4-氯-6,7-二乙氧基喹唑啉 | 162363-46-4

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 4-氯-6,7-二乙氧基喹唑啉
• 英文名称: 4-Chloro-6,7-diethoxyquinazoline
• CAS: 162363-46-4
• 化学式: C₁₂H₁₃ClN₂O₂
• 分子量: 252.7
• InChiKey: HGMQPDNSSYTATF-UHFFFAOYSA-N

物化性质

• 熔点：
  141-143℃
• 沸点：
  370.3±37.0 °C(Predicted)
• 密度：
  1.245±0.06 g/cm3 (20 ºC 760 Torr)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  4-氯-6,7-二乙氧基喹唑啉 在 氢溴酸 、 溴 作用下， 以 乙醇 、 异丙醇 为溶剂， 反应 3.33h， 生成 (6,7-Diethoxy-quinazolin-4-yl)-[3-(2-phenyl-thiazol-4-yl)-phenyl]-amine
  参考文献：
  名称：

  Anilinoquinazoline Inhibitors of Fructose 1,6-Bisphosphatase Bind at a Novel Allosteric Site:  Synthesis, In Vitro Characterization, and X-ray Crystallography

  摘要：

  The synthesis and in vitro structure-activity relationships (SAR) of a novel series of anilinoquinazolines as allosteric inhibitors of fructose-1,6-bisphosphatase (F16Bpase) are reported. The compounds have a different SAR as inhibitors of F16Bpase than anilinoquinazolines previously reported. Selective inhibition of F16Bpase can be attained through the addition of appropriate polar functional groups at the quinazoline 2-position, thus separating the F16Bpase inhibitory activity from the epidermal growth factor receptor tyrosine kinase inhibitory activity previously observed with similar structures. The compounds have been found to bind at a symmetry-repeated novel allosteric site at the subunit interface of the enzyme. Inhibition is brought about by binding to a loop comprised of residues 52-72, preventing the necessary participation of these residues in the assembly of the catalytic site. Mutagenesis studies have identified the key amino acid residues in the loop that are required for inhibitor recognition and binding.

  DOI：

  10.1021/jm010496a
• 作为产物：
  描述：

  3,4-二乙氧基苯甲酸乙酯 在 10percent Pd/C ammonium carbonate 、 氢气 、 硝酸 、 溶剂黄146 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 25.0~170.0 ℃ 、344.75 kPa 条件下， 反应 8.0h， 生成 4-氯-6,7-二乙氧基喹唑啉
  参考文献：
  名称：

  Anilinoquinazoline Inhibitors of Fructose 1,6-Bisphosphatase Bind at a Novel Allosteric Site:  Synthesis, In Vitro Characterization, and X-ray Crystallography

  摘要：

  The synthesis and in vitro structure-activity relationships (SAR) of a novel series of anilinoquinazolines as allosteric inhibitors of fructose-1,6-bisphosphatase (F16Bpase) are reported. The compounds have a different SAR as inhibitors of F16Bpase than anilinoquinazolines previously reported. Selective inhibition of F16Bpase can be attained through the addition of appropriate polar functional groups at the quinazoline 2-position, thus separating the F16Bpase inhibitory activity from the epidermal growth factor receptor tyrosine kinase inhibitory activity previously observed with similar structures. The compounds have been found to bind at a symmetry-repeated novel allosteric site at the subunit interface of the enzyme. Inhibition is brought about by binding to a loop comprised of residues 52-72, preventing the necessary participation of these residues in the assembly of the catalytic site. Mutagenesis studies have identified the key amino acid residues in the loop that are required for inhibitor recognition and binding.

  DOI：

  10.1021/jm010496a

文献信息

• Metabolic stability of 6,7-dialkoxy-4-(2-, 3- and 4-[18F]fluoroanilino)quinazolines, potential EGFR imaging probes
  作者：Neil Vasdev、Peter N. Dorff、James P. O’Neil、Frederick T. Chin、Stephen Hanrahan、Henry F. VanBrocklin

  DOI：10.1016/j.bmc.2011.03.032

  日期：2011.5

  Epidermal growth factor receptors (EGFR), upregulated in many tumor types, have been a target for therapeutic development and molecular imaging. The objective of this study was to evaluate the distribution and metabolic characteristics of fluorine-18 labeled anilinoquinazolines as potential imaging agents for EGFR tyrosine kinase expression. Fluorine-18 labeled fluoronitrobenzenes were prepared by

