ethyl 4-(4-(benzyloxy)-3-methoxyphenyl)-3,6-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate | 1431221-61-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: ethyl 4-(4-(benzyloxy)-3-methoxyphenyl)-3,6-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
• 英文别名: Ethyl 4-(3-methoxy-4-phenylmethoxyphenyl)-3,6-dimethyl-2-oxo-1,4-dihydropyrimidine-5-carboxylate；ethyl 4-(3-methoxy-4-phenylmethoxyphenyl)-3,6-dimethyl-2-oxo-1,4-dihydropyrimidine-5-carboxylate
• CAS: 1431221-61-2
• 化学式: C₂₃H₂₆N₂O₅
• 分子量: 410.47
• InChiKey: HISJWAKJMJWQPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-苄氧基-3-甲氧基苯甲醛 在 potassium carbonate 、 zinc(II) chloride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.0h， 生成 ethyl 4-(4-(benzyloxy)-3-methoxyphenyl)-3,6-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
  参考文献：
  名称：

  Identification of New Nonsteroidal RORα Ligands; Related Structure–Activity Relationships and Docking Studies

  摘要：

  A high throughput screen was developed to identify novel, nonsteroidal ROR alpha agonists. Among the validated hit compounds, the 4-(-(benzyloxy)phenyl)-5-carbonyl-2-oxo-1,2,3,4-tetrahydropyrimidine scaffold was the most prominent Among the numerous analogues tested, compounds 8 and 9 showed the highest activity. Key structure-activity relationships (SAR) were established, where benzyl and urea moieties were both identified as very important elements to maintain the activity. Most notably, the SAR were consistent with the binding mode of the compound 8 (S-isomer) in the ROR alpha docking model that was developed in this program. As predicted by the model, the urea moiety is engaged in the formation of key hydrogen bonds with the backbone of Tyr380 and Asp382. The benzyl group is located in a wide hydrophobic pocket. The structural relationships reported in this letter will help in further optimization of this compound series and will provide novel synthetic probes helpful for elucidation of complex ROR alpha physiopathology.

  DOI：

  10.1021/ml300471d

文献信息

• Identification of New Nonsteroidal RORα Ligands; Related Structure–Activity Relationships and Docking Studies
  作者：Mathieu Dubernet、Nicolas Duguet、Lionel Colliandre、Christophe Berini、Stéphane Helleboid、Marilyne Bourotte、Matthieu Daillet、Lucie Maingot、Sébastien Daix、Jean-François Delhomel、Luc Morin-Allory、Sylvain Routier、Robert Walczak

  DOI：10.1021/ml300471d

  日期：2013.6.13

  A high throughput screen was developed to identify novel, nonsteroidal ROR alpha agonists. Among the validated hit compounds, the 4-(-(benzyloxy)phenyl)-5-carbonyl-2-oxo-1,2,3,4-tetrahydropyrimidine scaffold was the most prominent Among the numerous analogues tested, compounds 8 and 9 showed the highest activity. Key structure-activity relationships (SAR) were established, where benzyl and urea moieties were both identified as very important elements to maintain the activity. Most notably, the SAR were consistent with the binding mode of the compound 8 (S-isomer) in the ROR alpha docking model that was developed in this program. As predicted by the model, the urea moiety is engaged in the formation of key hydrogen bonds with the backbone of Tyr380 and Asp382. The benzyl group is located in a wide hydrophobic pocket. The structural relationships reported in this letter will help in further optimization of this compound series and will provide novel synthetic probes helpful for elucidation of complex ROR alpha physiopathology.