N¹-(2'-cyclopropylaminoquinazol-4'-yl)-6-methoxy-1,2,3,4-tetrahydroquinoline

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N¹-(2'-cyclopropylaminoquinazol-4'-yl)-6-methoxy-1,2,3,4-tetrahydroquinoline
• 英文别名: 2-cyclopropylamino-4-(6-methoxy-1,2,3,4-tetrahydro-1-quinolyl)quinazoline；N-cyclopropyl-4-(6-methoxy-3,4-dihydro-2H-quinolin-1-yl)quinazolin-2-amine
• 化学式: C₂₁H₂₂N₄O
• 分子量: 346.432
• InChiKey: BQVHGVQPQZFDCZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  50.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,4-二氯喹唑啉 在 碳酸氢钠 作用下， 以 乙醇 、 正己醇 为溶剂， 反应 3.25h， 生成 N¹-(2'-cyclopropylaminoquinazol-4'-yl)-6-methoxy-1,2,3,4-tetrahydroquinoline
  参考文献：
  名称：

  N-Aryl Unsaturated Fused Ring Tertiary Amine Compounds, Preparation Method and Anti-Tumor Applications Thereof

  摘要：

  本发明涉及公式I的化合物或其药学上可接受的盐，其制备方法，包含该化合物的药物组合物，以及其在制造用于治疗疾病或障碍的药物中的应用，其中R1、R2、R5、R6、X、Y、Q、W、n1和n2的定义如描述中所述。

  公开号：

  US20150141407A1

文献信息

• N-Aryl Unsaturated Fused Ring Tertiary Amine Compounds, Preparation Method and Anti-Tumor Applications Thereof
  申请人：Institute of Pharmacology and Toxicology Academy of Military Medical Sciences P.L.A. China

  公开号：US20150141407A1

  公开（公告）日：2015-05-21

  The present invention relates to a compound of Formula I or a pharmaceutically acceptable salt thereof, its preparation method, a pharmaceutical composition comprising the compound, and its use in manufacture of a medicament for treatment of a disease or disorder, wherein R 1 , R 2 , R 5 , R 6 , X, Y, Q, W, n 1 and n 2 are defined as those stated in the description.

  本发明涉及公式I的化合物或其药学上可接受的盐，其制备方法，包含该化合物的药物组合物，以及其在制造用于治疗疾病或障碍的药物中的应用，其中R1、R2、R5、R6、X、Y、Q、W、n1和n2的定义如描述中所述。
• N-ARYL UNSATURATED FUSED RING TERTIARY AMINE COMPOUND, PREPARATION METHOD THEREOF AND ANTITUMOR APPLICATION THEREOF
  申请人：Institute of Pharmacology and Toxicology Academy of Military Medical Sciences P.L.A. China

  公开号：EP2857393B1

  公开（公告）日：2018-09-12
• US9751884B2
  申请人：——

  公开号：US9751884B2

  公开（公告）日：2017-09-05
• Optimization of N-aryl-6-methoxy-1,2,3,4-tetrahydroquinolines as tubulin polymerization inhibitors
  作者：Sheng-Biao Wang、Xiao-Feng Wang、Bingjie Qin、Emika Ohkoshi、Kan-Yen Hsieh、Ernest Hamel、Mu-Tian Cui、Dong-Qing Zhu、Masuo Goto、Susan L. Morris-Natschke、Kuo-Hsiung Lee、Lan Xie

  DOI：10.1016/j.bmc.2015.07.016

  日期：2015.9

  Thirteen new N-aryl 1,2,3,4-tetrahydroquinoline compounds (4a-f, 6a-c, and 8a-d) were synthesized and evaluated for antitumor activity and drug-like properties. Compound 4a exhibited high inhibitory potency with low nanomolar GI(50) values of 16-20 nM in cellular assays, including excellent activity against the P-glycoprotein overexpressing cell line KBvin. Compound 4a inhibited colchicine binding to tubulin and tubulin assembly with an IC50 value of 0.85 mu M, superior to the reference compound CA4 (1.2 mu M) in the same assay. In addition, 4a also exhibited highly improved water solubility (75 mu g/mL) and a suitable log P value (3.43) at pH 7.4. With a good balance between antitumor potency and drug-like properties, compound 4a could be a new potential drug candidate for further development. Current results on SAR studies and molecular modeling provided more insight about this class of compounds as tubulin polymerization inhibitors targeting the colchicine site. (C) 2015 Elsevier Ltd. All rights reserved.