4-氯-6,7-亚甲基二氧基喹唑啉 | 72700-23-3

• 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-亚甲基二氧基喹唑啉
• 英文名称: 8-chloro-[1,3]dioxolo[4,5-g]quinazoline
• 英文别名: 8-chloro-2H-[1,3]dioxolo[4,5-g]quinazoline；4-chloro-6,7-methylenedioxyquinazoline
• CAS: 72700-23-3
• 化学式: C₉H₅ClN₂O₂
• 分子量: 208.604
• InChiKey: RZCJSVRGPHXBSM-UHFFFAOYSA-N

物化性质

• 熔点：
  148-150 °C
• 沸点：
  360.3±37.0 °C(Predicted)
• 密度：
  1.566±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090
• 储存条件：
  存储条件：2-8℃，请保持干燥。

反应信息

• 作为反应物：
  描述：

  4-氯-6,7-亚甲基二氧基喹唑啉 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 异丙醇 、 mineral oil 为溶剂， 反应 24.0h， 生成 4-(N-methyl-3-chloro-4-fluoroanilino)-6,7-methylenedioxyquinazoline
  参考文献：
  名称：

  Design, Synthesis, and DNA-Binding of N-Alkyl(anilino)quinazoline Derivatives

  摘要：

  New N-alkylanilinoquinazoline derivatives 5, 12, 20, and 22 have been prepared Crow 4-chloro-6, 7-dimethoxyquinazoline 3, 4-chloro-6,7-methylenedioxyquinazoline 19, and commercially available anilines. Differents classes of compounds substituted by an aryloxygroup (6a-c. 16a,b, and 17a,b). (aminophenyl)ureas (12a,b and 13a-f), anilines (4a-m, 20a,b), N-alkyl(aniline) (5a-m, 21a,b. 22a,d). and N-aminoalkyl(aniline) (22e-g) have been synthesized. These molecules were evaluated for then. cytotoxic activities and as potential DNA intercalating agents. We studied the strength and mode of binding to DNA of these molecules by DNA melting temperature measurements, fluorescence emission. and circular dichroism. The results of various spectral and gel electrophoresis techniques obtained with the different compounds, in particular compounds 5g and 22f, revealed significant DNA interaction. These experiments confirm that the N-aminoalkyl(anilino)-6,7-dimethoxyquinazoline nucleus is an efficient pharmacophore to trigger binding to DNA, via an intercalative binding process.

  DOI：

  10.1021/jm1009605
• 作为产物：
  描述：

  ethyl (1,3-benzodioxolan-5-yl)carbamate 在 ammonium cerium (IV) nitrate 、 溶剂黄146 、 三乙胺 、 三氟乙酸 、 三氯氧磷 作用下， 以 水 为溶剂， 反应 7.25h， 生成 4-氯-6,7-亚甲基二氧基喹唑啉
  参考文献：
  名称：

  基于喹唑啉的多酪氨酸激酶抑制剂：合成，建模，抗肿瘤和抗血管生成特性

  摘要：

  在这项工作中，报道了一些在喹唑啉支架和苯胺部分带有修饰的新型苯胺喹唑啉衍生物的合成和生物学评估。初步的细胞毒性研究确定了三种衍生物，它们是最有效的化合物，这些衍生物带有稠合在喹唑啉部分和联苯氨基取代基作为苯胺部分的双加氧环。进一步的研究表明，这些化合物通过抑制受体和非受体TK，在多种人类肿瘤细胞系中均表现出抗增殖活性。此外，带有二氧戊环核的化合物也能够在体内抑制肿瘤生长。这些化合物进入激酶结构域的分子模型表明，苯基基团允许与目标蛋白质具有良好的相互作用能：该特征在6,7位上被稠合的双加氧环所支持，而自由旋转功能不允许正确放置分子，从而削弱了抑制效力。最后，联苯氨基衍生物在非细胞毒性浓度下，在体外和体内试验中均作为抗血管生成剂。

  DOI：

  10.1016/j.ejmech.2013.06.057

文献信息

• Alkynyl and azido-substituted 4-anilinoquinazolines
  申请人：Pfizer Inc.

  公开号：US05747498A1

  公开（公告）日：1998-05-05

  The invention relates to compounds of the formula ##STR1## and to pharmaceutically acceptable salts thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, n and m are as defined herein. The compounds of formula I are useful in the treatment of hyperproliferative diseases, such as cancer. The invention further relates to processes of making the compounds of formula I and to methods of using such compounds in the treatment of hyperproliferative diseases.

