2-(4-hydroxyphenyl)-9-(2-methoxyphenyl)-8-oxo-8,9-dihydro-7H-purine-6-carboxamide | 1022155-05-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-hydroxyphenyl)-9-(2-methoxyphenyl)-8-oxo-8,9-dihydro-7H-purine-6-carboxamide
• 英文别名: 2-(4-hydroxyphenyl)-9-(2-methoxyphenyl)-8-oxopurine-6-carboxamide；2-(4-hydroxyphenyl)-9-(2-methoxyphenyl)-8-oxo-7H-purine-6-carboxamide
• CAS: 1022155-05-0
• 化学式: C₁₉H₁₅N₅O₄
• 分子量: 377.359
• InChiKey: XIHROTCGKRDGKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  131
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-甲氧基苯基异氰酸酯 在 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 48.0h， 生成 2-(4-hydroxyphenyl)-9-(2-methoxyphenyl)-8-oxo-8,9-dihydro-7H-purine-6-carboxamide
  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

文献信息

• Structure-guided development of purine amide, hydroxamate, and amidoxime for the inhibition of non-small cell lung cancer
  作者：Meng-Ruo Huang、Yuan-Ling Hsu、Tzu-Chen Lin、Ting-Jen Cheng、Ling-Wei Li、Yu-Wei Tseng、Yu-shu Chou、Jyung-Hurng Liu、Szu-Hua Pan、Jim-Min Fang、Chi-Huey Wong

  DOI：10.1016/j.ejmech.2019.07.054

  日期：2019.11

  structure-activity relationship as a basis for the construction of an advanced pharmacophore model. This model suggests that purine-6-hydroxamate and purine-6-amidoxime analogs could form more hydrogen bonds with a target protein to enhance the inhibitory activities against H1975 cells. Among the series of analogs, hydroxamate 17 and amidoxime 19a exhibited excellent potency against H1975 cells (IC50 < 1.5 μM)

  先前已确定8-氧嘌呤-6-羧酰胺化合物（1a）是非小细胞肺癌（NSCLC）的抑制剂。在这项研究中，合成了30多个在C2，N7，C8和N9位置具有变化的嘌呤-6-羧酰胺衍生物，以研究其结构活性关系，以此为基础构建高级药效团模型。该模型表明嘌呤6-异羟肟酸酯和嘌呤6-d肟类似物可与靶蛋白形成更多的氢键，从而增强对H1975细胞的抑制活性。在一系列类似物中，异羟肟酸酯17和a胺肟19a对H1975细胞（IC50 <1.5μM）和其他具有野生型或突变表皮生长因子受体（EGFR）的肺癌细胞表现出出色的效力。小鼠实验表明，化合物17和19a是有效的抗癌药，没有明显的毒性。确定了诱导细胞凋亡的作用机制，涉及微管片段化和p53介导的信号通路。
• [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。
• Treatment of cancer with TOR kinase inhibitors
  申请人：Signal Pharmaceuticals, LLC

  公开号：US11166950B2

  公开（公告）日：2021-11-09

  Provided herein are methods for treating or preventing a solid tumor, non-Hodgkin lymphoma or multiple myeloma in a patient, comprising administering an effective amount of a TOR kinase inhibitor to a patient having a solid tumor, non-Hodgkin lymphoma or multiple myeloma.

  本文提供了治疗或预防患者实体瘤、非霍奇金淋巴瘤或多发性骨髓瘤的方法，包括向患有实体瘤、非霍奇金淋巴瘤或多发性骨髓瘤的患者施用有效量的TOR激酶抑制剂。
• WO2008/51494
  申请人：——

  公开号：——

  公开（公告）日：——