium tetrahydroborate 、 sodium methylate 作用下， 以 甲醇 、 formamide 为溶剂， 反应 32.25h， 生成 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-乙酰氨基吲哚 、 N,N-二甲基甲酰胺 在 三氯氧磷 作用下， 反应 1.83h， 以52%的产率得到N-(3-formyl-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

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。
• 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.
• Discovery of the cancer cell selective dual acting anti-cancer agent (Z)-2-(1H-indol-3-yl)-3-(isoquinolin-5-yl)acrylonitrile (A131)
  作者：Cheng Shang See、Mayumi Kitagawa、Pei-Ju Liao、Kyung Hee Lee、Jasmine Wong、Sang Hyun Lee、Brian W. Dymock

  DOI：10.1016/j.ejmech.2018.07.011

  日期：2018.8

  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.