6-(dimethoxymethyl)-2-(methylthio)pyrimidin-4-ol | 21326-25-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 6-(dimethoxymethyl)-2-(methylthio)pyrimidin-4-ol
• 英文别名: 6-(Dimethoxymethyl)-2-(methylthio)-4(3H)-pyrimidinone；4-(dimethoxymethyl)-2-methylsulfanyl-1H-pyrimidin-6-one
• CAS: 21326-25-0
• 化学式: C₈H₁₂N₂O₃S
• 分子量: 216.261
• InChiKey: VPRQZLQIQHFCHO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  85.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(dimethoxymethyl)-2-(methylthio)pyrimidin-4-ol 在 ammonium hydroxide 、 1,5,7-三氮杂双环[4.4.0]癸-5-烯 、 镍 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 6-[5-(4-Fluorophenyl)-3-(3-morpholin-4-ylpropyl)imidazol-4-yl]pyrimidin-4-amine
  参考文献：
  名称：

  Pyrimidinylimidazole inhibitors of CSBP/P38 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes

  摘要：

  Pyrimidine analogs of the pyridinylimidazole class of CSBP/p38 kinase inhibitors were prepared in an effort to reduce the potent inhibition of hepatic cytochrome P450 observed for the pyridinyl compounds. The substitution of pyrimidin-4-yl, 2-methoxypyrimidin-4-yl, or 2-methylaminopyrimidin-4-yl for pyridin-4-yl effectively dissociates CSBP/p38 kinctse from P450 inhibition for this series and furthermore achieves an increase in oral activity. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00549-6
• 作为产物：
  描述：

  4,4-二甲氧基乙酰乙酸甲酯 、 S-甲基异硫脲硫酸盐 在 potassium carbonate 作用下， 以 水 为溶剂， 以92%的产率得到6-(dimethoxymethyl)-2-(methylthio)pyrimidin-4-ol
  参考文献：
  名称：

  [EN] HETEROARYL COMPOUNDS AS CXCR4 INHIBITORS, COMPOSITION AND METHOD USING THE SAME
  [FR] COMPOSÉS HÉTÉROARYLÉS UTILISÉS COMME INHIBITEURS DE CXCR4, COMPOSITION ET PROCÉDÉ D'UTILISATION DE CEUX-CI

  摘要：

  本公开提供了Formula (I)的杂环芳基化合物，其制备方法，含有它们的药物组合物，以及它们在治疗源自或与CXCR4途径相关的疾病和障碍中的应用。

  公开号：

  WO2019060860A1

文献信息

• Design, synthesis, and evaluation of novel CXCR4 antagonists based on an aminoquinoline template
  作者：Yu Lin、Zhanhui Li、Chen Xu、Kaijiang Xia、Shuwei Wu、Yongjin Hao、Qing Yang、Haikuo Ma、Jiyue Zheng、Lusong Luo、Fang Zhu、Sudan He、Xiaohu Zhang

  DOI：10.1016/j.bioorg.2020.103824

  日期：2020.6

  cancer metastasis. Here we report the structure-activity relationship study of novel CXCR4 antagonists based on an aminoquinoline template. This template is devoid of the chiral center in the classical tetrahydroquinoline (THQ) ring moiety and therefore can be easily synthesized. A number of potent CXCR4 antagonists were identified, exemplified by compound 3, which demonstrated excellent binding affinity

  由于趋化因子受体CXCR4参与了诸如HIV感染和癌症转移等病理状况，因此已被研究为药物靶标。在这里，我们报告基于氨基喹啉模板的新型CXCR4拮抗剂的构效关系研究。该模板在经典的四氢喹啉（THQ）环部分中没有手性中心，因此可以轻松合成。鉴定了许多有效的CXCR4拮抗剂，以化合物3为例，它们表现出与CXCR4受体的优异结合亲和力（IC50 = 57 nM），并抑制了CXCL12诱导的胞质钙增加（IC50 = 0.24 nM）。此外，化合物3在transwell入侵试验中有效抑制了CXLC12 / CXCR4介导的细胞迁移。简化的合成方法结合良好的理化性质（例如
• [EN] HETEROARYL COMPOUNDS AS CXCR4 INHIBITORS, COMPOSITION AND METHOD USING THE SAME<br/>[FR] COMPOSÉS HÉTÉROARYLÉS UTILISÉS COMME INHIBITEURS DE CXCR4, COMPOSITION ET PROCÉDÉ D'UTILISATION DE CEUX-CI
  申请人：SUZHOU YUNXUAN YIYAO KEJI YOUXIAN GONGSI

  公开号：WO2019060860A1

  公开（公告）日：2019-03-28

  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.

  本公开提供了Formula (I)的杂环芳基化合物，其制备方法，含有它们的药物组合物，以及它们在治疗源自或与CXCR4途径相关的疾病和障碍中的应用。
• HETEROARYL COMPOUNDS AS CXCR4 INHIBITORS, COMPOSITION AND METHOD USING THE SAME
  申请人：CGeneTech (Suzhou, China) Co., Ltd.

  公开号：EP3687540A1

  公开（公告）日：2020-08-05
• 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.
• Pyrimidinylimidazole inhibitors of CSBP/P38 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes
  作者：Jerry L. Adams、Jeffrey C. Boehm、Shouki Kassis、Peter D. Gorycki、Edward F. Webb、Ralph Hall、Margaret Sorenson、John C. Lee、Andrew Ayrton、Don E. Griswold、Timothy F. Gallagher

  DOI：10.1016/s0960-894x(98)00549-6

  日期：1998.11

  Pyrimidine analogs of the pyridinylimidazole class of CSBP/p38 kinase inhibitors were prepared in an effort to reduce the potent inhibition of hepatic cytochrome P450 observed for the pyridinyl compounds. The substitution of pyrimidin-4-yl, 2-methoxypyrimidin-4-yl, or 2-methylaminopyrimidin-4-yl for pyridin-4-yl effectively dissociates CSBP/p38 kinctse from P450 inhibition for this series and furthermore achieves an increase in oral activity. (C) 1998 Elsevier Science Ltd. All rights reserved.