6,7-二甲氧基-4-哌嗪-1-基-喹唑啉 | 21584-72-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 6,7-二甲氧基-4-哌嗪-1-基-喹唑啉
• 英文名称: 6,7-dimethoxy-4-(piperazin-1-yl)quinazoline
• 英文别名: 4-(1-piperazinyl)-6,7-dimethoxyquinazoline；6,7-dimethoxy-4-(1-piperazinyl)quinazoline；6,7-Dimethoxy-4-piperazin-1-yl-quinazoline；6,7-dimethoxy-4-piperazin-1-ylquinazoline
• CAS: 21584-72-5
• 化学式: C₁₄H₁₈N₄O₂
• 分子量: 274.323
• InChiKey: HGQPTOFRZXUHHS-UHFFFAOYSA-N

物化性质

• 沸点：
  462.2±40.0 °C(Predicted)
• 密度：
  1.212±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  59.5
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2933990090
• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  6,7-二甲氧基-4-哌嗪-1-基-喹唑啉 在 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 4-(6,7-Dimethoxy-4-quinazolinyl)-N-(thien-3-ylmethyl)-1-piperazinecarboxamide
  参考文献：
  名称：

  Potent and Selective Inhibitors of PDGF Receptor Phosphorylation. 2. Synthesis, Structure Activity Relationship, Improvement of Aqueous Solubility, and Biological Effects of 4-[4-(N-Substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline Derivatives

  摘要：

  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.

  DOI：

  10.1021/jm0201114
• 作为产物：
  描述：

  4-氯-6,7-二甲氧基喹唑啉 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 12.0h， 生成 6,7-二甲氧基-4-哌嗪-1-基-喹唑啉
  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

• Novel N-acylated heterocycles
  申请人：Recordati S.A.

  公开号：US20030162777A1

  公开（公告）日：2003-08-28

  Described are compositions comprising a muscarinic receptor antagonist and an N-acylated heterocycle derivative having affinity for serotonergic receptors, and enantiomers, diastereoisomers, N-oxides, polymorphs, solvates and pharmaceutically acceptable salts thereof. The combination of a muscarinic receptor antagonist and an N-acylated heterocycle, or an enantiomer, diastereoisomer, N-oxide, polymorph, solvate or pharmaceutically acceptable salt thereof, is useful in the treatment of patients with neuromuscular dysfunction of the lower urinary tract and diseases related to 5-HT 1A receptors.

  描述了包含一种肌氨酸受体拮抗剂和一种对5-HT 1A 受体具有亲和力的N-酰化杂环衍生物的组合物，以及它们的对映体、二对映体、N-氧化物、多型体、溶剂合物和药用可接受盐。肌氨酸受体拮抗剂和N-酰化杂环，或其对映体、二对映体、N-氧化物、多型体、溶剂合物或药用可接受盐的组合，在治疗患有下尿路神经肌肉功能障碍和与5-HT 1A 受体相关疾病的患者中是有用的。
• [EN] ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP-1) INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ECTONUCLÉOTIDE PYROPHOSPHATASE-PHOSPHODIESTÉRASE (ENPP-1) ET UTILISATIONS DE CES DERNIERS
  申请人：MAVUPHARMA INC

  公开号：WO2019046778A1

  公开（公告）日：2019-03-07

  Disclosed herein are methods and compounds of augmenting and enhancing the production of type I IFNs in vivo. In some embodiments, the compounds disclosed herein are ENPP-1 inhibitors, pharmaceutical compositions, and methods for the treatment of cancer or a viral infection.

  本文揭示了一种增强和促进体内I型干扰素产生的方法和化合物。在某些实施例中，本文所披露的化合物是ENPP-1抑制剂，药物组合物，以及用于治疗癌症或病毒感染的方法。
• Inhibition studies on Mycobacterium tuberculosis N-acetylglucosamine-1-phosphate uridyltransferase (GlmU)
  作者：Anh Thu Tran、Daying Wen、Nicholas P. West、Edward N. Baker、Warwick J. Britton、Richard J. Payne

  DOI：10.1039/c3ob41896k

  日期：——

  Peptidoglycan is an essential component of the cell wall of bacteria, including Mycobacterium tuberculosis, that provides structural strength and rigidity to enable internal osmotic pressure to be withstood. The first committed step in the biosynthesis of peptidoglycan involves the formation of uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) from uridine triphosphate (UTP) and GlcNAc-1-phosphate. This reaction is catalysed by N-acetylglucosamine-1-phosphate uridyltransferase (GlmU), a bifunctional enzyme with two independent active sites that possess acetyltransferase and uridyltransferase activities. Herein, we report the first inhibition study targeted against the uridyltransferase activity of M. tuberculosis GlmU. A number of potential inhibitors were initially prepared leading to the discovery of active aminoquinazoline-based compounds. The most potent inhibitor in this series exhibited an IC50 of 74 μM against GlmU uridyltransferase activity and serves as a promising starting point for the discovery of more potent inhibitors.

