ethyl 6-(4-acrylamidophenyl)imidazo[2,1-b]thiazole-3-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 6-(4-acrylamidophenyl)imidazo[2,1-b]thiazole-3-carboxylate
• 英文别名: Ethyl 6-[4-(prop-2-enoylamino)phenyl]imidazo[2,1-b][1,3]thiazole-3-carboxylate；ethyl 6-[4-(prop-2-enoylamino)phenyl]imidazo[2,1-b][1,3]thiazole-3-carboxylate
• 化学式: C₁₇H₁₅N₃O₃S
• 分子量: 341.39
• InChiKey: HORZLCSKYDLIQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基噻唑-4-甲酸乙酯 在 tin(II) chloride dihdyrate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 ethyl 6-(4-acrylamidophenyl)imidazo[2,1-b]thiazole-3-carboxylate
  参考文献：
  名称：

  Discovery of 6-phenylimidazo[2,1-b]thiazole derivatives as a new type of FLT3 inhibitors

  摘要：

  In this investigation, a series of 6-phenylimidazo[2,1-b] thiazole derivatives were synthesized. Structure-activity relationship (SAR) analysis of these compounds based on cellular assays led to the discovery of a number of compounds that showed potent activity against FLT3-dependent human acute myeloid leukemia (AML) cell line MV4-11, but very weak or no activity against FLT3-independent human cervical cancer cell line Hela. FLT3 kinase inhibition assays were then performed on the three most active compounds. Among these compounds, 6-(4-(3-(5-(tert-butyl)isoxazol- 3-yl)ureido)phenyl)-N-(3-(dimethylamino)propyl)imidazo[2,1-b]thiazole-3-carboxamide (19) exhibited the highest potency in both cellular (MV4-11, IC50: 0.002 mu M) and enzymatic (FLT3, IC50: 0.022 mu M) assays. Further in-depth in vitro anti-AML activity and mechanism of action studies were carried out on compound 19. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.08.068

文献信息

• Discovery of 6-phenylimidazo[2,1-b]thiazole derivatives as a new type of FLT3 inhibitors
  作者：Xing-Dong Lin、Hui-Wen Yang、Shuang Ma、Wei-Wei Li、Chun-Hui Zhang、Wen-Jing Wang、Rong Xiang、Lin-Li Li、Sheng-Yong Yang

  DOI：10.1016/j.bmcl.2015.08.068

  日期：2015.10

  In this investigation, a series of 6-phenylimidazo[2,1-b] thiazole derivatives were synthesized. Structure-activity relationship (SAR) analysis of these compounds based on cellular assays led to the discovery of a number of compounds that showed potent activity against FLT3-dependent human acute myeloid leukemia (AML) cell line MV4-11, but very weak or no activity against FLT3-independent human cervical cancer cell line Hela. FLT3 kinase inhibition assays were then performed on the three most active compounds. Among these compounds, 6-(4-(3-(5-(tert-butyl)isoxazol- 3-yl)ureido)phenyl)-N-(3-(dimethylamino)propyl)imidazo[2,1-b]thiazole-3-carboxamide (19) exhibited the highest potency in both cellular (MV4-11, IC50: 0.002 mu M) and enzymatic (FLT3, IC50: 0.022 mu M) assays. Further in-depth in vitro anti-AML activity and mechanism of action studies were carried out on compound 19. (C) 2015 Elsevier Ltd. All rights reserved.