2-(((2-(3-fluorophenyl)-5-propylthiazol-4-yl)methyl)thio)pyrimidine-4,6-diamine | 1398232-44-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(((2-(3-fluorophenyl)-5-propylthiazol-4-yl)methyl)thio)pyrimidine-4,6-diamine
• 英文别名: 2-[[2-(3-Fluorophenyl)-5-propyl-1,3-thiazol-4-yl]methylsulfanyl]pyrimidine-4,6-diamine
• CAS: 1398232-44-4
• 化学式: C₁₇H₁₈FN₅S₂
• 分子量: 375.494
• InChiKey: NAYQDORSLYPJGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  144
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-氟苯腈 在 吡啶 、 diammonium sulfide 、 1,1,1,3,3,3-六溴丙酮 、 二异丁基氢化铝 、 三乙胺 、 三苯基膦 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 25.67h， 生成 2-(((2-(3-fluorophenyl)-5-propylthiazol-4-yl)methyl)thio)pyrimidine-4,6-diamine
  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

文献信息

• [EN] DEOXYCYTIDINE KINASE BINDING COMPOUNDS<br/>[FR] COMPOSÉS DE LIAISON À LA DÉSOXYCYTIDINE KINASE
  申请人：UNIV CALIFORNIA

  公开号：WO2012122368A1

  公开（公告）日：2012-09-13

  The invention provides compounds that bind to deoxycytidine kinase (dCK) and compositions including pharmaceutically acceptable compositions containing the compounds. The compounds are useful in treating diseases and disorders where dCK activity is implicated such as cancer and immune disorders. The compounds also find use in clinical methodologies including positron emission tomography (PET) imaging.

  本发明提供了与脱氧胞苷激酶（dCK）结合的化合物以及包含药学上可接受的组合物，其中含有这些化合物。这些化合物在治疗涉及dCK活性的疾病和障碍，如癌症和免疫障碍方面具有用途。这些化合物还适用于包括正电子发射断层扫描（PET）成像在内的临床方法。
• US9688673B2
  申请人：——

  公开号：US9688673B2

  公开（公告）日：2017-06-27