(2RS,3RS)-phenyl 2-(benzo[d][1,3]dioxol-5-yl)-3-hydroxy-4-oxo-3,4-dihydropyridine-1(2H)-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: (2RS,3RS)-phenyl 2-(benzo[d][1,3]dioxol-5-yl)-3-hydroxy-4-oxo-3,4-dihydropyridine-1(2H)-carboxylate
• 化学式: C₁₉H₁₅NO₆
• 分子量: 353.331
• InChiKey: APJBFEJHQOAULU-MSOLQXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.41
• 重原子数：
  26.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  85.3
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2RS,3RS)-phenyl 2-(benzo[d][1,3]dioxol-5-yl)-3-hydroxy-4-oxo-3,4-dihydropyridine-1(2H)-carboxylate 在 咪唑 、 sodium methylate 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 21.0h， 生成 (2RS,3RS)-3-((tert-butyldimethylsilyl)oxy)-1-cinnamoyl-2-methyl-2,3-dihydropyridin-4(1H)-one
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationship Studies of Novel Dihydropyridones as Androgen Receptor Modulators

  摘要：

  A library of 3-hydroxy-2,3-dihydropyridones was synthesized, and their activities as antiandrogens were tested in the human prostate cancer cell line LNCaP. Structure-activity relationship (SAR) studies resulted in the identification of a potent compound whose activity is comparable to that of MDV3100. Homology modeling and molecular mechanics were used to build a structural model of the androgen receptor ligand binding domain and to investigate the structural basis of the antagonism. The model is qualitatively consistent with the observed SAR. Moreover, the enrichment plot shows that screening with the model performs significantly better than random screening. Therefore, the model probably represents a realistic conformation of the antagonist form and can be utilized for structure-based design of novel antiandrogens.

  DOI：

  10.1021/jm301714s
• 作为产物：
  描述：

  magnesium,5H-1,3-benzodioxol-5-ide,bromide 在 四氧化锇 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 水 、 丙酮 、 叔丁醇 为溶剂， 反应 0.42h， 生成 (2RS,3RS)-phenyl 2-(benzo[d][1,3]dioxol-5-yl)-3-hydroxy-4-oxo-3,4-dihydropyridine-1(2H)-carboxylate
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationship Studies of Novel Dihydropyridones as Androgen Receptor Modulators

  摘要：

  A library of 3-hydroxy-2,3-dihydropyridones was synthesized, and their activities as antiandrogens were tested in the human prostate cancer cell line LNCaP. Structure-activity relationship (SAR) studies resulted in the identification of a potent compound whose activity is comparable to that of MDV3100. Homology modeling and molecular mechanics were used to build a structural model of the androgen receptor ligand binding domain and to investigate the structural basis of the antagonism. The model is qualitatively consistent with the observed SAR. Moreover, the enrichment plot shows that screening with the model performs significantly better than random screening. Therefore, the model probably represents a realistic conformation of the antagonist form and can be utilized for structure-based design of novel antiandrogens.

  DOI：

  10.1021/jm301714s

文献信息

• Synthesis and Structure–Activity Relationship Studies of Novel Dihydropyridones as Androgen Receptor Modulators
  作者：Antonella Pepe、Michael Pamment、Yeong Sang Kim、Sunmin Lee、Min-Jung Lee、Kristin Beebe、Anton Filikov、Len Neckers、Jane B. Trepel、Sanjay V. Malhotra

  DOI：10.1021/jm301714s

  日期：2013.11.14

  A library of 3-hydroxy-2,3-dihydropyridones was synthesized, and their activities as antiandrogens were tested in the human prostate cancer cell line LNCaP. Structure-activity relationship (SAR) studies resulted in the identification of a potent compound whose activity is comparable to that of MDV3100. Homology modeling and molecular mechanics were used to build a structural model of the androgen receptor ligand binding domain and to investigate the structural basis of the antagonism. The model is qualitatively consistent with the observed SAR. Moreover, the enrichment plot shows that screening with the model performs significantly better than random screening. Therefore, the model probably represents a realistic conformation of the antagonist form and can be utilized for structure-based design of novel antiandrogens.