4-(4'-hydroxyphenyl)amino-6,7-dimethoxyquinazoline hydrochloride

• 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: 4-(4'-hydroxyphenyl)amino-6,7-dimethoxyquinazoline hydrochloride
• 英文别名: 4-(6,7-dimethoxyquinazolin-4-ylamino)phenol hydrochloride；4-(4-hydroxyanilino)-6,7-dimethoxyquinazoline hydrochloride；4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol;hydrochloride
• 化学式: C₁₆H₁₅N₃O₃*ClH
• 分子量: 333.774
• InChiKey: HNJNNCPPISFBGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.52
• 重原子数：
  23
• 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：
  76.5
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(4'-hydroxyphenyl)amino-6,7-dimethoxyquinazoline hydrochloride 在 二甲基亚砜 、 potassium hydroxide 作用下， 以 水 、 乙腈 为溶剂， 反应 1.25h， 生成
  参考文献：
  名称：

  新型 18F标记取代喹唑啉类化合物及其制备方法 和肿瘤PET显像应用

  摘要：

  本发明提供了一种新型 18 F标记取代喹唑啉类化合物，其特征在于：一端具有 18 F取代烷氧基结构；另一端具有6，7-取代的喹唑啉结构，取代基R 1 位于喹唑啉母体4位上，为2-、3-、4-的 18 F取代烷氧基基团；取代基R 2 位于喹唑啉母体的6位上，为甲氧乙氧基、甲氧基、吗啡啉丙氧基。结构如式A。实验表明，此类化合物具有优良的生物活性，血清稳定性好、在肝脏等组织中摄取较低，在肿瘤中有较高的富集和较慢的清除速率，且同时该类化合物的标记前体易于合成，标记率极高，种种优势，显示此类化合物具有成为肿瘤PET显像的巨大潜力。

  公开号：

  CN103254140B
• 作为产物：
  描述：

  2-氨基-4,5-二甲氧基苯甲酸乙酯 在 三氯氧磷 作用下， 以 异丙醇 、 甲苯 为溶剂， 反应 16.0h， 生成 4-(4'-hydroxyphenyl)amino-6,7-dimethoxyquinazoline hydrochloride
  参考文献：
  名称：

  新型 18F标记取代喹唑啉类化合物及其制备方法 和肿瘤PET显像应用

  摘要：

  本发明提供了一种新型 18 F标记取代喹唑啉类化合物，其特征在于：一端具有 18 F取代烷氧基结构；另一端具有6，7-取代的喹唑啉结构，取代基R 1 位于喹唑啉母体4位上，为2-、3-、4-的 18 F取代烷氧基基团；取代基R 2 位于喹唑啉母体的6位上，为甲氧乙氧基、甲氧基、吗啡啉丙氧基。结构如式A。实验表明，此类化合物具有优良的生物活性，血清稳定性好、在肝脏等组织中摄取较低，在肿瘤中有较高的富集和较慢的清除速率，且同时该类化合物的标记前体易于合成，标记率极高，种种优势，显示此类化合物具有成为肿瘤PET显像的巨大潜力。

  公开号：

  CN103254140B

文献信息

• Quinazoline compounds and pharmaceutical compositions containing them
  申请人：AstraZeneca AB

  公开号：US07081461B1

  公开（公告）日：2006-07-25

  The use of a compound of formula (I) or a salt, ester or amide thereof; where X is O, or S, S(O) or S(O)2, NH or NR8 where R8 is hydrogen or C1-6alkyl; Ra is a 3-quinoline group or a group of sub-formula (i) where R5, R6 and R7 are various specific organic groups, in the preparation of a medicament for use in the inhibtion of aurora 2 kinase. Novel compounds of formula (I) and pharmaceutical compositions useful in the treatment of cancer are also described and claimed.

