4-(1,4-diazepan-1-yl)-6,7-dimethoxyquinazoline

• 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-(1,4-diazepan-1-yl)-6,7-dimethoxyquinazoline
• 英文别名: 4-(Hexahydro-1H-1,4-diazepin-1-yl)-6,7-dimethoxyquinazoline
• 化学式: C₁₅H₂₀N₄O₂
• 分子量: 288.349
• InChiKey: CCGHJMAPPPBZPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  59.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(1,4-diazepan-1-yl)-6,7-dimethoxyquinazoline 在 lithium hydroxide monohydrate 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 2-(4-(6,7-dimethoxyquinazolin-4-yl)-1,4-diazepan-1-yl)ethan-1-amine
  参考文献：
  名称：

  [EN] INHIBITORS OF ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 (ENPP1) AND METHODS OF USE THEREOF
  [FR] INHIBITEURS DE L'ECTONUCLÉOTIDE PYROPHOSPHATASE/PHOSPHODIESTÉRASE 1 (ENPP1) ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  化合物及其制备和使用方法，用作治疗或预防剂，例如通过靶向胞苷酸焦磷酸酶/磷酸二酯酶-1（ENPP1）来治疗癌症、细菌或病毒性疾病。

  公开号：

  WO2021158829A1
• 作为产物：
  描述：

  2-氨基-4,5-二甲氧基苯甲酸 在 氯化亚砜 、 三乙胺 作用下， 以 乙二醇甲醚 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 4-(1,4-diazepan-1-yl)-6,7-dimethoxyquinazoline
  参考文献：
  名称：

  Discovery and Characterization of the Potent and Highly Selective (Piperidin-4-yl)pyrido[3,2-d]pyrimidine Based in Vitro Probe BAY-885 for the Kinase ERK5

  摘要：

  The availability of a chemical probe to study the role of a specific domain of a protein in a concentration- and time-dependent manner is of high value. Herein, we report the identification of a highly potent and selective ERK5 inhibitor BAY-885 by high-throughput screening and subsequent structure-based optimization. ERK5 is a key integrator of cellular signal transduction, and it has been shown to play a role in various cellular processes such as proliferation, differentiation, apoptosis, and cell survival. We could demonstrate that inhibition of ERKS kinase and transcriptional activity with a small molecule did not translate into antiproliferative activity in different relevant cell models, which is in contrast to the results obtained by RNAi technology.

  DOI：

  10.1021/acs.jmedchem.8b01606

文献信息

• Nitrogen-containing heterocyclic compounds
  申请人：——

  公开号：US20020068734A1

  公开（公告）日：2002-06-06

  The present invention provides nitrogen-containing heterocyclic compounds and pharmaceutically acceptable salts thereof which inhibit phosphorylation of PDGF receptor to hinder abnormal cell growth and cell wandering and thus are useful for the prevention or treatment of cell-proliferative diseases such as arteriosclerosis, vascular reobstruction, cancer and glomerulosclerosis. The compounds are represented by general formula (I): 1 wherein V represents an oxygen atom or a sulfur atom; W represents 1,4-piperazinediyl or 1,4-homopiperazinediyl in which carbons on the ring may be substituted by unsubstituted alkyl groups; X represents a nitrogen atom or C-R 9 ; Y represents a nitrogen atom or C-R 8 ; Z represents a nitrogen atom or C-R 7 (provided that at least one of X, Y and Z represents a nitrogen atom); R 1 represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic alkyl group, etc.; R 2 represents a substituted alkyl group, a substituted or unsubstituted alicyclic alkyl group, etc.; R 3 , R 4 , R 5 and R 6 , which may be the same or different, each represents a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl group, a nitro group, a cyano group, OR 12 , —NR 15 R 16 , etc.; R 7 represents a halogen atom, etc.; R 8 has the same significance as R 7 , and R 9 represents a hydrogen atom or —COR 41 .

  本发明提供了含氮杂环化合物及其药学上可接受的盐，其抑制PDGF受体的磷酸化，以阻碍异常细胞生长和细胞游走，因此可用于预防或治疗细胞增殖性疾病，如动脉硬化、血管再狭窄、癌症和肾小球硬化。所述化合物由通式（I）表示：其中V表示氧原子或硫原子；W表示1,4-哌嗪基或1,4-同源哌嗪基，其中环上的碳可以被未取代的烷基取代；X表示氮原子或C-R9；Y表示氮原子或C-R8；Z表示氮原子或C-R7（前提是X、Y和Z中至少有一个表示氮原子）；R1表示氢原子、取代或未取代的烷基、取代或未取代的脂环烷基等；R2表示取代的烷基、取代或未取代的脂环烷基等；R3、R4、R5和R6，可以相同也可以不同，每个表示氢原子、卤素原子、取代或未取代的烷基、硝基、氰基、OR12、—NR15R16等；R7表示卤素原子等；R8具有与R7相同的意义，且R9表示氢原子或—COR41。
• NITROGENOUS HETEROCYCLIC COMPOUNDS
  申请人：KYOWA HAKKO KOGYO KABUSHIKI KAISHA

