6-(piperidin-1-yl)-2-(benzo[b]thiophen-3-yl)quinazolin-4-one | 1431363-00-6

• 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-(piperidin-1-yl)-2-(benzo[b]thiophen-3-yl)quinazolin-4-one
• 英文别名: MJ-73；6-(Piperidin-1-yl)-2-(benzo[b]thiophen-3-yl)quinazolin-4-one；2-(1-benzothiophen-3-yl)-6-piperidin-1-yl-3H-quinazolin-4-one
• CAS: 1431363-00-6
• 化学式: C₂₁H₁₉N₃OS
• 分子量: 361.467
• InChiKey: ASDXZZFMIKQWAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  72.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-氯-2-硝基苯甲酸 在 氯化亚砜 、 palladium on activated charcoal 、 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 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 6-(piperidin-1-yl)-2-(benzo[b]thiophen-3-yl)quinazolin-4-one
  参考文献：
  名称：

  Molecular modelling, synthesis, cytotoxicity and anti-tumour mechanisms of 2-aryl-6-substituted quinazolinones as dual-targeted anti-cancer agents

  摘要：

  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.

  DOI：

  10.1111/bph.12233

文献信息

• 2-Aryl-4-Quinazolinones And Their Pharmaceutical Compositions
  申请人：Hour Mann-Jen

  公开号：US20130102602A1

  公开（公告）日：2013-04-25

  Provided is a compound of the formula I or a pharmaceutically acceptable salt, solvate or stereoisomer thereof: wherein Ar represents R 5 , R 6 , R 7 , R 8, R 1 ′, R 2 ′, R 3 ′, R 4 ′, R 5 ′, R 6 ′, R 7 ′, R 8 ′ independently represent H, OH, F, Cl, Br, C 1 to C 6 alkyl group, C 1 to C 6 alkoxy group, C 2 to C 6 alkenyl group, C 2 to C 6 alkenoxy group, C 2 to C 6 alkynyl group, C 2 to C 6 alkynoxy group, amine group, mono- or di-substituted amino group, cyclic C 1 to C 5 alkylamino group, imidazolyl group, morpholino group, piperazinyl group, optionally substituted with one or more hydroxy or halo; and X represents NH, O or S. 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。
• 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。
• US9006239B2
  申请人：——

  公开号：US9006239B2

  公开（公告）日：2015-04-14
• US9045437B2
  申请人：——

  公开号：US9045437B2

  公开（公告）日：2015-06-02