N-[6-(3-azidopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl]acetamide | 1383663-13-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: N-[6-(3-azidopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl]acetamide
• 英文别名: N-[6-(3-azidopropyl)-5,11-dioxoindeno[1,2-c]isoquinolin-3-yl]acetamide
• CAS: 1383663-13-5
• 化学式: C₂₁H₁₇N₅O₃
• 分子量: 387.398
• InChiKey: VQVWPZPBKLGGKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[6-(3-azidopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl]acetamide 在 sodium tetrahydroborate 、 亚磷酸三乙酯 作用下， 以 甲醇 、 苯 为溶剂， 反应 12.33h， 生成 N-[6-(3-aminopropyl)-11-hydroxy-5-oxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl]acetamide
  参考文献：
  名称：

  Identification, Synthesis, and Biological Evaluation of the Metabolites of 3-Amino-6-(3′-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11-(6H)dione (AM6–36), a Promising Rexinoid Lead Compound for the Development of Cancer Chemotherapeutic and Chemopreventive Agents

  摘要：

  Activation of the retinoid X receptor (RXR), which is involved in cell proliferation, differentiation, and apoptosis, is a strategy for cancer chemotherapy and chemoprevention, and 3-amino-6-(3'-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11-(6H)dione (AM6-36) (3) is among the few RXR ligands known. The presently reported studies of 3 include its binding to human plasma proteins, metabolic stability using human liver microsomes, metabolism by human liver microsomes and hepatocytes, and in vivo disposition in rat serum, liver, and mammary tissue. Compound 3 was 75% bound to human plasma proteins, and its metabolic stability was much greater than propranolol. One phase I metabolite was formed by human liver microsomes, seven phase I and II metabolites were formed by human hepatoc-ytes, and five metabolites were detected in rat serum and liver after oral administration. The putative metabolites predicted using LC-MS-MS were synthesized to confirm their structures and to provide sufficient material for investigation of induction of RXRE transcriptional activity and inhibition of NF kappa B.

  DOI：

  10.1021/jm3006806
• 作为产物：
  描述：

  3-amino-6-(3-chloropropyl)-5,6-dihydro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline 在 sodium azide 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 8.0h， 生成 N-[6-(3-azidopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl]acetamide
  参考文献：
  名称：

  Identification, Synthesis, and Biological Evaluation of the Metabolites of 3-Amino-6-(3′-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11-(6H)dione (AM6–36), a Promising Rexinoid Lead Compound for the Development of Cancer Chemotherapeutic and Chemopreventive Agents

  摘要：

  Activation of the retinoid X receptor (RXR), which is involved in cell proliferation, differentiation, and apoptosis, is a strategy for cancer chemotherapy and chemoprevention, and 3-amino-6-(3'-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11-(6H)dione (AM6-36) (3) is among the few RXR ligands known. The presently reported studies of 3 include its binding to human plasma proteins, metabolic stability using human liver microsomes, metabolism by human liver microsomes and hepatocytes, and in vivo disposition in rat serum, liver, and mammary tissue. Compound 3 was 75% bound to human plasma proteins, and its metabolic stability was much greater than propranolol. One phase I metabolite was formed by human liver microsomes, seven phase I and II metabolites were formed by human hepatoc-ytes, and five metabolites were detected in rat serum and liver after oral administration. The putative metabolites predicted using LC-MS-MS were synthesized to confirm their structures and to provide sufficient material for investigation of induction of RXRE transcriptional activity and inhibition of NF kappa B.

  DOI：

  10.1021/jm3006806

文献信息

• SYNTHESIS AND USE OF DUAL TYROSYL-DNA PHOSPHODIESTERASE I (Tdp1) - TOPOISOMERASE I (Top1) INHIBITORS
  申请人：Purdue Research Foundation

  公开号：US20150133445A1

  公开（公告）日：2015-05-14

  The invention described herein pertains to the synthesis and use of certain N-substituted indenoisoquinoline compounds which inhibit the activity Tyrosyl-DNA Phosphodiesterase I (Tdp1) or Topoisomerase I (Top1) or both, or otherwise demonstrate anticancer activity. Also disclosed are novel N-substituted indenoisoquinoline compounds and pharmaceutical compositions comprising the novel N-substituted indenoisoquinoline compounds.

  本发明涉及合成和使用某些N-取代吲哚异喹啉化合物，其抑制酪氨酸-DNA磷酸二酯酶I（Tdp1）或拓扑异构酶I（Top1）或两者的活性，或表现出抗癌活性。还公开了新型N-取代吲哚异喹啉化合物和包含新型N-取代吲哚异喹啉化合物的制药组合物。
• US8912213B2
  申请人：——

  公开号：US8912213B2

  公开（公告）日：2014-12-16
• US9175002B2
  申请人：——

  公开号：US9175002B2

  公开（公告）日：2015-11-03
• US9402842B2
  申请人：——

  公开号：US9402842B2

  公开（公告）日：2016-08-02
• Identification, Synthesis, and Biological Evaluation of the Metabolites of 3-Amino-6-(3′-aminopropyl)-5<i>H</i>-indeno[1,2-<i>c</i>]isoquinoline-5,11-(6<i>H</i>)dione (AM6–36), a Promising Rexinoid Lead Compound for the Development of Cancer Chemotherapeutic and Chemopreventive Agents
  作者：Lian Chen、Martin Conda-Sheridan、P. V. Narasimha Reddy、Andrew Morrell、Eun-Jung Park、Tamara P. Kondratyuk、John M. Pezzuto、Richard B. van Breemen、Mark Cushman

  DOI：10.1021/jm3006806

  日期：2012.6.28

  Activation of the retinoid X receptor (RXR), which is involved in cell proliferation, differentiation, and apoptosis, is a strategy for cancer chemotherapy and chemoprevention, and 3-amino-6-(3'-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11-(6H)dione (AM6-36) (3) is among the few RXR ligands known. The presently reported studies of 3 include its binding to human plasma proteins, metabolic stability using human liver microsomes, metabolism by human liver microsomes and hepatocytes, and in vivo disposition in rat serum, liver, and mammary tissue. Compound 3 was 75% bound to human plasma proteins, and its metabolic stability was much greater than propranolol. One phase I metabolite was formed by human liver microsomes, seven phase I and II metabolites were formed by human hepatoc-ytes, and five metabolites were detected in rat serum and liver after oral administration. The putative metabolites predicted using LC-MS-MS were synthesized to confirm their structures and to provide sufficient material for investigation of induction of RXRE transcriptional activity and inhibition of NF kappa B.