6-(dimethoxymethyl)-2-(trifluoromethyl)pyrimidin-4-ol | 2924-79-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-(dimethoxymethyl)-2-(trifluoromethyl)pyrimidin-4-ol
• 英文别名: 4-Hydroxy-2-trifluormethyl-6-dimethoxymethyl-pyrimidin；6-dimethoxymethyl-2-trifluoromethyl-3H-pyrimidin-4-one；4-Hydroxy-6-dimethoxymethyl-2-(trifluoromethyl)pyrimidine；4-(dimethoxymethyl)-2-(trifluoromethyl)-1H-pyrimidin-6-one
• CAS: 2924-79-0
• 化学式: C₈H₉F₃N₂O₃
• 分子量: 238.166
• InChiKey: ZRXSNSIVVTXLFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  59.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-(dimethoxymethyl)-2-(trifluoromethyl)pyrimidin-4-ol 在 硫酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 溶剂黄146 、 三乙胺 作用下， 以 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 0.17h， 生成 (S)-N-methyl-N-((6-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)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
• 作为产物：
  描述：

  4,4-二甲氧基乙酰乙酸甲酯 、 三氟乙脒 在 potassium carbonate 、 溶剂黄146 作用下， 以 水 为溶剂， 以36%的产率得到6-(dimethoxymethyl)-2-(trifluoromethyl)pyrimidin-4-ol
  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

• 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.