2-(4-ethoxyphenyl)-9-(3-carboxy)phenyl-8-oxopurine-6-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2-(4-ethoxyphenyl)-9-(3-carboxy)phenyl-8-oxopurine-6-carboxamide
• 英文别名: 3-[6-carbamoyl-2-(4-ethoxyphenyl)-8-oxo-7H-purin-9-yl]benzoic acid
• 化学式: C₂₁H₁₇N₅O₅
• 分子量: 419.396
• InChiKey: YMVQTSOIIKPZDE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  148
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(4-ethoxyphenyl)-9-(3-carboxy)phenyl-8-oxopurine-6-carboxamide 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成
  参考文献：
  名称：

  Purine-Type Compounds Induce Microtubule Fragmentation and Lung Cancer Cell Death through Interaction with Katanin

  摘要：

  Microtubule targeting agents (MTAs) constitute a class of drugs for cancer treatment. Despite many MTAs have been proven to significantly improve the treatment: outcomes of various malignancies, resistance has usually occurred. By selection from a two million entry chemical library based, on the efficacy and safety, we identified purine-type compounds that were active against lung small cell lung cancer (NSCLC). The purine compound 5a (GRC0321) was an MTA with good effects against NSCLC. Lung cancer cells H1975 treated with 5a could induce microtubule fragmentation, leading to G2/M cell cycle arrest and intrinsic apoptosis. Compound 5a directly targeted katanin and regulated the severing activity of katanin, which cut the cellular microtubules into short pieces and activated c-Jun N-terminal kinases (JNK). The microtubule fragmenting effect of 5a is a unique mechanism in MTAs. It might overcome the resistance problems that most of the MTAs have faced.

  DOI：

  10.1021/acs.jmedchem.6b00797
• 作为产物：
  描述：

  2-(4-ethoxyphenyl)-9-(3-methoxycarbonyl)phenyl-8-oxopurine-6-carboxamide 在 吡啶 、 水 、 sodium hydroxide 作用下， 反应 22.0h， 以78%的产率得到2-(4-ethoxyphenyl)-9-(3-carboxy)phenyl-8-oxopurine-6-carboxamide
  参考文献：
  名称：

  [EN] PURINE COMPOUNDS POSSESSING ANTICANCER ACTIVITY
  [FR] COMPOSÉS PURINE PRÉSENTANT UNE ACTIVITÉ ANTICANCÉREUSE

  摘要：

  本公开提供了式(I')和(I)的化合物，以及其药学上可接受的盐。本文描述的化合物可能在治疗和/或预防增殖性疾病（例如癌症）方面有用。本公开还提供了用于治疗增殖性疾病的药物组合物、试剂盒以及它们的用途。

  公开号：

  WO2017136689A1

文献信息

• [EN] PURINE COMPOUNDS POSSESSING ANTICANCER ACTIVITY<br/>[FR] COMPOSÉS PURINE PRÉSENTANT UNE ACTIVITÉ ANTICANCÉREUSE
  申请人：ACADEMIA SINICA

  公开号：WO2017136689A1

  公开（公告）日：2017-08-10

  The present disclosure provides compounds of Formulas (I') and (I), and pharmaceutically acceptable salts thereof. The compounds described herein may be useful in treating and/or preventing proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions, kits, and uses thereof for treating proliferative diseases.

  本公开提供了式(I')和(I)的化合物，以及其药学上可接受的盐。本文描述的化合物可能在治疗和/或预防增殖性疾病（例如癌症）方面有用。本公开还提供了用于治疗增殖性疾病的药物组合物、试剂盒以及它们的用途。
• Purine compounds possessing anticancer activity
  申请人：Academia Sinica

  公开号：US10765681B2

  公开（公告）日：2020-09-08

  The present disclosure provides compounds of Formulas (I′) and (I), and pharmaceutically acceptable salts thereof. The compounds described herein may be useful in treating and/or preventing proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions, kits, and uses thereof for treating proliferative diseases.

  本公开提供了式(I′)和(I)化合物及其药学上可接受的盐类。本文所述化合物可用于治疗和/或预防增殖性疾病（如癌症）。本公开还提供了用于治疗增殖性疾病的药物组合物、试剂盒及其用途。
• Purine-Type Compounds Induce Microtubule Fragmentation and Lung Cancer Cell Death through Interaction with Katanin
  作者：Ting-Chun Kuo、Ling-Wei Li、Szu-Hua Pan、Jim-Min Fang、Jyung-Hurng Liu、Ting-Jen Cheng、Chia-Jen Wang、Pei-Fang Hung、Hsuan-Yu Chen、Tse-Ming Hong、Yuan-Ling Hsu、Chi-Huey Wong、Pan-Chyr Yang

  DOI：10.1021/acs.jmedchem.6b00797

  日期：2016.9.22

  Microtubule targeting agents (MTAs) constitute a class of drugs for cancer treatment. Despite many MTAs have been proven to significantly improve the treatment: outcomes of various malignancies, resistance has usually occurred. By selection from a two million entry chemical library based, on the efficacy and safety, we identified purine-type compounds that were active against lung small cell lung cancer (NSCLC). The purine compound 5a (GRC0321) was an MTA with good effects against NSCLC. Lung cancer cells H1975 treated with 5a could induce microtubule fragmentation, leading to G2/M cell cycle arrest and intrinsic apoptosis. Compound 5a directly targeted katanin and regulated the severing activity of katanin, which cut the cellular microtubules into short pieces and activated c-Jun N-terminal kinases (JNK). The microtubule fragmenting effect of 5a is a unique mechanism in MTAs. It might overcome the resistance problems that most of the MTAs have faced.