6-methoxy-2-(naphthalen-1-yl)quinazolin-4(3H)-one

• 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-2-(naphthalen-1-yl)quinazolin-4(3H)-one
• 英文别名: 6-Methoxy-2-(naphthalen-1-yl)-4-quinazolinone；6-methoxy-2-naphthalen-1-yl-3H-quinazolin-4-one
• 化学式: C₁₉H₁₄N₂O₂
• 分子量: 302.332
• InChiKey: NLYRGRJWMUBIIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  50.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-甲氧基-2-硝基苯甲酸 在 氯化亚砜 、 palladium 10% on activated carbon 、 氨 、 氢气 、 sodium hydrogensulfite 作用下， 以 甲醇 、 N,N-二甲基乙酰胺 、 1,2-二氯乙烷 为溶剂， 反应 7.0h， 生成 6-methoxy-2-(naphthalen-1-yl)quinazolin-4(3H)-one
  参考文献：
  名称：

  2-Aryl-4-Quinazolinones And Their Pharmaceutical Compositions

  摘要：

  提供的是公式I的化合物或其药用可接受的盐、溶剂化物或立体异构体：其中Ar代表R5、R6、R7、R8、R1'、R2'、R3'、R4'、R5'、R6'、R7'、R8'独立代表H、OH、F、Cl、Br、C1至C6烷基团、C1至C6烷氧基团、C2至C6烯基团、C2至C6烯氧基团、C2至C6炔基团、C2至C6炔氧基团、氨基团、单或二取代氨基团、环状C1至C5烷基氨团、咪唑基团、吗啡啉基团、哌嗪基团，可选择地被一个或多个羟基或卤素取代；X代表NH、O或S。本发明还提供了包含公式I化合物的组合物。根据本发明的化合物和组合物对治疗或缓解疾病或病症有效，如恶性胶质瘤。

  公开号：

  US20130102602A1

文献信息

• A highly efficient heterogeneous palladium-catalyzed carbonylative annulation of 2-aminobenzamides with aryl iodides leading to quinazolinones
  作者：Shengyong You、Bin Huang、Tao Yan、Mingzhong Cai

  DOI：10.1016/j.jorganchem.2018.09.003

  日期：2018.11

  The first heterogeneous carbonylative annulation of 2-aminobenzamides with aryl iodides was achieved in N,N-dimethylformamide (DMF) at 120 °C under 10 bar of carbon monoxide by using an MCM-41-immobilized bidentate phosphine palladium(II) complex [MCM-41-2P-Pd(OAc)2] as catalyst and 1,8-diazabicycloundec-7-ene (DBU) as base, yielding a wide variety of quinazolinone derivatives in good to excellent

  通过使用MCM-41固定的二齿膦膦钯（II）络合物[MCM] ，在N，N-二甲基甲酰胺（DMF）中于120°C，10 bar一氧化碳的条件下，首次实现了2-氨基苯甲酰胺与芳基碘的羰基环化反应。-41-2P-Pd（OAc）2 ]作为催化剂，1,8-二氮杂双环十一碳烯-7（DBU）作为碱，可产生多种喹唑啉酮衍生物，收率良好至极佳。新的多相钯催化剂可以通过简单的方法容易地由市售试剂制备，并通过过滤反应溶液进行回收，并循环使用八次而不会显着降低活性。
• A practical synthesis of quinazolinones via intermolecular cyclization between 2-halobenzamides and benzylamines catalyzed by copper(I) immobilized on MCM-41
  作者：Nan Yan、Chongren You、Mingzhong Cai

  DOI：10.1016/j.jorganchem.2019.07.003

  日期：2019.10

  using an MCM-41-immobilized l-proline copper(I) complex [MCM-41-l-Proline-CuBr] as the catalyst and air as the oxidant, yielding a variety of quinazolinone derivatives in good yields. The new MCM-41-l-Proline-CuBr catalyst can easily be prepared from commercially readily available and inexpensive reagents and recovered by filtration of the reaction mixture, and reused up to seven times with almost consistent

  该非均相串联Ñ -arylation /氧化C-H的2-卤代苯甲酰胺和苄胺的酰胺化在DMSO，在110或120℃下通过使用MCM-41固定来实现升-脯氨酸铜（I）配合物[MCM-41-升-脯氨酸-CuBr]作催化剂，空气作氧化剂，以高收率得到各种喹唑啉酮衍生物。新MCM-41-升-脯氨酸-溴化亚铜催化剂可容易地从市场上容易获得且廉价的试剂和制备通过将反应混合物的过滤回收，并用几乎一致的活性重复使用7次。
• 2-aryl-4-quinazolinones and their pharmaceutical compositions
  申请人：China Medical University

  公开号：US09045437B2

  公开（公告）日：2015-06-02

  Provided is a compound of the formula I or a pharmaceutically acceptable salt, solvate or stereoisomer thereof: wherein Ar represents R5, R7, R8, R2′, R3′, R4′, R5′, R6′, R7′, R8′ independently represent H, OH, F, Cl, Br methoxyl group, NH2 group or NMe2 group; X represents NH, O or S; R6 is selected from the group consisting of: piperidinyl group, morpholino group, methoxyl group, and dimethylamine group. The present invention also provides a composition comprising the compound of formula I. The compound and the composition in accordance with the present invention are effective on treating or alleviating a disease or disorder, such as malignant glioma.