  公开号：EP0882717A1

  公开（公告）日：1998-12-09

  The present invention provides nitrogen-containing heterocyclic compounds and pharmaceutically acceptable salts thereof which inhibit phosphorylation of PDGF receptor to hinder abnormal cell growth and cell wandering and thus are useful for the prevention or treatment of cell-proliferative diseases such as arteriosclerosis, vascular reobstruction, cancer and glomerulosclerosis. The compounds are represented by general formula (I): wherein V represents an oxygen atom or a sulfur atom; W represents 1,4-piperazinediyl or 1,4-homopiperazinediyl in which carbons on the ring may be substituted by unsubstituted alkyl groups; X represents a nitrogen atom or C-R9; Y represents a nitrogen atom or C-R8; Z represents a nitrogen atom or C-R7 (provided that at least one of X, Y and Z represents a nitrogen atom); R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic alkyl group, etc.; R2 represents a substituted alkyl group, a substituted or unsubstituted alicyclic alkyl group, etc.; R3, R4, R5 and R6, which may be the same or different, each represents a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl group, a nitro group, a cyano group, - OR12, -NR15R16, etc.; R7 represents a halogen atom, etc.; R8 has the same significance as R7, and R9 represents a hydrogen atom or -COR41.

  本发明提供了含氮杂环化合物及其药学上可接受的盐类，它们能抑制 PDGF 受体的磷酸化，从而阻碍细胞的异常生长和游走，因此可用于预防或治疗细胞增殖性疾病，如动脉硬化、血管再阻塞、癌症和肾小球硬化症。这些化合物由通式 (I) 表示： 其中 V 代表氧原子或硫原子； W 代表 1,4-哌嗪二基或 1,4-高哌嗪二基，其中环上的碳可被未取代的烷基取代； X 代表氮原子或 C-R9； Y 代表氮原子或 C-R8 Z 代表氮原子或 C-R7（条件是 X、Y 和 Z 中至少有一个代表氮原子）； R1 代表氢原子、取代或未取代的烷基、取代或未取代的脂环烷基等； R2 代表取代的烷基、取代或未取代的脂环烷基等； R3、R4、R5 和 R6 可以相同或不同，各自代表氢原子、卤素原子、取代或未取代的烷基、硝基、氰基、- OR12、-NR15R16 等； R7 代表卤素原子等； R8 与 R7 意义相同，以及 R9 代表氢原子或-COR41。
• Potent and Selective Inhibitors of PDGF Receptor Phosphorylation. 2. Synthesis, Structure Activity Relationship, Improvement of Aqueous Solubility, and Biological Effects of 4-[4-(<i>N</i>-Substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline Derivatives
  作者：Kenji Matsuno、Takao Nakajima、Michio Ichimura、Neill A. Giese、Jin-Chen Yu、Nathalie A. Lokker、Junko Ushiki、Shin-ichi Ide、Shoji Oda、Yuji Nomoto

  DOI：10.1021/jm0201114

  日期：2002.9.1

  4-[4-(N-Substituted(thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives such as KN1022 are potent inhibitors of the phosphorylation of platelet derived growth factor receptor (PDGFR). Structure activity relationships in the (thio)urea moiety, the phenyl ring itself, the linker between these two moieties, and the piperazine moiety were investigated. The role of the linker was found to be quite different, where ureas yielded decreasing activity, while thioureas provided increasing activity. Cyanoguanidine as a bioisostere of thiourea and related dicyanovinyl or nitrovinyl groups were not suitable for potent activity. A hydrogen atom on the (thio)urea moiety was essential for activity. Stereochemistry was also important for inhibition of PDGFR phosphorylation. Through the modification of these moieties, benzylthiourea analogues with a small substituent on the 4-position and the 3,4-methylenedioxy group (KN734/CT52923) were found to be optimal for selective and potent activity. Replacement of the phenyl ring by heterocycles improved aqueous solubility without loss of activity and kinase selectivity. Introduction of a methyl group on 5-position of the piperazine ring and replacement by homopiperazine reduced inhibitory activity. An efficient synthetic method was also developed for 2-pyridylurea-containing analogues, via carbonylation of 2-aminopyridine with N,N'-carbonyldiimidazole. A potent analogue, KN734, inhibited smooth muscle cell proliferation and migration induced by platelet derived growth factor-BB (PDGF-BB) and suppressed neointima formation following balloon injury in rat carotid artery by oral administration. Therefore, 4-[4(N-substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives may be expected to have potential as therapeutic agents for the treatment of restenosis.
• INHIBITORS OF ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 (ENPP1) AND METHODS OF USE THEREOF
  申请人：Stingray Therapeutics, Inc.

  公开号：EP4100394A1

  公开（公告）日：2022-12-14
• US6169088B1
  申请人：——

  公开号：US6169088B1

  公开（公告）日：2001-01-02