  使用式（I）的化合物 或其盐、酯或酰胺； 其中X为O、S、S（O）或S（O）2、NH或NR8，其中R8为氢或C1-6烷基； Ra为3-喹啉基团或亚式（i）的基团 其中R5、R6和R7为各种特定的有机基团，在制备用于抑制aurora 2激酶的药物中使用。 还描述和声明了式（I）的新化合物和在癌症治疗中有用的药物组合物。
• KSR antagonists
  申请人：Icahn School of Medicine at Mount Sinai

  公开号：US10548897B2

  公开（公告）日：2020-02-04

  This invention relates to antagonists of Kinase Suppressor of Ras (KSR). Pharmaceutical compositions comprising KSR inhibitors and methods of treating cancer are also provided.

  本发明涉及 Ras 激酶抑制剂（KSR）的拮抗剂。本发明还提供了包含 KSR 抑制剂的药物组合物和治疗癌症的方法。
• The preparation and sar of 4-(anilino), 4-(phenoxy), and 4-(thiophenoxy)-quinazolines: Inhibitors of p56lck and EGF-R tyrosine kinase activity
  作者：Michael R. Myers、Natalie N. Setzer、Alfred.P. Spada、Allison L. Zulli、Chin-Yi J. Hsu、Asher Zilberstein、Susan E. Johnson、Linda E. Hook、Mary V. Jacoski

  DOI：10.1016/s0960-894x(97)00034-6

  日期：1997.2

  We report herein our preliminary results of a SAR study of quinazoline-based inhibitors of p56(lck) and EGF-R tyrosine kinase activity.(1) The most potent inhibitor of p56(lck) identified, RPR-108518A (10), has an IC50 of 0.50 mu M. The 3-chlorophenoxy- and 3-chlorothiophenoxy- derivatives 5 and 6 were also shown to be extremely potent EGF-R inhibitors. (C) 1997, Elsevier Science Ltd.
• WO2020160333A5
  申请人：——

  公开号：WO2020160333A5

  公开（公告）日：2022-12-28
• Virtual screening and synthesis of quinazolines as novel JAK2 inhibitors
  作者：Su Hui Yang、Daulat Bikram Khadka、Suk Hee Cho、Hye-Kyung Ju、Kwang Youl Lee、Ho Jae Han、Kyung-Tae Lee、Won-Jea Cho

  DOI：10.1016/j.bmc.2010.11.057

  日期：2011.1

  JAK2 is an important target in multiple processes associated with tumor growth. In this study, virtual screening was employed for hit compound identification with chemical libraries using SurflexDock. Subsequently, hit optimization for potent and selective candidate JAK2 inhibitors was performed through synthesis of diverse C-1 substituted quinazoline derivatives. A novel compound 5p, (6,7-dimethoxyquinazolin-4-yl)naphthalen-1-ylamine, was thus obtained. JAK2 inhibitory activity of 5p was 43% at 20 mu M and this was comparable to AG490, a representative JAK2 inhibitor. Moreover, 5p showed a positive correlation between JAK2 inhibition and cytotoxicity; 5p treatment in HT-29 cells strongly inhibited JAK2 activation and subsequent STAT3 phosphorylation, reduced anti-apoptotic protein levels, and finally induced apoptosis. This suggests that compound 5p is a candidate inhibitor of JAK2 and its downstream STAT3 signaling pathway for antitumor therapy. In the docking model, the quinazoline template of 5k, the lead compound, occupied a hydrophobic region such as Leu856, Leu855, Ala880, Leu932 and Gly935, and the highly conserved hydrogen bond was created by 6-OMe of the ring template, which binds to the NH of Arg980. Moreover, hydrophobic interactions were identified between morpholine moiety and the hydrophobic region formed by Leu855, Ala880, Tyr931, Val911 and Met929. Also, compound 5k more strongly inhibited JAK2 phosphorylation in mouse embryonic stem cells than AG490. Our study shows the successful application of virtual screening for lead discovery and we propose that the novel compound 5p can be an effective JAK2 inhibitor candidate for further antitumor agent research. (C) 2010 Elsevier Ltd. All rights reserved.