4-(ethylsulfonyl)-2-isothiocyanato-1-methoxybenzene | 681004-53-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(ethylsulfonyl)-2-isothiocyanato-1-methoxybenzene
• 英文别名: 4-Ethanesulfonyl-2-isothiocyanato-1-methoxy-benzene；Ethyl 3-isothiocyanato-4-methoxyphenyl sulfone；4-ethylsulfonyl-2-isothiocyanato-1-methoxybenzene
• CAS: 681004-53-5
• 化学式: C₁₀H₁₁NO₃S₂
• 分子量: 257.334
• InChiKey: FJLYGPAKGYDWCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  96.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(ethylsulfonyl)-2-isothiocyanato-1-methoxybenzene 在 四(三苯基膦)钯 、 四丁基氯化铵 、 三苯基膦 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 2-Anilino-5-aryloxazole 38
  参考文献：
  名称：

  Discovery and Evaluation of 2-Anilino-5-aryloxazoles as a Novel Class of VEGFR2 Kinase Inhibitors

  摘要：

  A series of derivatives of 2-anilino-5-phenyloxazole (5) has been identified as inhibitors of VEGFR2 kinase. Herein we describe the structure-activity relationship (SAR) of this novel template. Optimization of both aryl rings led to very potent inhibitors at both the enzymatic and cellular levels. Oxazole 39 had excellent solubility and good oral PK when dosed as the bis-mesylate salt and demonstrated moderate in vivo efficacy against HT29 human colon tumor xenografts. X-ray crystallography confirmed the proposed binding mode, and comparison of oxazoles 39 and 46 revealed interesting differences in orientation of 2-pyridyl and 3-pyridyl rings, respectively, attached at the meta position of the 5-phenyl ring.

  DOI：

  10.1021/jm049538w
• 作为产物：
  描述：

  硫光气 、 [5-(乙基磺酰基)-2-甲氧基苯基]胺 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 以72%的产率得到4-(ethylsulfonyl)-2-isothiocyanato-1-methoxybenzene
  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

• BISTHIAZOLE INHIBITORS OF PRO-MATRIX METALLOPROTEINASE ACTIVATION
  申请人：JACKSON Paul Francis

  公开号：US20120129842A1

  公开（公告）日：2012-05-24

  This invention relates to bisthiazole I and its therapeutic and prophylactic uses, wherein the variables A, R 5 , R 6 , and R 7 are defined in the specification. Disorders treated and/or prevented include rheumatoid arthritis.

  本发明涉及双噻唑I及其治疗和预防用途，其中变量A，R 5 ，R 6 ，和R 7 在说明书中定义。治疗的和/或预防的疾病包括类风湿性关节炎。
• PYRIDYL-THIAZOLYL INHIBITORS OF PRO-MATRIX METALLOPROTEINASE ACTIVATION
  申请人：ZHANG Yan

  公开号：US20120129843A1

  公开（公告）日：2012-05-24

  This invention relates to thiazole I and its therapeutic and prophylactic uses, wherein the variables R z , Q, J, R 1 , R 3 , R 5 , and R 6 are defined in the specification. Disorders treated and/or prevented include rheumatoid arthritis.

  这项发明涉及噻唑I及其治疗和预防用途，其中变量Rz、Q、J、R1、R3、R5和R6在规范中有定义。治疗和/或预防的疾病包括类风湿关节炎。
• TRICYCLIC INHIBITORS OF PRO-MATRIX METALLOPROTEINASE ACTIVATION
  申请人：WANG Aihua

  公开号：US20120129811A1

  公开（公告）日：2012-05-24

  This invention relates to tricycle I and its therapeutic and prophylactic uses, wherein the variables C 1 , C 2 , Z 1 , Z 2 , Q, J, R 1 , and R 3 are defined in the specification. Disorders treated and/or prevented include rheumatoid arthritis.

  本发明涉及三轮车I及其治疗和预防用途，其中变量C1、C2、Z1、Z2、Q、J、R1和R3在规范中定义。治疗和/或预防的疾病包括类风湿性关节炎。
• Quinoides and VEGFR2 TKIs influence the fate of hepatocellular carcinoma and its cancer stem cells
  作者：Deniz Cansen Kahraman、Gilles Hanquet、Loïc Jeanmart、Steve Lanners、Peter Šramel、Andrej Boháč、Rengul Cetin-Atalay

  DOI：10.1039/c6md00392c

  日期：——

  Bioactivities of quinoides 1–5 and VEGFR2 TKIs 6–10 in hepatocellular cancer (HCC) and cancer stem cells (HCSCs) were studied. Quinoide 3 was able to eradicate cancer stem cells.

  醌类化合物1-5和VEGFR2 TKIs 6-10在肝细胞癌（HCC）和癌干细胞（HCSCs）中的生物活性进行了研究。醌类化合物3能够根除癌干细胞。
• Chemical compounds
  申请人：Brown Lee Matthew

  公开号：US20050288515A1

  公开（公告）日：2005-12-29

  Oxazole derivatives, which are useful as VEGFR2, CDK2, and CDK4 inhibitors are described herein. The described invention also includes methods of making such oxazole derivatives as well as methods of using the same in the treatment of hyperproliferative diseases.

  本文介绍了一种作为VEGFR2、CDK2和CDK4抑制剂有用的噁唑衍生物。所述发明还包括制备此类噁唑衍生物的方法以及在治疗增生性疾病中使用它们的方法。