N-(2-(4-(6-(3-hydroxyphenyl)imidazo[2,1-b]thiazol-5-yl)pyrimidin-2-ylamino)ethyl)-3-(trifluoromethyl)-5-morpholinobenzamide | 1350454-99-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: N-(2-(4-(6-(3-hydroxyphenyl)imidazo[2,1-b]thiazol-5-yl)pyrimidin-2-ylamino)ethyl)-3-(trifluoromethyl)-5-morpholinobenzamide
• 英文别名: N-[2-[[4-[6-(3-hydroxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]pyrimidin-2-yl]amino]ethyl]-3-morpholin-4-yl-5-(trifluoromethyl)benzamide
• CAS: 1350454-99-7
• 化学式: C₂₉H₂₆F₃N₇O₃S
• 分子量: 609.632
• InChiKey: RSHAEAWDOBIEPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  43
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  145
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2-溴-3‘-甲氧基苯乙酮 在 Oxone 、 palladium diacetate 、 三溴化硼 、 caesium carbonate 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.5h， 生成 N-(2-(4-(6-(3-hydroxyphenyl)imidazo[2,1-b]thiazol-5-yl)pyrimidin-2-ylamino)ethyl)-3-(trifluoromethyl)-5-morpholinobenzamide
  参考文献：
  名称：

  New imidazo[2,1-b]thiazole derivatives: Synthesis, in vitro anticancer evaluation, and in silico studies

  摘要：

  A series of 18 new imidazo[2,1-b]thiazole derivatives was synthesized. Their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-60 cell line panel were tested. Compounds 15, 16, 18, 22, 26-28, and 31 showed superior potency against A375P to sorafenib. In addition, compounds 26 and 27 showed selectivity toward melanoma cell lines than for other cancer types. Both compounds exerted sub-micromolar IC50 values over 7 (including A375P) and 6 melanoma cell lines, respectively. in silico studies are also reported. ADME profiling, in silico toxicity, drug-likeness, and drug-score data of compounds 26 and 27 are promising. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.08.024

文献信息

• Imidazothiazole-based potent inhibitors of V600E-B-RAF kinase with promising anti-melanoma activity: biological and computational studies
  作者：Hanan S. Anbar、Mohammed I. El-Gamal、Hamadeh Tarazi、Bong S. Lee、Hong R. Jeon、Dow Kwon、Chang-Hyun Oh

  DOI：10.1080/14756366.2020.1819260

  日期：2020.1.1

  A series of imidazothiazole derivatives possessing potential activity against melanoma cells were investigated for molecular mechanism of action. The target compounds were tested against V600E-B-RAF and RAF1 kinases. Compound1zbis the most potent against both kinases with IC(50)values 0.978 and 8.2 nM, respectively. It showed relative selectivity against V600E mutant B-RAF kinase. Compound1zbwas also tested against four melanoma cell lines and exerted superior potency (IC(50)0.18-0.59 mu M) compared to the reference standard drug, sorafenib (IC(50)1.95-5.45 mu M). Compound1zbdemonstrated also prominent selectivity towards melanoma cells than normal skin cells. It was further tested in whole-cell kinase assay and showed in-cell V600E-B-RAF kinase inhibition with IC(50)of 0.19 mu M. Compound1zbinduces apoptosis not necrosis in the most sensitive melanoma cell line, UACC-62. Furthermore, molecular dynamic and 3D-QSAR studies were done to investigate the binding mode and understand the pharmacophoric features of this series of compounds.