6-Methoxy-7-benzyloxy-2,4-(1H,3H)-chinazolindion | 60548-00-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-Methoxy-7-benzyloxy-2,4-(1H,3H)-chinazolindion
• 英文别名: 7-(benzyloxy)-6-methoxyquinazoline-2,4(1H,3H)-dione；7-benzyloxy-6-methoxy-1H-quinazoline-2,4-dione；6-methoxy-7-phenylmethoxy-1H-quinazoline-2,4-dione
• CAS: 60548-00-7
• 化学式: C₁₆H₁₄N₂O₄
• 分子量: 298.298
• InChiKey: YXHRCWBYZRCCFE-UHFFFAOYSA-N

物化性质

• 密度：
  1.296±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-Methoxy-7-benzyloxy-2,4-(1H,3H)-chinazolindion 在 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 6.0h， 以97%的产率得到2,4-二氯-6-甲氧基-7-苯基甲氧基喹唑啉
  参考文献：
  名称：

  Histone lysine methyltransferase structure activity relationships that allow for segregation of G9a inhibition and anti-Plasmodium activity

  摘要：

  我们确定了关键的 SAR 特征，表明对于喹唑啉抑制剂化学类型，可以实现高寄生虫与 G9a 的选择性。

  DOI：

  10.1039/c7md00052a
• 作为产物：
  描述：

  4-羟基-3-甲氧基苯甲腈 在 硝酸 、 铁粉 、 potassium carbonate 、 氯化铵 、 溶剂黄146 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 46.0h， 生成 6-Methoxy-7-benzyloxy-2,4-(1H,3H)-chinazolindion
  参考文献：
  名称：

  [EN] BLOCKING TOLL-LIKE RECEPTOR 9 SIGNALING WITH SMALL MOLECULE ANTAGONIST
  [FR] BLOCAGE DE LA SIGNALISATION PAR LE TLR9 (TOLL-LIKE RECEPTOR 9) AVEC UN ANTAGONISTE À PETITES MOLÉCULES

  摘要：

  公开号：

  WO2017163264A4

文献信息

• Blocking toll-like receptor 9 signaling with small molecule antagonist
  申请人：Council of Scientific & Industrial Research

  公开号：US10662177B2

  公开（公告）日：2020-05-26

  The present invention relates to small molecule 4-(piperazin-1-yl)quinazolin-2-amino compounds with formula (I) useful for inhibiting signalling by certain toll-like receptors (TLRs), especially TLR9. Toll-like receptors (TLRs) are members of the larger family of evolutionarily conserved pattern recognition receptors which are critical first line of defense for self-nonself discrimination by the host immune response. Aberrant TLR9 activation is implicated in autoreactive inflammation in different autoimmune diseases. The invention depicts compounds with formula (I), composition and methods can be used in a number of clinical applications, including as pharmaceutical agents and methods for treating conditions involving unwanted immune activity due to TLR9 activation.

  本发明涉及小分子 4-(哌嗪-1-基)喹唑啉-2-氨基化合物，其式(I)有助于抑制某些类毒素受体（TLRs），特别是 TLR9 的信号传导。类毒素受体（TLRs）是进化保守的模式识别受体大家族的成员，是宿主免疫反应识别自我和非自我的关键第一道防线。TLR9的异常激活与不同自身免疫性疾病中的自身反应性炎症有关。本发明描述的式(I)化合物、组合物和方法可用于多种临床应用，包括作为药物制剂和方法用于治疗因TLR9活化而导致的不需要的免疫活动。
• Protein Lysine Methyltransferase G9a Inhibitors: Design, Synthesis, and Structure Activity Relationships of 2,4-Diamino-7-aminoalkoxy-quinazolines.
  作者：Feng Liu、Xin Chen、Abdellah Allali-Hassani、Amy M. Quinn、Tim J. Wigle、Gregory A. Wasney、Aiping Dong、Guillermo Senisterra、Irene Chau、Alena Siarheyeva、Jacqueline L. Norris、Dmitri B. Kireev、Ajit Jadhav、J. Martin Herold、William P. Janzen、Cheryl H. Arrowsmith、Stephen V. Frye、Peter J. Brown、Anton Simeonov、Masoud Vedadi、Jian Jin

