2-(3-chlorophenyl)-4,5-dimethyloxazole 3-oxide | 933027-35-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(3-chlorophenyl)-4,5-dimethyloxazole 3-oxide
• 英文别名: 2-(3-chlorophenyl)-4,5-dimethyl-3-oxido-1,3-oxazol-3-ium
• CAS: 933027-35-1
• 化学式: C₁₁H₁₀ClNO₂
• mdl: MFCD15093780
• 分子量: 223.659
• InChiKey: UJUXYRRHXSUHPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  38.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(3-chlorophenyl)-4,5-dimethyloxazole 3-oxide 在 potassium hydroxide 、 三氯氧磷 作用下， 以 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 16.5h， 生成 1-((2-(3-chlorolphenyl)-5-methyloxazol-4-yl)methyl)piperidine-4-carboxylic acid
  参考文献：
  名称：

  Development of an Aryloxazole Class of Hepatitis C Virus Inhibitors Targeting the Entry Stage of the Viral Replication Cycle

  摘要：

  Reliance on hepatitis C virus (HCV) replicon systems and protein-based screening assays has led to treatments that target HCV viral replication proteins. The model does not encompass other viral replication cycle steps such as entry, processing, assembly and secretion, or viral host factors. We previously applied a phenotypic high-throughput screening platform based on an infectious HCV system and discovered an aryloxazole-based anti-HCV hit. Structure-activity relationship studies revealed several compounds exhibiting EC50 values below 100 nM. Lead compounds showed inhibition of the HCV pseudoparticle entry, suggesting a different mode of action from existing HCV drugs. Hit 7a and lead 7ii both showed synergistic effects in combination with existing HCV drugs. In vivo pharmacokinetics studies of Iii showed high liver distribution and long half-life without obvious hepatotoxicity. The lead compounds are promising as preclinical candidates for the treatment of HCV infection and as molecular probes to study HCV pathogenesis.

  DOI：

  10.1021/acs.jmedchem.7b00561
• 作为产物：
  描述：

  3-氯苯甲醛 、 二乙酰一肟 在 盐酸 作用下， 以 1,4-二氧六环 、 溶剂黄146 为溶剂， 反应 16.0h， 以81%的产率得到2-(3-chlorophenyl)-4,5-dimethyloxazole 3-oxide
  参考文献：
  名称：

  Development of an Aryloxazole Class of Hepatitis C Virus Inhibitors Targeting the Entry Stage of the Viral Replication Cycle

  摘要：

  Reliance on hepatitis C virus (HCV) replicon systems and protein-based screening assays has led to treatments that target HCV viral replication proteins. The model does not encompass other viral replication cycle steps such as entry, processing, assembly and secretion, or viral host factors. We previously applied a phenotypic high-throughput screening platform based on an infectious HCV system and discovered an aryloxazole-based anti-HCV hit. Structure-activity relationship studies revealed several compounds exhibiting EC50 values below 100 nM. Lead compounds showed inhibition of the HCV pseudoparticle entry, suggesting a different mode of action from existing HCV drugs. Hit 7a and lead 7ii both showed synergistic effects in combination with existing HCV drugs. In vivo pharmacokinetics studies of Iii showed high liver distribution and long half-life without obvious hepatotoxicity. The lead compounds are promising as preclinical candidates for the treatment of HCV infection and as molecular probes to study HCV pathogenesis.

  DOI：

  10.1021/acs.jmedchem.7b00561

文献信息

• Structure-based design of indole propionic acids as novel PPARα/γ co-agonists
  作者：Bernd Kuhn、Hans Hilpert、Jörg Benz、Alfred Binggeli、Uwe Grether、Roland Humm、Hans Peter Märki、Markus Meyer、Peter Mohr

  DOI：10.1016/j.bmcl.2006.05.007

  日期：2006.8

  In the quest for novel PPARalpha/gamma co-agonists as putative drugs for the treatment of type 2 diabetes and dyslipidemia, we have used a structure-based design approach to identify propionic acids with a 1,5-disubstituted indole scaffold as potent PPARalpha/gamma activators. Compounds 13, 24, and 28 are examples of submicromolar dual agonists with different alpha/gamma EC50 ratios that are selective against the delta-isoform. Analysis of the X-ray complex structure of PPARgamma with the indole propionic acid 13 provides a rationalization for some of the observed SAR.
• Development of an Aryloxazole Class of Hepatitis C Virus Inhibitors Targeting the Entry Stage of the Viral Replication Cycle
  作者：Shanshan He、Kelin Li、Billy Lin、Zongyi Hu、Jingbo Xiao、Xin Hu、Amy Q. Wang、Xin Xu、Marc Ferrer、Noel Southall、Wei Zheng、Jeffrey Aubé、Frank J. Schoenen、Juan J. Marugan、T. Jake Liang、Kevin J. Frankowski

  DOI：10.1021/acs.jmedchem.7b00561

  日期：2017.7.27

  Reliance on hepatitis C virus (HCV) replicon systems and protein-based screening assays has led to treatments that target HCV viral replication proteins. The model does not encompass other viral replication cycle steps such as entry, processing, assembly and secretion, or viral host factors. We previously applied a phenotypic high-throughput screening platform based on an infectious HCV system and discovered an aryloxazole-based anti-HCV hit. Structure-activity relationship studies revealed several compounds exhibiting EC50 values below 100 nM. Lead compounds showed inhibition of the HCV pseudoparticle entry, suggesting a different mode of action from existing HCV drugs. Hit 7a and lead 7ii both showed synergistic effects in combination with existing HCV drugs. In vivo pharmacokinetics studies of Iii showed high liver distribution and long half-life without obvious hepatotoxicity. The lead compounds are promising as preclinical candidates for the treatment of HCV infection and as molecular probes to study HCV pathogenesis.