2-(2-hydroxy-3-methoxyphenyl)-5,6,7,8-tetrahydrobenzothieno[2,3-d] pyrimidin-4(3H)-one | 357618-27-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-(2-hydroxy-3-methoxyphenyl)-5,6,7,8-tetrahydrobenzothieno[2,3-d] pyrimidin-4(3H)-one
• 英文别名: 2-(2-hydroxy-3-methoxyphenyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one；2-(2-hydroxy-3-methoxyphenyl)-5,6,7,8-tetrahydro-3H-[1]benzothiolo[2,3-d]pyrimidin-4-one
• CAS: 357618-27-0
• 化学式: C₁₇H₁₆N₂O₃S
• 分子量: 328.392
• InChiKey: ZJKYMNBOQCAOEE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  99.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  环己酮 在 盐酸 、 sulfur 、 二乙胺 作用下， 以 正丁醇 为溶剂， 反应 12.0h， 生成 2-(2-hydroxy-3-methoxyphenyl)-5,6,7,8-tetrahydrobenzothieno[2,3-d] pyrimidin-4(3H)-one
  参考文献：
  名称：

  Thienopyrimidine derivatives exert their anticancer efficacy via apoptosis induction, oxidative stress and mitotic catastrophe

  摘要：

  In this study, a series of 13 structural variants of thieno[2,3d]pyrimidine derivatives (6a-6m) were synthesized and screened for cytotoxicity in a panel of colorectal, ovarian, and brain cancer cell lines. The selectivity of the compounds was assessed by determining the cytotoxicity in normal epithelial cell line (CHO). The most potent compound, 6j, was efficacious (with IC50 range of 0.6-1.2 mu M) in colon (HCT116 and HCT15), brain (LN-229 and GBM-10) and ovarian (A2780 and OV2008) cancer cell lines. In contrast, in the normal cell line (CHO), the IC50 values for 6j were 14 +/- 1.3 mu M. Compound 6j significantly inhibited the clonogenic potential of HCT116, OV2008 and A2780 cell lines in concentration dependent (0.5 - 4 mu M) manner. Also, 6j induced 1) formation of reactive oxygen species; 2) apoptosis and 3) mitotic catastrophe in HCT116 and OV2008 cells (IC50 = 0.5-2 mu M). Furthermore, apoptosis was the predominant mechanism of death in A2780 cells. The cytotoxicity of 6j in wild type HCT116 cells was similar to that in HCT116 cells lacking the apoptotic genes for Bax, Bak, or Bak and Bax, indicating that 6j induces mitotic catastrophe as alternative mechanism of death when when certain apoptotic proteins are absent. In summary, this study has identified a lead molecule, 6j, that selectively induces oxidative stress, apoptosis and mitotic catastrophe in specific cancer (colon and ovarian) cell lines. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.07.028