(S)-N-methyl-N-((2-methyl-6-((3-morpholinopropyl)amino)pyrimidin-4-yl)methyl)-5,6,7,8-tetrahydroquinolin-8-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (S)-N-methyl-N-((2-methyl-6-((3-morpholinopropyl)amino)pyrimidin-4-yl)methyl)-5,6,7,8-tetrahydroquinolin-8-amine
• 英文别名: (8S)-N-methyl-N-[[2-methyl-6-(3-morpholin-4-ylpropylamino)pyrimidin-4-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine
• 化学式: C₂₃H₃₄N₆O
• 分子量: 410.563
• InChiKey: BKIKXFUYXLJCAG-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  66.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  6-(氯甲基)-2-甲基嘧啶-4-醇 在 三乙胺 、 N,N-二异丙基乙胺 、 potassium iodide 、 三氯氧磷 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 2.0h， 生成 (S)-N-methyl-N-((2-methyl-6-((3-morpholinopropyl)amino)pyrimidin-4-yl)methyl)-5,6,7,8-tetrahydroquinolin-8-amine
  参考文献：
  名称：

  Structural optimization of aminopyrimidine-based CXCR4 antagonists

  摘要：

  Structural optimization of aminopyrimidine-based CXCR4 antagonists is reported. The optimization is guided by molecular docking studies based on available CXCR4-small molecule crystal complex. The optimization identifies a number of compounds with improved receptor binding affinity and functional activity exemplified by compound 23 (inhibition of APC-conjugate clone 12G5 for CXCR4 binding in a cell based assay: IC50 = 8.8 nM; inhibition of CXCL12 induced cytosolic calcium increase: IC50 = 0.02 nM). In addition, compound 23 potently inhibits CXCR4/CXLC12 mediated chemotaxis in a matrigel invasion assay. Furthermore, compound 23 exhibits good physicochemical properties (MW 367, clogP 2.1, PSA 48, pKa 7.2) and in vitro safety profiles (marginal/moderate inhibition of CYP isozymes and hERG). These results represent significant improvement over the initial hit from scaffold hybridization and suggest that compound 23 can be used as a starting point to support lead optimization. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111914

文献信息

• HETEROARYL COMPOUNDS AS CXCR4 INHIBITORS, COMPOSITION AND METHOD USING THE SAME
  申请人：Zhang Xiaohu

  公开号：US20200239439A1

  公开（公告）日：2020-07-30

  The present disclosure provides heteroaryl compounds of Formula (I), processes for their preparation, pharmaceutical compositions containing them, and their use in the treatment of diseases and disorders, arising from or related to the CXCR4 pathway.
• Structural optimization of aminopyrimidine-based CXCR4 antagonists
  作者：Fang Zhu、Yujie Wang、Qian Du、Wenxiang Ge、Zhanhui Li、Xu Wang、Chunyan Fu、Lusong Luo、Sheng Tian、Haikuo Ma、Jiyue Zheng、Yi Zhang、Xiaotian Sun、Sudan He、Xiaohu Zhang

  DOI：10.1016/j.ejmech.2019.111914

  日期：2020.2

  Structural optimization of aminopyrimidine-based CXCR4 antagonists is reported. The optimization is guided by molecular docking studies based on available CXCR4-small molecule crystal complex. The optimization identifies a number of compounds with improved receptor binding affinity and functional activity exemplified by compound 23 (inhibition of APC-conjugate clone 12G5 for CXCR4 binding in a cell based assay: IC50 = 8.8 nM; inhibition of CXCL12 induced cytosolic calcium increase: IC50 = 0.02 nM). In addition, compound 23 potently inhibits CXCR4/CXLC12 mediated chemotaxis in a matrigel invasion assay. Furthermore, compound 23 exhibits good physicochemical properties (MW 367, clogP 2.1, PSA 48, pKa 7.2) and in vitro safety profiles (marginal/moderate inhibition of CYP isozymes and hERG). These results represent significant improvement over the initial hit from scaffold hybridization and suggest that compound 23 can be used as a starting point to support lead optimization. (C) 2019 Elsevier Masson SAS. All rights reserved.