  表皮生长因子受体 (EGFR) 在许多肿瘤类型中上调，已成为治疗开发和分子成像的目标。本研究的目的是评估氟 18 标记的苯胺基喹唑啉作为 EGFR 酪氨酸激酶表达的潜在显像剂的分布和代谢特征。氟-18 标记的氟硝基苯是通过穴状和 [ 18 F] 氟化钾与 1,2- 和 1,4- 二硝基苯以及 3-硝基-N , N , N-三甲基苯胺三氟甲磺酸盐在 5 分钟内反应制备的。[ 18 F] 氟化物掺入硝基芳族化合物的衰变校正放射化学产率为81 ± 2%、44 ± 4% 和 77 ± 5% ( n = 3–5) 分别表示 2-、3- 和 4- 氟异构体。硼氢化钠还原为相应的 [ 18 F] 氟苯胺，5 分钟内转化率超过 80%。[偶联18 F]氟苯胺-盐酸盐向6,7-二甲氧基-4-氯喹唑啉，得到相应的6,7-二甲氧基-4-（2-，3-和4- [ 18 F]氟苯胺基）喹唑啉在31 ± 5%、17 ±
• 一种含噻吩磺酰胺结构的乙氧苯并喹唑啉类酪氨酸激酶抑制剂、制备方法及用途
  申请人：浙江医药高等专科学校

  公开号：CN106317039A

  公开（公告）日：2017-01-11

  本发明涉及肿瘤疾病领域。具体而言，本发明涉及一种含噻吩磺酰胺结构的乙氧苯并喹唑啉类酪氨酸激酶抑制剂、其制备方法及其在制备治疗肿瘤疾病中的应用。
• Potent and Selective Inhibitors of Platelet-Derived Growth Factor Receptor Phosphorylation. 3. Replacement of Quinazoline Moiety and Improvement of Metabolic Polymorphism of 4-[4-(<i>N</i>-Substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline Derivatives
  作者：Kenji Matsuno、Junko Ushiki、Takashi Seishi、Michio Ichimura、Neill A. Giese、Jin-Chen Yu、Shusuke Takahashi、Shoji Oda、Yuji Nomoto

  DOI：10.1021/jm020505v

  日期：2003.11.1

  10 microM). Regarding replacements of quinazoline by other heterocyclic rings, pyrazolo[3,4-d]pyrimidine (39a, IC(50) = 0.17 microM) and quinoline (IC(50) of 40a is 0.18 microM; IC(50) of 40b is 0.09 microM) derivatives showed potent activity. Isoquinoline and some pyridopyrimidine derivatives were completely inactive; therefore, 1-aza has an important role. Also 7-aza and 8-aza substitution on the

  我们以前曾报道过，一系列的4- [4-（N-取代的（硫代）氨基甲酰基）-1-哌嗪基] -6,7-二甲氧基喹唑啉衍生物是有效的和选择性的血小板衍生生长因子受体（PDGFR）磷酸化抑制剂。并证明了多种生物学效应，例如通过口服给药抑制大鼠颈动脉球囊损伤后新内膜的形成。在这里，我们研究了6,7-二甲氧基喹唑啉基部分的结构活性关系。关于6,7-二甲氧基，乙氧基类似物显示出有效的活性（16b的IC（50）为0.04 microM； 17a的IC（50）为0.01 microM），烷基的进一步延伸降低了活性。有趣的是，甲氧基乙氧基（16j的IC（50）为0.02 microM; 17h的IC（50）为0.01 microM）和乙氧基乙氧基（17j的IC（50）为0。02 micro M）类似物显示出最有效的活性，表明插入的氧原子与β-PDGFR显着相互作用。在三环喹唑啉衍生物中，2-氧代咪唑并[4,5-
• 一种含噻吩磺酰胺结构的乙氧苯并喹唑啉类酪氨酸激酶抑制剂及用途
  申请人：浙江医药高等专科学校

  公开号：CN106317037A

  公开（公告）日：2017-01-11

  本发明涉及肿瘤疾病领域。具体而言，本发明涉及一种含噻吩磺酰胺结构的乙氧苯并喹唑啉类酪氨酸激酶抑制剂、其制备方法及其在制备治疗肿瘤疾病中的应用。
• Fructose 1,6-bisphosphatase inhibitors
  申请人：——

  公开号：US20030144308A1

  公开（公告）日：2003-07-31

  The present invention relates to certain quinazoline compounds which have utility in the treatment of diabetes mellitus, hypercholesterolemia, hyperlipidemia, diabetic complications and cancer. The invention also relates to pharmaceutical compositions and kits comprising such quinazoline compounds and to methods of using such compounds in the treatment of diabetes mellitus, hypercholesterolemia, hyperlipidemia, diabetic complications and cancer.

  本发明涉及某些喹唑啉化合物，其在糖尿病、高胆固醇血症、高脂血症、糖尿病并发症和癌症治疗中具有用途。该发明还涉及含有这种喹唑啉化合物的药物组合物和配套工具，以及使用这些化合物治疗糖尿病、高胆固醇血症、高脂血症、糖尿病并发症和癌症的方法。