  肽聚糖是细菌细胞壁的重要组成部分，包括结核分枝杆菌，它为细胞提供结构强度和刚性，以抵御内部渗透压。肽聚糖生物合成中的第一个关键步骤是尿苷二磷酸-N-乙酰氨基葡萄糖（UDP-GlcNAc）从尿苷三磷酸（UTP）和GlcNAc-1-磷酸形成。此反应由N-乙酰氨基葡萄糖-1-磷酸尿苷转移酶（GlmU）催化，GlmU是一种双功能酶，具有两个独立的活性位点，分别具备乙酰转移酶和尿苷转移酶活性。在此，我们报告了针对结核分枝杆菌GlmU的尿苷转移酶活性的首次抑制研究。最初准备了一些潜在抑制剂，导致发现了活性氨基喹唑啉类化合物。在这一系列中，最有效的抑制剂对GlmU尿苷转移酶活性的IC50为74μM，是发现更高效抑制剂的良好起点。
• Potent and Selective Inhibitors of Platelet-Derived Growth Factor Receptor Phosphorylation. 1. Synthesis, Structure−Activity Relationship, and Biological Effects of a New Class of Quinazoline Derivatives
  作者：Kenji Matsuno、Michio Ichimura、Takao Nakajima、Keiko Tahara、Shigeki Fujiwara、Hiroshi Kase、Junko Ushiki、Neill A. Giese、Anjali Pandey、Robert M. Scarborough、Nathalie A. Lokker、Jin-Chen Yu、Junko Irie、Eiji Tsukuda、Shin-ichi Ide、Shoji Oda、Yuji Nomoto

  DOI：10.1021/jm010428o

  日期：2002.7.1

  A new series of 4-[4-(N-substituted carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives were found to show potent and selective inhibition of platelet-dervied growth factor (PDGF) receptor phosphorylation. In this exploration of the structure-activity relationships (SARs) of the prototype inhibitor KN1022, the 4-nitrophenylurea moiety was probed. We found that 4-substitution on the phenyl

  发现一系列新的4- [4-（N-取代的氨基甲酰基）-1-哌嗪基] -6,7-二甲氧基喹唑啉衍生物显示出有效和选择性抑制血小板衍生的生长因子（PDGF）受体磷酸化的作用。在探索原型抑制剂KN1022的构效关系（SAR）时，探测了4-硝基苯基脲部分。我们发现在苯环上的4-取代是最佳的，在苯环上引入两个以上的取代基会降低活性。苯环上的大取代基增强了活性。还制备了硫脲类似物，发现SAR与尿素衍生物略有不同。通过这项研究，我们获得了一些有效的KN1022衍生物，例如4-（4-甲基苯氧基）苯基（36，IC（50）0.02 micromol / L），4-叔丁基苯基（16，IC（50）0。03 micromol / L）和4-苯氧基苯基（21，IC（50）0.08 micromol / L）类似物，其抗KN1022活性增加了近10倍。这些有效的化合物保留了对PDGF受体家族的高选择性，类似于KN1022
• 一种喹啉、喹唑啉类化合物及其药物组合物和应用
  申请人：谢阳

  公开号：CN106083715A

  公开（公告）日：2016-11-09

  本发明公开了通式I所示的喹啉、喹唑啉类化合物及其药学上可接受的盐、氮氧化物、溶剂化物以及包括其各种比例混合物在内的立体异构体，R1、R2、R3、R4、RA、RB、Z1、Z2，X1、X2、X3、D、L、A环、B环、m、n具有在说明书中给出的含义。本发明还涉及此类化合物的制备方法，并且还涉及该类化合物其药学上可接受的盐、氮氧化物、溶剂化物、各种比例混合物在内的立体异构体的用途，特别是在制备用于防护、处理、治疗或减轻癌症病症的药物中的用途。