  该发明涉及公式##STR1##的化合物及其药用盐，其中R.sup.1、R.sup.2、R.sup.3、R.sup.4、n和m如本文所定义。公式I的化合物在治疗高增殖性疾病，如癌症方面是有用的。该发明还涉及制备公式I化合物的方法以及在治疗高增殖性疾病中使用这些化合物的方法。
• [EN] COMPOSITIONS AND METHODS FOR TREATING CANCER<br/>[FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT DU CANCER
  申请人：UNIV CALIFORNIA

  公开号：WO2019067543A1

  公开（公告）日：2019-04-04

  The present disclosure relates to compounds that are capable penetrating to the blood brain barrier to modulate the activity of EGFR tyrosine kinase. The disclosure further relates to methods of treating Glioblastoma and other EGFR mediated cancers. The disclosure further relates to methods of treating Glioblastoma and other EGFR mediated cancers that have been determined to have altered glucose metabolism in the presence of inhibitors. The present dislcsoure also provides methods oadministering to a subject a glucose metabolism inhibitor and a cytoplasmic p53 stabilizer.

  本公开涉及能够穿透血脑屏障以调节EGFR酪氨酸激酶活性的化合物。该公开进一步涉及治疗胶质母细胞瘤和其他EGFR介导的癌症的方法。该公开还涉及治疗已确定在抑制剂存在下具有改变葡萄糖代谢的胶质母细胞瘤和其他EGFR介导的癌症的方法。本公开还提供了向受试者施用葡萄糖代谢抑制剂和细胞质p53稳定剂的方法。
• Exploring Epidermal Growth Factor Receptor (EGFR) Inhibitor Features: The Role of Fused Dioxygenated Rings on the Quinazoline Scaffold
  作者：Adriana Chilin、Maria Teresa Conconi、Giovanni Marzaro、Adriano Guiotto、Luca Urbani、Francesca Tonus、Pierpaolo Parnigotto

  DOI：10.1021/jm901338g

  日期：2010.2.25

  A number of dioxolane, dioxane, and dioxepine quinazoline derivatives have been synthetized and evaluated as EGFR inhibitors. Their cytotoxic activity has been tested against two cell lines overexpressing and not expressing EGFR. Most derivatives were able to counteract EGF-induced EGFR phosphorylation, and their potency was comparable to the reference compound PD153035. The size of the fused dioxygenated

  已经合成了许多二氧戊环，二氧六环和二氧杂环庚烷喹唑啉衍生物，并将其评估为EGFR抑制剂。已经针对两种过表达和不表达EGFR的细胞系测试了它们的细胞毒性活性。大多数衍生物能够抵消EGF诱导的EGFR磷酸化，其效价与参考化合物PD153035相当。稠合的双加氧环的大小对于生物活性至关重要，二恶烷衍生物是该系列中最有前途的一类。
• [EN] NOVEL N-(2,3-DIHYDRO-1H-PYRROLO[2,3-B]JPYRIDIN-5-YL)-4- QUINAZOLINAMINE AND N-(2,3-DIHYDRO-1H-INDOL-5-YL)-4- QUINAZOLINAMINE DERIVATIVES AS PERK INHIBITORS<br/>[FR] DÉRIVÉS N-(2,3-DIHYDRO-1H-PYRROLO[2,3-B]PYRIDIN-5-YL)-4-QUINAZOLINAMINE ET N-(2,3-DIHYDRO-1H-INDOL-5-YL)-4-QUINAZOLINAMINE D'UN NOUVEAU TYPE EN TANT QU'INHIBITEURS DE PERK
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2014161808A1

  公开（公告）日：2014-10-09

  The present invention relates to N-(2,3-dihydro-1H-pyrrolo[2,3-b)]pyridin-5-yl)-4-quinazolinamine and N-(2.3-dihydro-1H-indol-5-yl)-4-quinazolinamine derivatives of Formula (I) wherein R1, R2, R3, R4, R5, R6 and A have the meaning defined in the claims. The compounds according to the present invention are useful as inhibitors of PERK. The invention further relates to processes for preparing such compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

  本发明涉及Formula (I)中的N-(2,3-二氢-1H-吡咯[2,3-b)]吡啶-5-基)-4-喹唑啉胺和N-(2.3-二氢-1H-吲哚-5-基)-4-喹唑啉胺衍生物，其中R1、R2、R3、R4、R5、R6和A的含义如索赔中所定义。根据本发明的化合物可用作PERK的抑制剂。本发明还涉及制备这些化合物的方法、包含上述化合物作为活性成分的药物组合物以及将上述化合物用作药物的用途。
• [EN] NOVEL FUSED HETEROCYCLIC DERIVATIVES USEFUL AS c-MET TYROSINE KINASE INHIBITORS<br/>[FR] NOUVEAUX DÉRIVÉS HÉTÉROCYCLIQUES FUSIONNÉS CONVENANT COMME INHIBITEURS DE C-MET TYROSINE KINASE
  申请人：ZHEJIANG BETA PHARMA INC

  公开号：WO2012006960A1

  公开（公告）日：2012-01-19

  Certain novel fused quinazoline derivatives of formula (I) as c-Met inhibitors, their synthesis and their uses for treating a c-Met mediated disorder. Methods for treating a c-Met-mediated disorder are also disclosed in the invention.

  某些新型融合喹唑啉衍生物的化学式（I），作为c-Met抑制剂，它们的合成以及用于治疗c-Met介导的疾病的用途。该发明还揭示了治疗c-Met介导疾病的方法。