N-(2-(5-(4-(hydroxymethyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)ethyl)methanesulfonamide | 1450604-07-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(2-(5-(4-(hydroxymethyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)ethyl)methanesulfonamide
• CAS: 1450604-07-5
• 化学式: C₁₇H₂₄N₂O₅S₂
• 分子量: 400.52
• InChiKey: XMNFBVBMKNGXMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.19
• 重原子数：
  26.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  97.75
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  N-(2-(5-(4-(hydroxymethyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)ethyl)methanesulfonamide 在 1,1,1,3,3,3-六溴丙酮 、 三苯基膦 、 sodium hydroxide 作用下， 以 乙醇 、 乙腈 为溶剂， 生成 N-(2-(5-(4-(((4,6-diaminopyrimidin-2-yl)thio)methyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)ethyl)methanesulfonamide
  参考文献：
  名称：

  Development of New Deoxycytidine Kinase Inhibitors and Noninvasive in Vivo Evaluation Using Positron Emission Tomography

  摘要：

  Combined inhibition of ribonucleotide reductase and deoxycytidine kinase (dCK) in multiple cancer cell lines depletes deoxycytidine triphosphate pools leading to DNA replication stress, cell cycle arrest, and apoptosis. Evidence implicating dCK in cancer cell proliferation and survival stimulated our interest in developing small molecule dCK inhibitors. Following a high throughput screen of a diverse chemical library, a structure activity relationship study was carried out Positron Emission Tomography (PET) using F-18-L-1-(2'-deoxy-2':-FluoroArabinofuranosyl) Cytosine (F-18-L-FAC), a dCK-specific substrate, was used to rapidly rank lead compounds based on their ability to inhibit dCK activity in vivo. Evaluation of a subset of the most potent compounds in cell culture (IC50 = similar to 1-12 nM) using the F-18-L-FAC PET pharmacodynatnic assay identified compounds demonstrating superior in vivo efficacy.

  DOI：

  10.1021/jm400457y
• 作为产物：
  描述：

  ethyl 2-(4-methoxy-3-(2-(methylsulfonamido)ethoxy)phenyl)-5-propylthiazole-4-carboxylate 在 二异丁基氢化铝 作用下， 以 二氯甲烷 为溶剂， 以90%的产率得到N-(2-(5-(4-(hydroxymethyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)ethyl)methanesulfonamide
  参考文献：
  名称：

  Development of New Deoxycytidine Kinase Inhibitors and Noninvasive in Vivo Evaluation Using Positron Emission Tomography

  摘要：

  Combined inhibition of ribonucleotide reductase and deoxycytidine kinase (dCK) in multiple cancer cell lines depletes deoxycytidine triphosphate pools leading to DNA replication stress, cell cycle arrest, and apoptosis. Evidence implicating dCK in cancer cell proliferation and survival stimulated our interest in developing small molecule dCK inhibitors. Following a high throughput screen of a diverse chemical library, a structure activity relationship study was carried out Positron Emission Tomography (PET) using F-18-L-1-(2'-deoxy-2':-FluoroArabinofuranosyl) Cytosine (F-18-L-FAC), a dCK-specific substrate, was used to rapidly rank lead compounds based on their ability to inhibit dCK activity in vivo. Evaluation of a subset of the most potent compounds in cell culture (IC50 = similar to 1-12 nM) using the F-18-L-FAC PET pharmacodynatnic assay identified compounds demonstrating superior in vivo efficacy.

  DOI：

  10.1021/jm400457y