N-(3-ethynylphenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine | 936446-61-6

• 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: N-(3-ethynylphenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine
• 英文别名: NRC-2694；N-(3-Ethynylphenyl)-7-methoxy-6-(3-(4-morpholinyl)propoxy)-4-quinazolinamine；N-(3-ethynylphenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine
• CAS: 936446-61-6
• 化学式: C₂₄H₂₆N₄O₃
• 分子量: 418.495
• InChiKey: WBKHQQZRHCECKK-UHFFFAOYSA-N

物化性质

• 沸点：
  597.6±50.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：250 mg/ml（597.39 mM）

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  68.7
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  N-(3-ethynylphenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine 在 盐酸 作用下， 以 异丙醇 为溶剂， 反应 4.0h， 以86.5%的产率得到N-(3-ethynylphenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine dihydrochloride
  参考文献：
  名称：

  [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF N-(3-ETHYNYLPHENYL)-7-METHOXY-6-(3-MORPHOLINOPROPOXY) QUINAZOLIN -4-AMINE DIHYDROCHLORIDE
  [FR] PROCÉDÉ AMÉLIORÉ POUR LA PRÉPARATION DE DICHLORHYDRATE DE N-(3-ÉTHYNYLPHÉNYL)-7-MÉTHOXY-6-(3-MORPHOLINOPROPOXY)QUINAZOLIN-4-AMINE

  摘要：

  本发明涉及一种改进的制备N-(3-乙炔基苯基)-7-甲氧基-6-(3-吗啉基丙氧基)喹唑啉-4-胺二盐酸盐的方法。

  公开号：

  WO2018189747A1
• 作为产物：
  描述：

  7-甲氧基-6-(3-吗啉-4-基丙氧基)喹唑啉-4(3H)-酮 在 三氯氧磷 作用下， 以 异丙醇 为溶剂， 反应 18.0h， 生成 N-(3-ethynylphenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine
  参考文献：
  名称：

  吉非替尼-1,2,3-三唑衍生物的合成及体外抗肿瘤活性评价

  摘要：

  在这项研究中，利用点击化学方法合成了 14 种结构新颖的吉非替尼-1,2,3-三唑衍生物，并通过 1H NMR、13C NMR 和高分辨率质谱 (HRMS) 进行了表征。细胞计数试剂盒8的初步结果表明，大多数化合物对表皮生长因子受体野生型肺癌细胞NCI-H1299、A549和NCI-H1437表现出优异的抗肿瘤活性。其中4b和4c表现出最显着的抑制作用。 4b 的半数抑制浓度 (IC50) 值为 4.42 ± 0.24 μM (NCI-H1299)、3.94 ± 0.01 μM (A549) 和 1.56 ± 0.06 μM (NCI-1437)。 4c 的 IC50 值为 4.60 ± 0.18 µM (NCI-H1299)、4.00 ± 0.08 µM (A549) 和 3.51 ± 0.05 µM (NCI-H1437)。此外，我们的结果表明，4b和4c能够以浓度依赖性方式有效抑制增

  DOI：

  10.3390/molecules29040837

文献信息

• METHODS OF TREATING DRUG RESISTANT AND OTHER TUMORS BY ADMINISTERING 6,7-DIALKOXY QUINAZOLINE DERIVATIVES
  申请人：ADIBHATLA KALI SATYA Bhujanga rao

  公开号：US20110028473A1

  公开（公告）日：2011-02-03

  Methods employing and uses of a compound of formula (I) in inhibiting the growth of a tumor cell in a subject in need thereof. Methods employing and uses of a compound of formula (I) in treating pancreatic cancer in a subject in need of treatment for pancreatic cancer. Methods employing and uses of a compound of formula (I) in treating HER-2 positive breast cancer in a subject in need of treatment for HER-2 positive breast cancer. Methods employing and uses of a compound of formula (I) in treating drug resistant non-small cell lung cancer in a subject in need of treatment for drug resistant non-small cell lung cancer. Each of these methods can include administering to the subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. Method of manufacturing a medicament including a compound of formula (I) for treating a subject suffering from growth of a tumor cell; for treating a subject suffering from pancreatic cancer; for treating a subject suffering from HER-2 positive breast cancer; or for treating a subject suffering from drug resistant non-small cell lung cancer.

  使用和利用式(I)化合物的方法，在需要抑制肿瘤细胞生长的受试者中使用。使用和利用式(I)化合物的方法，在需要治疗胰腺癌的受试者中使用。使用和利用式(I)化合物的方法，在需要治疗HER-2阳性乳腺癌的受试者中使用。使用和利用式(I)化合物的方法，在需要治疗耐药非小细胞肺癌的受试者中使用。这些方法可以包括向受试者施用式(I)化合物或其药用盐的有效量。制造一种包括式(I)化合物的药物的方法，用于治疗患有肿瘤细胞生长的受试者；用于治疗患有胰腺癌的受试者；用于治疗患有HER-2阳性乳腺癌的受试者；或用于治疗患有耐药非小细胞肺癌的受试者。
• 6-7,DIALKOXY QUINAZOLINE DERIVATIVES USEFUL FOR TREATMENT OF CANCER RELATED DISORDERS
  申请人：Jyothi Prasad Ramanadham

  公开号：US20110039844A1

  公开（公告）日：2011-02-17

  In view of the great potential the quinazoline class of compounds offer, we started the synthesis and screening of a large number of new chemical entities with novel structural features. It has been surprisingly and unexpectedly found that quinazolines having 3-Ethynyl anilino group at the 4th position and specifically substituted alkoxy groups in the 6 and 7 positions, impart much enhanced and special anti-proliferative properties when compared to other prominent members of the quinazoline class of drugs. Also, surprisingly the compounds of this invention are much less toxic and the safety profile is exceedingly beneficial for therapeutic applications. The novel chemical entities described in this invention are designated by the general structure (I) and have not been synthesized earlier nor investigated for their therapeutic benefits and safety profile. Compound (I) is NRC-2694, when structure (A).

