2-((2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)amino)ethan-1-ol | 259101-08-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-((2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)amino)ethan-1-ol
• 英文别名: 2-[[2-Amino-5-[(phenylmethyl)thio]thiazolo[4,5-d]pyrimidin-7-yl]amino]ethanol；2-[(2-Amino-5-benzylsulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]ethanol
• CAS: 259101-08-1
• 化学式: C₁₄H₁₅N₅OS₂
• 分子量: 333.438
• InChiKey: PXHJGEFHFPDEDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  151
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-amino-5-[(phenylmethyl)thio]thiazolo[4,5-d]pyrimidin-7(4H)-one 在 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基苯胺 为溶剂， 反应 9.0h， 生成 2-((2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)amino)ethan-1-ol
  参考文献：
  名称：

  PB-10, a thiazolo[4,5-d] pyrimidine derivative, targets p21-activated kinase 4 in human colorectal cancer cells

  摘要：

  Targeting p21-activated kinase 4 (PAK4) is a potential therapeutic strategy against human colorectal cancer (CRC). In this study, we synthesized a series of novel thiazolo [4,5-d]pyrimidine derivatives (PB-1-12) and identified PB-10 (PAK4 IC50 = 15.12 mu M) as a potential and potent PAK4 inhibitor. Our results showed that PB10 significantly suppressed the proliferation and colony formation of human CRC cells. PB-10 also arrested HCT-116 CRC cells at sub G0/G1 phase while promoting the expression of proapoptotic proteins. In addition, PB-10 inhibited migration, invasion, and adhesion as well as the PAK4 downstream signaling pathway in HCT-116 cells. Molecular docking analysis showed possible binding modes between PB-10 and PAK4. Our study provides a novel compound that may block the PAK4 signaling in CRC cells.

  DOI：

  10.1016/j.bmcl.2019.126807

文献信息

• NOVEL THIAZOLOPYRIMIDINE COMPOUNDS
  申请人：AstraZeneca AB

  公开号：EP1104425B1

  公开（公告）日：2003-01-29
• US6806273B1
  申请人：——

  公开号：US6806273B1

  公开（公告）日：2004-10-19
• PB-10, a thiazolo[4,5-d] pyrimidine derivative, targets p21-activated kinase 4 in human colorectal cancer cells
  作者：Ruijuan Li、Hanxun Wang、Jian Wang、Maosheng Cheng

  DOI：10.1016/j.bmcl.2019.126807

  日期：2020.1

  Targeting p21-activated kinase 4 (PAK4) is a potential therapeutic strategy against human colorectal cancer (CRC). In this study, we synthesized a series of novel thiazolo [4,5-d]pyrimidine derivatives (PB-1-12) and identified PB-10 (PAK4 IC50 = 15.12 mu M) as a potential and potent PAK4 inhibitor. Our results showed that PB10 significantly suppressed the proliferation and colony formation of human CRC cells. PB-10 also arrested HCT-116 CRC cells at sub G0/G1 phase while promoting the expression of proapoptotic proteins. In addition, PB-10 inhibited migration, invasion, and adhesion as well as the PAK4 downstream signaling pathway in HCT-116 cells. Molecular docking analysis showed possible binding modes between PB-10 and PAK4. Our study provides a novel compound that may block the PAK4 signaling in CRC cells.