4,5-dimethyl-2-(o-tolyl)oxazole 3-oxide | 933027-20-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4,5-dimethyl-2-(o-tolyl)oxazole 3-oxide
• 英文别名: 4,5-dimethyl-2-o-tolyl-oxazole 3-oxide；Oxazole,4,5-dimethyl-2-(2-methylphenyl)-,3-oxide；4,5-dimethyl-2-(2-methylphenyl)-3-oxido-1,3-oxazol-3-ium
• CAS: 933027-20-4
• 化学式: C₁₂H₁₃NO₂
• mdl: MFCD15093746
• 分子量: 203.241
• InChiKey: TYQIQQQOKTXPNI-UHFFFAOYSA-N

物化性质

• 沸点：
  353.1±52.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  4,5-dimethyl-2-(o-tolyl)oxazole 3-oxide 在 三氯氧磷 作用下， 以 氯仿 为溶剂， 反应 12.0h， 以79%的产率得到4-(chloromethyl)-5-methyl-2-(o-tolyl)oxazole
  参考文献：
  名称：

  [EN] CHIRALE OXAZOLE-ARYLPROPIONIC ACID DERIVATIVES AND THEIR USE AS PPAR AGONISTS
  [FR] DERIVES D'ACIDE OXAZOLE-ARYLPROPIONIQUE CHIRAL ET LEUR UTILISATION EN TANT QU'AGONISTES DU RECEPTEUR PPAR

  摘要：

  本发明涉及式（I）的化合物，其中R1至R6和n如描述和索赔中所定义，并且其药学上可接受的盐和酯。这些化合物可用于治疗和/或预防由PPARα和/或PPARϜ激动剂调节的疾病，例如II型糖尿病。

  公开号：

  WO2004031162A1
• 作为产物：
  描述：

  二乙酰一肟 、 2-甲基苯甲醛 在 盐酸 作用下， 以 溶剂黄146 为溶剂， 反应 4.0h， 生成 4,5-dimethyl-2-(o-tolyl)oxazole 3-oxide
  参考文献：
  名称：

  [EN] CHIRALE OXAZOLE-ARYLPROPIONIC ACID DERIVATIVES AND THEIR USE AS PPAR AGONISTS
  [FR] DERIVES D'ACIDE OXAZOLE-ARYLPROPIONIQUE CHIRAL ET LEUR UTILISATION EN TANT QU'AGONISTES DU RECEPTEUR PPAR

  摘要：

  本发明涉及式（I）的化合物，其中R1至R6和n如描述和索赔中所定义，并且其药学上可接受的盐和酯。这些化合物可用于治疗和/或预防由PPARα和/或PPARϜ激动剂调节的疾病，例如II型糖尿病。

  公开号：

  WO2004031162A1

文献信息

• Novel oxazole derivatives
  申请人：Binggeli Alfred

  公开号：US20050267180A1

  公开（公告）日：2005-12-01

  The present invention relates to compounds of formula (I) wherein wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and n are as described herein. The compounds of the present invention can be used as medicaments for the treatment and/or prevention of diseases which are modulated by PPARα and/or PPARγ agonists. Examples of such diseases are diabetes, particularly non-insulin dependent diabetes mellitus, elevated blood pressure, increased lipid and cholesterol levels, atherosclerotic diseases, metabolic syndrome, endothelial dysfunction, procoagulant state, dyslipidemia, polycystic ovary syndrome, inflammatory diseases (such as e.g. crown disease, inflammatory bowel disease, collitis, pancreatitis, cholestasis/fibrosis of the liver, and diseases that have an inflammatory component such as e.g. Alzheimer's disease or impaired/improvable cognitive function) and proliferative diseases.

  本发明涉及式(I)化合物，其中R1、R2、R3、R4、R5、R6和n如本文所述。本发明的化合物可用作治疗和/或预防由PPARα和/或PPARγ激动剂调节的疾病的药物。此类疾病的例子包括糖尿病，特别是非胰岛素依赖性糖尿病，高血压，升高的脂质和胆固醇水平，动脉粥样硬化疾病，代谢综合征，内皮功能障碍，促凝状态，脂质代谢异常，多囊卵巢综合征，炎症性疾病（例如克隆病、炎症性肠病、结肠炎、胰腺炎、肝胆疾病/纤维化以及具有炎症成分的疾病，例如阿尔茨海默病或受损/可改善的认知功能）和增生性疾病。
• 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.
• Aleglitazar, a new, potent, and balanced dual PPARα/γ agonist for the treatment of type II diabetes
  作者：Agnes Bénardeau、Jörg Benz、Alfred Binggeli、Denise Blum、Markus Boehringer、Uwe Grether、Hans Hilpert、Bernd Kuhn、Hans Peter Märki、Markus Meyer、Kurt Püntener、Susanne Raab、Armin Ruf、Daniel Schlatter、Peter Mohr

  DOI：10.1016/j.bmcl.2009.03.036

  日期：2009.5

  Design, synthesis, and SAR of novel alpha-alkoxy-beta-arylpropionic acids as potent and balanced PPARalphagamma coagonists are described. One representative thereof, Aleglitazar ((S)-2Aa), was chosen for clinical development. Its X-ray structure in complex with both receptors as well as its high efficacy in animal models of T2D and dyslipidemia are also presented.
• 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.
• CHIRALE OXAZOLE-ARYLPROPIONIC ACID DERIVATIVES AND THEIR USE AS PPAR AGONISTS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP1551814A1

  公开（公告）日：2005-07-13