5-(benzo[b]thiophen-2-yl)-N-(5-(ethylsulfonyl)-2-methoxyphenyl)oxazol-2-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 5-(benzo[b]thiophen-2-yl)-N-(5-(ethylsulfonyl)-2-methoxyphenyl)oxazol-2-amine
• 英文别名: BM09915；5-(1-benzothiophen-2-yl)-N-(5-ethylsulfonyl-2-methoxyphenyl)-1,3-oxazol-2-amine
• 化学式: C₂₀H₁₈N₂O₄S₂
• 分子量: 414.506
• InChiKey: IPHOJHHAZPKUQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-乙酰基苯并噻吩 在 sodium azide 、 三苯基膦 、 copper(ll) bromide 作用下， 以 1,4-二氧六环 、 甲醇 、 氯仿 、 丙酮 为溶剂， 反应 28.5h， 生成 5-(benzo[b]thiophen-2-yl)-N-(5-(ethylsulfonyl)-2-methoxyphenyl)oxazol-2-amine
  参考文献：
  名称：

  Novel CLK1 inhibitors based on N-aryloxazol-2-amine skeleton - A possible way to dual VEGFR2 TK/CLK ligands

  摘要：

  Background: Inhibitors of CLK protein kinases suppress cell growth and induce apoptosis by modulating pre-mRNA splicing in cancer. CLK family kinases are also involved in alternative splicing and RNA processing in Duchenne muscular dystrophy, Alzheimer's disease, HIV-1, and influenza virus. Small inhibitors are valuable tools for better understanding the molecular mechanisms of splicing and may serve as seeds for a novel class of therapeutics.Achievements: Here we describe a discovery of four novel CLK1 inhibitors possessing N-aryloxazol-2amine skeleton. Their activity against CLK1 (IC50: 20, 30, 40 and 80 nM) and some other CMGC kinases, predicted CLK binding poses, synthesis and physico-chemical characteristics are also stated. Additionally analysis of all PDB available CLK structures and interactions of their ligands was performed. There are only few powerful dual CLK/VEGFR inhibitors known in the literature. We proposed that our inhibitors have similar binding places and interactions in CLK1, 3 and VEGFR2 TK mostly due to the joint N-aryloxazol-2-amine pharmacophoric fragment. One of our N-aryloxazol-2-amines already proved a good activity against both VEGFR2 and CLK1 enzymes (23/80 nM, resp). We, proposed that the presented class of compounds has a potential to be developed in dual VEGFR2/CLK clinical compounds with prospective synergy to treat cancer. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.11.003

文献信息

• Novel CLK1 inhibitors based on N-aryloxazol-2-amine skeleton - A possible way to dual VEGFR2 TK/CLK ligands
  作者：Miroslav Murár、Juraj Dobiaš、Peter Šramel、Gabriela Addová、Gilles Hanquet、Andrej Boháč

  DOI：10.1016/j.ejmech.2016.11.003

  日期：2017.1

  Background: Inhibitors of CLK protein kinases suppress cell growth and induce apoptosis by modulating pre-mRNA splicing in cancer. CLK family kinases are also involved in alternative splicing and RNA processing in Duchenne muscular dystrophy, Alzheimer's disease, HIV-1, and influenza virus. Small inhibitors are valuable tools for better understanding the molecular mechanisms of splicing and may serve as seeds for a novel class of therapeutics.Achievements: Here we describe a discovery of four novel CLK1 inhibitors possessing N-aryloxazol-2amine skeleton. Their activity against CLK1 (IC50: 20, 30, 40 and 80 nM) and some other CMGC kinases, predicted CLK binding poses, synthesis and physico-chemical characteristics are also stated. Additionally analysis of all PDB available CLK structures and interactions of their ligands was performed. There are only few powerful dual CLK/VEGFR inhibitors known in the literature. We proposed that our inhibitors have similar binding places and interactions in CLK1, 3 and VEGFR2 TK mostly due to the joint N-aryloxazol-2-amine pharmacophoric fragment. One of our N-aryloxazol-2-amines already proved a good activity against both VEGFR2 and CLK1 enzymes (23/80 nM, resp). We, proposed that the presented class of compounds has a potential to be developed in dual VEGFR2/CLK clinical compounds with prospective synergy to treat cancer. (C) 2016 Elsevier Masson SAS. All rights reserved.