2-chloro-6,7-dimethoxy-4-(N-morpholino)quinazoline | 39217-02-2

• 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: 2-chloro-6,7-dimethoxy-4-(N-morpholino)quinazoline
• 英文别名: 4-(2-chloro-6,7-dimethoxyquinazolin-4-yl)morpholine；2-chloro-6,7-dimethoxy-4-morpholin-4-yl-quinazoline；2-Chloro-6,7-dimethoxy-4-(4-morpholinyl)quinazoline
• CAS: 39217-02-2
• 化学式: C₁₄H₁₆ClN₃O₃
• 分子量: 309.752
• InChiKey: WTXAUEOICBJOQY-UHFFFAOYSA-N

物化性质

• 熔点：
  221-222 °C(Solv: ligroine (8032-32-4); ethyl acetate (141-78-6))
• 沸点：
  446.0±45.0 °C(Predicted)
• 密度：
  1.327±0.06 g/cm3(Predicted)
• 溶解度：
  13.1 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  56.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-chloro-6,7-dimethoxy-4-(N-morpholino)quinazoline 、 4-乙酰基氨基苯硼酸频哪醇酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 2.0h， 生成 N-(4-(6,7-dimethoxy-4-morpholinoquinazolin-2-yl)phenyl)acetamide
  参考文献：
  名称：

  Synthesis and antitumor activities evaluation of m-(4-morpholinoquinazolin-2-yl)benzamides in vitro and in vivo

  摘要：

  In the present study, a series of m-(4-morpholinoquinazolin-2-yl)benzamides were designed, synthesized and characterized. The antiproliferative activities of the synthesized compounds were evaluated against two human cell lines (HCF-116 and MCF-7). Compounds with IC50 values below 4 mu M were further evaluated against U-87 MG and A549 cell lines. Among these evaluated compounds, compound T10 displayed a remarkable antiproliferative effect in vitro. The hoechst staining assay showed that compound T10 caused morphological changes. The cell cycle and apoptosis assay further indicated that compound T10 can arrest HCT-116 cells in G2/M and G0/G1 phase and induce apoptosis. PI3K enzyme assays indicated that compounds 17 and T10 selectively inhibit PI3K alpha. A Western bolt assay further suggested that compound T10 can block the PI3K/Akt/mTOR pathway. Moreover, compound T10 inhibited tumor growth on a mice S180 homograft model. These findings directly identify m-(4-morpholinoquinazolin-2-yl)benzamide derivatives as novel anticancer agents. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.04.037
• 作为产物：
  描述：

  吗啉 、 2,4-二氯-6,7-二甲氧基喹唑啉 以 甲醇 为溶剂， 反应 1.0h， 以97%的产率得到2-chloro-6,7-dimethoxy-4-(N-morpholino)quinazoline
  参考文献：
  名称：

  激活Transport-P所需的prazosin分子的分子特征。

  摘要：

  已经合成了哌唑嗪的紧密相关的结构类似物，并测试了其对Transport-P的抑制和激活，以鉴定似乎对于激活Transport-P必不可少的Prazosin分子的结构特征。到目前为止，所有测试的化合物都没有比哌唑嗪具有更高的活性。结果表明，哌唑嗪的结构似乎对激活非常特异。已发现仅喹唑啉可活化，并且6,7-二甲氧基和4-氨基的存在似乎至关重要。

  DOI：

  10.1016/j.bmc.2008.06.037

文献信息

• Suzuki–Miyaura cross-coupling reaction of aryl and heteroaryl pinacol boronates for the synthesis of 2-substituted pyrimidines
  作者：Shigehiro Asano、Seiji Kamioka、Yoshiaki Isobe

  DOI：10.1016/j.tet.2011.10.057

  日期：2012.1

  Suzuki–Miyaura cross-coupling reaction with 2-heteroarylboronic acids is generally challenging due to these acids easy decomposition. To overcome this problem, we developed a coupling method that uses 2-heteroaryl pinacol boronates in the presence of 1.0 mol % Pd(OAc)2 and 2.0 mol % S-Phos with 4 equiv amount of LiOH in dioxane and H2O at 80 °C for 30 min. This developed method allowed for the synthesis

  由于这些酸易于分解，因此与2-杂芳基硼酸的铃木-宫浦交叉偶联反应通常具有挑战性。为克服此问题，我们开发了一种偶合方法，该方法在1.0 mol％Pd（OAc）2和2.0 mol％S-Phos的存在下，在80％的二恶烷和H 2 O中于80摩尔下使用2-杂芳基频哪醇硼酸酯°C 30分钟。这种发达的方法允许从2-氯嘧啶基衍生物高产率地合成各种各样的2-杂芳基嘧啶，并且还可以用于由杂芳基氯化物制备各种联芳基衍生物。
• Pyrimidine, quinazoline, pteridine and triazine derivatives
  申请人：Binggeli Alfred

  公开号：US20070225271A1

  公开（公告）日：2007-09-27

  This invention is concerned with compounds of the formula wherein A, R 1 to R 5 and G are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions containing such compounds, to a process for their preparation and to their use for the treatment and/or prevention of diseases which are associated with the modulation of SST receptors subtype 5.

  这项发明涉及以下式的化合物 其中A，R1至R5和G如描述和声明中所定义，并其药学上可接受的盐。该发明还涉及含有这种化合物的药物组合物，以及用于制备它们的方法和它们用于治疗和/或预防与调节SST受体亚型5相关的疾病的用途。
• 一类喹唑啉衍生物、其组合物及用途
  申请人：中国科学院上海药物研究所

  公开号：CN107814792B

  公开（公告）日：2021-08-10

  本发明涉及通式I所示的喹唑啉衍生物、其组合物及它们作为PGK1抑制剂在制备抗肿瘤药物的用途和在治疗恶性肿瘤中的用途。
• Discovery of potent CCR4 antagonists: Synthesis and structure–activity relationship study of 2,4-diaminoquinazolines
  作者：Kazuhiro Yokoyama、Noriko Ishikawa、Susumu Igarashi、Noriyuki Kawano、Kazuyuki Hattori、Takahiro Miyazaki、Shin-ichi Ogino、Yuzo Matsumoto、Makoto Takeuchi、Mitsuaki Ohta

  DOI：10.1016/j.bmc.2008.05.036

  日期：2008.7

  A new series of quinazolines that function as CCR4 antagonists were discovered during the screening of our corporate compound libraries. Subsequent compound optimization elucidated the structure-activity relationships and led the identification of 2-(1,4'-bipiperidine-10-yl)-N-cycloheptyl-6,7-dimethoxyquinazolin-4- amine 14a, which showed potent inhibition in the [S-35] GTPcS-binding assay (IC50 = 18 nM). This compound also inhibited the chemotaxis of human and mouse CCR4-expressing cells ( IC50 = 140 nM, 39 nM). (c) 2008 Elsevier Ltd. All rights reserved.
• PYRIMIDINE, QUINAZOLINE, PTERIDINE AND TRIAZINE DERIVATIVES
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2001867B1

  公开（公告）日：2009-07-01