  DOI：10.1021/jm100478y

  日期：2010.8.12

  Protein lysine methyltransferase G9a, which catalyzes methylation of lysine 9 of histone H3 (H3K9) and lysine 373 (K373) of p53, is overexpressed in human cancers. Genetic knockdown of G9a inhibits cancer cell growth, and the dimethylation of p53 K373 results in the inactivation of p53. Initial SAR exploration of the 2,4-diamino-6,7-dimethoxyquinazoline template represented by 3a (BIX01294), a selective small molecule inhibitor of G9a and GLP, led to the discovery of 10 (UNC0224) as a potent G9a inhibitor with excellent selectivity. A high resolution X-ray crystal structure of the G9a-10 complex, the first cocrystal structure of G9a with a small molecule inhibitor, was obtained. On the basis of the structural insights revealed by this cocrystal structure, optimization of the 7-dimethylaminopropoxy side chain of 10 resulted in the discovery of 29 (UNC0321) (Morrison K(i) = 63 pM), which is the first G9a inhibitor with picomolar potency and the most potent G9a inhibitor to date.
• Discovery of a 2,4-Diamino-7-aminoalkoxyquinazoline as a Potent and Selective Inhibitor of Histone Lysine Methyltransferase G9a
  作者：Feng Liu、Xin Chen、Abdellah Allali-Hassani、Amy M. Quinn、Gregory A. Wasney、Aiping Dong、Dalia Barsyte、Ivona Kozieradzki、Guillermo Senisterra、Irene Chau、Alena Siarheyeva、Dmitri B. Kireev、Ajit Jadhav、J. Martin Herold、Stephen V. Frye、Cheryl H. Arrowsmith、Peter J. Brown、Anton Simeonov、Masoud Vedadi、Jian Jin

  DOI：10.1021/jm901543m

  日期：2009.12.24

  SAR exploration of the 2,4-diamino-6,7-dimethoxyquinazoline template led to the discovery of 8 (UNC0224) as it potent and selective G9a inhibitor. A high resolution X-ray crystal structure of the G9a-8 complex, the first cocrystal structure of G9a with a small molecule inhibitor, was obtained. The cocrystal structure validated our binding hypothesis and will enable structure-based design of novel inhibitors. 8 is a useful tool for investigating the biology of G9a and its roles in chromatin remodeling.
• BLOCKING TOLL-LIKE RECEPTOR 9 SIGNALING WITH SMALL MOLECULE ANTAGONIST
  申请人：Council Of Scientific & Industrial Research

  公开号：EP3433249A1

  公开（公告）日：2019-01-30
• [EN] QUINAZOLINE AND QUINOLINE DERIVATIVE COMPOUNDS AS INHIBITORS OF PROLYLPEPTIDASE, INDUCERS OF APOPTOSIS AND CANCER TREATMENT AGENTS<br/>[FR] COMPOSES DERIVES DE QUINAZOLINE ET DE QUINOLINE SERVANT D'INHIBITEURS DE PROLYLPEPTIDASE, D'INDUCTEURS D'APOPTOSE ET D'AGENTS THERAPEUTIQUES ANTICANCEREUX
  申请人：BAYER AG

  公开号：WO2003055866A1

  公开（公告）日：2003-07-10

  Quinazoline or quinoline derivatives of formula: (Formula I and II); wherein Z is CH or N; Y is O or S; X is OR5 or NR5R6; R1, R2, R3, R4, R5 and R6 are as disclosed. Also described is a method for the inhibiting the prolyl peptidase, inducing apoptosis and treating cancer by administering a therapeutically effective amount of compounds of the formula (I) or (II).