1-(5-(4-(((4,6-diaminopyrimidin-2-yl)thio)methyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)propan-2-ol | 1450603-99-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(5-(4-(((4,6-diaminopyrimidin-2-yl)thio)methyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)propan-2-ol
• 英文别名: 1-[5-[4-[(4,6-Diaminopyrimidin-2-yl)sulfanylmethyl]-5-propyl-1,3-thiazol-2-yl]-2-methoxyphenoxy]propan-2-ol；1-[5-[4-[(4,6-diaminopyrimidin-2-yl)sulfanylmethyl]-5-propyl-1,3-thiazol-2-yl]-2-methoxyphenoxy]propan-2-ol
• CAS: 1450603-99-2
• 化学式: C₂₁H₂₇N₅O₃S₂
• 分子量: 461.609
• InChiKey: CPOIYKQLEDMXOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  183
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  在 1,1,1,3,3,3-六溴丙酮 、 二异丁基氢化铝 、 三苯基膦 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 5.17h， 生成 1-(5-(4-(((4,6-diaminopyrimidin-2-yl)thio)methyl)-5-propylthiazol-2-yl)-2-methoxyphenoxy)propan-2-ol
  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

• DEOXYCYTIDINE KINASE INHIBITORS
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20170204090A1

  公开（公告）日：2017-07-20

  Provided herein are compounds that bind to dCK and methods for treating cancer.
• US9598404B2
  申请人：——

  公开号：US9598404B2

  公开（公告）日：2017-03-21
• US9981961B2
  申请人：——

  公开号：US9981961B2

  公开（公告）日：2018-05-29
• Development of New Deoxycytidine Kinase Inhibitors and Noninvasive in Vivo Evaluation Using Positron Emission Tomography
  作者：Jennifer M. Murphy、Amanda L. Armijo、Julian Nomme、Chi Hang Lee、Quentin A. Smith、Zheng Li、Dean O. Campbell、Hsiang-I Liao、David A. Nathanson、Wayne R. Austin、Jason T. Lee、Ryan Darvish、Liu Wei、Jue Wang、Ying Su、Robert Damoiseaux、Saman Sadeghi、Michael E. Phelps、Harvey R. Herschman、Johannes Czernin、Anastassia N. Alexandrova、Michael E. Jung、Arnon Lavie、Caius G. Radu

  DOI：10.1021/jm400457y

  日期：2013.9.12

  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.