  提供的是式I的化合物或其药学上可接受的盐、溶剂化合物或立体异构体：其中Ar代表R5、R7、R8、R2'、R3'、R4'、R5'、R6'、R7'、R8'，独立地代表H、OH、F、Cl、Br、甲氧基基团、NH2基团或NMe2基团；X代表NH、O或S；R6选自以下组中的一种：哌啶基团、吗啉基团、甲氧基基团和二甲胺基团。本发明还提供了包含式I化合物的组合物。根据本发明，该化合物和组合物对于治疗或缓解疾病或障碍，如恶性胶质瘤，是有效的。
• 2-ARYL-4-QUINAZOLINONES AND THEIR PHARMACEUTICAL COMPOSITIONS
  申请人：China Medical University

  公开号：US20130310376A1

  公开（公告）日：2013-11-21

  Provided is a compound of the formula I or a pharmaceutically acceptable salt, solvate or stereoisomer thereof: wherein Ar represents R 5 , R 7 , R 8 , R 2 ′, R 3 ′, R 4 ′, R 5 ′, R 6 ′, R 7 ′, R 8 ′ independently represent H, OH, F, Cl, Br methoxyl group, NH 2 group or NMe 2 group; X represents NH, O or S; R 6 is selected from the group consisting of: piperidinyl group, morpholino group, methoxyl group, and dimethylamine group. The present invention also provides a composition comprising the compound of formula I. The compound and the composition in accordance with the present invention are effective on treating or alleviating a disease or disorder, such as malignant glioma.

  提供的是公式I的化合物或其药学上可接受的盐、溶剂或立体异构体，其中Ar代表R5、R7、R8、R2'、R3'、R4'、R5'、R6'、R7'、R8'，分别独立地表示H、OH、F、Cl、Br、甲氧基基团、NH2基团或NMe2基团；X代表NH、O或S；R6选自以下组中的一种：哌啶基团、吗啉基团、甲氧基基团和二甲胺基团。本发明还提供了一种包含公式I化合物的组合物。根据本发明，该化合物和组合物对于治疗或缓解疾病或障碍，如恶性胶质瘤，具有良好的疗效。
• Molecular modelling, synthesis, cytotoxicity and anti-tumour mechanisms of 2-aryl-6-substituted quinazolinones as dual-targeted anti-cancer agents
  作者：M J Hour、K H Lee、T L Chen、K T Lee、Yu Zhao、H Z Lee

  DOI：10.1111/bph.12233

  日期：2013.8

  Background and PurposeOur previous study demonstrated that 6‐(pyrrolidin‐1‐yl)‐2‐(3‐methoxyphenyl)quinazolin‐4‐one (HMJ38) was a potent anti‐tubulin agent. Here, HMJ38 was used as a lead compound to develop more potent anti‐cancer agents and to examine the anti‐cancer mechanisms.Experimental ApproachUsing computer‐aided drug design, 2‐aryl‐6‐substituted quinazolinones (MJ compounds) were designed and synthesized by introducing substituents at C‐2 and C‐6 positions of HMJ38. The cytotoxicity of MJ compounds towards human cancer cells was examined by Trypan blue exclusion assay. Microtubule distribution was visualized using TubulinTrackerTM Green reagent. Protein expression of cell cycle regulators and JNK was assessed by Western blot analysis.Key ResultsCompounds MJ65–70 exhibited strong anti‐proliferative effects towards melanoma M21, lung squamous carcinoma CH27, lung non‐small carcinoma H460, hepatoma Hep3B and oral cancer HSC‐3 cells, with one compund MJ66 (6‐(pyrrolidin‐1‐yl)‐2‐(naphthalen‐1‐yl)quinazolin‐4‐one) highly active against M21 cells (IC50 about 0.033 μM). Treatment of CH27 or HSC‐3 cells with MJ65–70 resulted in significant mitotic arrest accompanied by increasing multiple asters of microtubules. JNK protein expression was involved in the MJ65–70‐induced CH27 and M21 cell death. Consistent with the cell cycle arrest at G2/M phase, marked increases in cyclin B1 and Bcl‐2 phosphorylation were also observed, after treatment with MJ65–70.Conclusions and ImplicationMJ65–70 are dual‐targeted, tubulin‐ and JNK‐binding, anti‐cancer agents and induce cancer cell death through up‐regulation of JNK and interfering in the dynamics of tubulin. Our work provides a new strategy and mechanism for developing dual‐targeted anti‐cancer drugs, contributing to clinical anti‐cancer drug discovery and application.