diethyl 2-(4-phenylphenoxy)malonate | 97080-73-4

• 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: diethyl 2-(4-phenylphenoxy)malonate
• 英文别名: diethyl 2-[(1,1'-biphenyl)-4-yloxy]malonate；diethyl 2-(4-phenylphenoxy)propanedioate
• CAS: 97080-73-4
• 化学式: C₁₉H₂₀O₅
• 分子量: 328.365
• InChiKey: VEAXEDJUVBUHLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.23
• 重原子数：
  24.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  61.83
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  diethyl 2-(4-phenylphenoxy)malonate 在 四(三苯基膦)钯 、 sodium hydride 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 48.33h， 生成 diethyl 2-(4-phenylphenoxy)-2-(4-phenylbenzyl)malonate
  参考文献：
  名称：

  Identification of the First PPARα/γ Dual Agonist Able To Bind to Canonical and Alternative Sites of PPARγ and To Inhibit Its Cdk5-Mediated Phosphorylation

  摘要：

  A new series of derivatives of the PPAR alpha/gamma dual agonist 1 allowed us to identify the ligand (S)-6 as a potent partial agonist of both PPAR alpha and gamma subtypes. X-ray studies in PPAR gamma revealed two different binding modes of (S)-6 to the canonical site. However, (S)-6 was also able to bind an alternative site as demonstrated by transactivation assay in the presence of a canonical PPAR gamma antagonist and supported from docking experiments. This compound did not activate the PPAR gamma-dependent program of adipocyte differentiation inducing a very less severe lipid accumulation compared to rosiglitazone but increased the insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Finally, (S)-6 inhibited the Cdk5-mediated phosphorylation of PPAR gamma at serine 273 that is currently considered the mechanism by which some PPAR gamma partial agonists exert antidiabetic effects similar to thiazolidinediones, without showing their typical side effects. This is the first PPAR alpha/gamma dual agonist reported to show this inhibitory effect representing the potential lead of a new class of drugs for treatment of dyslipidemic type 2 diabetes.

  DOI：

  10.1021/acs.jmedchem.8b00835
• 作为产物：
  描述：

  氯代丙二酸二乙酯 、 对羟基联苯 在 sodium 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 6.0h， 以78%的产率得到diethyl 2-(4-phenylphenoxy)malonate
  参考文献：
  名称：

  Identification of the First PPARα/γ Dual Agonist Able To Bind to Canonical and Alternative Sites of PPARγ and To Inhibit Its Cdk5-Mediated Phosphorylation

  摘要：

  A new series of derivatives of the PPAR alpha/gamma dual agonist 1 allowed us to identify the ligand (S)-6 as a potent partial agonist of both PPAR alpha and gamma subtypes. X-ray studies in PPAR gamma revealed two different binding modes of (S)-6 to the canonical site. However, (S)-6 was also able to bind an alternative site as demonstrated by transactivation assay in the presence of a canonical PPAR gamma antagonist and supported from docking experiments. This compound did not activate the PPAR gamma-dependent program of adipocyte differentiation inducing a very less severe lipid accumulation compared to rosiglitazone but increased the insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Finally, (S)-6 inhibited the Cdk5-mediated phosphorylation of PPAR gamma at serine 273 that is currently considered the mechanism by which some PPAR gamma partial agonists exert antidiabetic effects similar to thiazolidinediones, without showing their typical side effects. This is the first PPAR alpha/gamma dual agonist reported to show this inhibitory effect representing the potential lead of a new class of drugs for treatment of dyslipidemic type 2 diabetes.

  DOI：

  10.1021/acs.jmedchem.8b00835

文献信息

• GB916242
  申请人：——

  公开号：——

  公开（公告）日：——
• A New Antidiabetic Agent Showing Short- and Long-Term Effects Due to Peroxisome Proliferator-Activated Receptor Alpha/Gamma Dual Agonism and Mitochondrial Pyruvate Carrier Inhibition
  作者：Antonio Laghezza、Carmen Cerchia、Massimo Genovese、Rosalba Leuci、Erica Pranzini、Alice Santi、Leonardo Brunetti、Luca Piemontese、Paolo Tortorella、Abanish Biswas、Ravi Pratap Singh、Suhas Tambe、Sudeep CA、Ashok Kumar Pattnaik、Venkatesan Jayaprakash、Paolo Paoli、Antonio Lavecchia、Fulvio Loiodice

  DOI：10.1021/acs.jmedchem.2c02093

  日期：2023.3.9
• Identification of the First PPARα/γ Dual Agonist Able To Bind to Canonical and Alternative Sites of PPARγ and To Inhibit Its Cdk5-Mediated Phosphorylation
  作者：Antonio Laghezza、Luca Piemontese、Carmen Cerchia、Roberta Montanari、Davide Capelli、Marco Giudici、Maurizio Crestani、Paolo Tortorella、Franck Peiretti、Giorgio Pochetti、Antonio Lavecchia、Fulvio Loiodice

  DOI：10.1021/acs.jmedchem.8b00835

  日期：2018.9.27

  A new series of derivatives of the PPAR alpha/gamma dual agonist 1 allowed us to identify the ligand (S)-6 as a potent partial agonist of both PPAR alpha and gamma subtypes. X-ray studies in PPAR gamma revealed two different binding modes of (S)-6 to the canonical site. However, (S)-6 was also able to bind an alternative site as demonstrated by transactivation assay in the presence of a canonical PPAR gamma antagonist and supported from docking experiments. This compound did not activate the PPAR gamma-dependent program of adipocyte differentiation inducing a very less severe lipid accumulation compared to rosiglitazone but increased the insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Finally, (S)-6 inhibited the Cdk5-mediated phosphorylation of PPAR gamma at serine 273 that is currently considered the mechanism by which some PPAR gamma partial agonists exert antidiabetic effects similar to thiazolidinediones, without showing their typical side effects. This is the first PPAR alpha/gamma dual agonist reported to show this inhibitory effect representing the potential lead of a new class of drugs for treatment of dyslipidemic type 2 diabetes.