  鉴于喹嗪啉类化合物具有巨大的潜力，我们开始合成和筛选大量具有新结构特征的新化学实体。令人惊讶和意外的发现，喹嗪啉在第4位具有3-乙炔基苯胺基团，并在第6位和第7位具有特定取代的烷氧基团时，与喹嗪啉类药物的其他突出成员相比，具有更强的抗增殖特性。此外，令人惊讶的是，本发明的化合物毒性更低，安全性极高，非常适合治疗应用。本发明中描述的新化学实体由通式（I）表示，以前尚未合成，也没有研究其治疗效益和安全性。当通式（A）时，化合物（I）为NRC-2694。
• 6,7-DIALKOXY QUINAZOLINE DERIVATIVES AND METHODS OF TREATING DRUG RESISTANT AND OTHER TUMORS
  申请人：NATCO PHARMA LIMITED

  公开号：US20170079983A1

  公开（公告）日：2017-03-23

  Methods of inhibiting a receptor tyrosine kinase in a subject in need thereof. Methods of inhibiting the growth of a tumor cell in a subject in need thereof. Methods of treating pancreatic cancer in a subject in need of treatment for pancreatic cancer. Methods of treating HER2 positive breast cancer in a subject in need of treatment for HER2 positive breast cancer. Methods of treating drug resistant non-small cell lung cancer in a subject in need of treatment for drug resistant non-small cell lung cancer. Each of these methods can include administering to the subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof.

  抑制受体酪氨酸激酶在需要的受试者中的方法。抑制肿瘤细胞在需要的受试者中的生长的方法。治疗胰腺癌在需要治疗胰腺癌的受试者中的方法。治疗HER2阳性乳腺癌在需要治疗HER2阳性乳腺癌的受试者中的方法。治疗耐药性非小细胞肺癌在需要治疗耐药性非小细胞肺癌的受试者中的方法。这些方法中的每一种都可以包括向受试者施用公式（I）的化合物或其药学上可接受的盐的有效量。
• 6,7-dialkoxy quinazoline derivatives and methods of treating drug resistant and other tumors
  申请人：Adibhatla Kali Satya Bhujanga rao

  公开号：US08921362B2

  公开（公告）日：2014-12-30

  Compounds of formula (I) in which: R1 is: R2 is —CH3 or —CH2CH3; or a pharmaceutically acceptable salt thereof. Pharmaceutical compositions including the compound of formula (I) and a pharmaceutically acceptable carrier. Processes for preparing the compound of formula (I). Methods of inhibiting a receptor tyrosine kinase in a subject in need thereof. Methods of inhibiting the growth of a tumor cell in a subject in need thereof. Methods of treating pancreatic cancer in a subject in need of treatment for pancreatic cancer. Methods of treating HER2 positive breast cancer in a subject in need of treatment for HER2 positive breast cancer. Methods of treating drug resistant non-small cell lung cancer in a subject in need of treatment for drug resistant non-small cell lung cancer. Each of these methods can include administering to the subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof.

  化合物的式子（I），其中：R1是：R2是—CH3或—CH2CH3；或其药学上可接受的盐。药物组合物包括式子（I）的化合物和药学上可接受的载体。制备式子（I）的化合物的方法。抑制受体酪氨酸激酶的方法，用于需要该方法的受体酪氨酸激酶抑制剂的主体。抑制肿瘤细胞生长的方法，用于需要该方法的受体酪氨酸激酶抑制剂的主体。治疗胰腺癌的方法，用于需要胰腺癌治疗的主体。治疗HER2阳性乳腺癌的方法，用于需要HER2阳性乳腺癌治疗的主体。治疗耐药性非小细胞肺癌的方法，用于需要耐药性非小细胞肺癌治疗的主体。这些方法中的每一种都可以包括向主体施用化合物的有效量式子（I）或其药学上可接受的盐。
• 6,7-DIALKOXY QUINAZOLINE DERIVATIVES USEFUL FOR TREATMENT OF CANCER RELATED DISORDERS
  申请人：Natco Pharma Limited

  公开号：EP3012251A1

  公开（公告）日：2016-04-27

  In view of the great potential the quinazoline class of compounds offer, we started the synthesis and screening of a large number of new chemical entities with novel structural features. It has been surprisingly and unexpectedly found that quinazolines having 3- Ethynyl anilino group at the 4th position and specifically substituted alkoxy groups in the 6 and 7 positions, impart much enhanced and special anti-proliferative properties when compared to other prominent members of the quinazoline class of drugs. Also, surprisingly the compounds of this invention are much less toxic and the safety profile is exceedingly beneficial for therapeutic applications. The novel chemical entities described in this invention are designated by the general structure (I) and have not been synthesized earlier nor investigated for their therapeutic benefits and safety profile.; Compund (I) is NRC-2694, when structure (A).

  鉴于喹唑啉类化合物的巨大潜力，我们开始合成和筛选大量具有新结构特征的新化学实体。我们出人意料地发现，与喹唑啉类药物的其他主要成员相比，在第 4 位具有 3- 乙炔基苯胺基团、在第 6 和第 7 位具有特定取代烷氧基基团的喹唑啉类化合物具有更强、更特殊的抗增殖特性。此外，令人惊讶的是，本发明的化合物毒性更低，其安全性对治疗应用极为有利。本发明中所述的新型化学实体以一般结构（I）表示，此前尚未合成，也未对其治疗效果和安全性进行研究。