1-(2,6-Difluoro-benzyl)-5-(3-methoxy-phenyl)-6-methyl-3-pyrrolidin-3-yl-1H-pyrimidine-2,4-dione | 352298-02-3

• 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: 1-(2,6-Difluoro-benzyl)-5-(3-methoxy-phenyl)-6-methyl-3-pyrrolidin-3-yl-1H-pyrimidine-2,4-dione
• 英文别名: 1-[(2,6-difluorophenyl)methyl]-5-(3-methoxyphenyl)-6-methyl-3-pyrrolidin-3-ylpyrimidine-2,4-dione
• CAS: 352298-02-3
• 化学式: C₂₃H₂₃F₂N₃O₃
• 分子量: 427.451
• InChiKey: JSEWNRZOBBMHTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  苯甲醛 、 1-(2,6-Difluoro-benzyl)-5-(3-methoxy-phenyl)-6-methyl-3-pyrrolidin-3-yl-1H-pyrimidine-2,4-dione 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 3-(1-Benzyl-pyrrolidin-3-yl)-1-(2,6-difluoro-benzyl)-5-(3-methoxy-phenyl)-6-methyl-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis and Structure–activity relationships of 1-arylmethyl-3-(1-methyl-2-amino)ethyl-5-aryl-6-methyluracils as antagonists of the human GnRH Receptor

  摘要：

  A new class of small molecule GnRH antagonists, the 1-arylmethyl-3-(1-methyl-2-amino)ethyl-5-aryl-6-methyluracils, was designed and a novel stereoselective synthesis for these compounds was developed. The stereochemical integrities of key intermediates (S)-6 and (R)-6 were confirmed by a combination of X-ray crystallography and chiral HPLC determinations. SAR Studies were performed, which allowed the identification of derivatives (R)-9f, (R)-9h and (R)-12 as potent hGnRH antagonists (K-i=20 nM). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00619-x
• 作为产物：
  描述：

  在 四(三苯基膦)钯 、 potassium carbonate 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 16.0h， 生成 1-(2,6-Difluoro-benzyl)-5-(3-methoxy-phenyl)-6-methyl-3-pyrrolidin-3-yl-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis and Structure–activity relationships of 1-arylmethyl-3-(1-methyl-2-amino)ethyl-5-aryl-6-methyluracils as antagonists of the human GnRH Receptor

  摘要：

  A new class of small molecule GnRH antagonists, the 1-arylmethyl-3-(1-methyl-2-amino)ethyl-5-aryl-6-methyluracils, was designed and a novel stereoselective synthesis for these compounds was developed. The stereochemical integrities of key intermediates (S)-6 and (R)-6 were confirmed by a combination of X-ray crystallography and chiral HPLC determinations. SAR Studies were performed, which allowed the identification of derivatives (R)-9f, (R)-9h and (R)-12 as potent hGnRH antagonists (K-i=20 nM). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00619-x

文献信息

• Synthesis and Structure–activity relationships of 1-arylmethyl-3-(1-methyl-2-amino)ethyl-5-aryl-6-methyluracils as antagonists of the human GnRH Receptor
  作者：Fabio C. Tucci、Yun-Fei Zhu、Zhiqiang Guo、Timothy D. Gross、Patrick J. Connors、R.Scott Struthers、Greg J. Reinhart、John Saunders、Chen Chen

  DOI：10.1016/s0960-894x(03)00619-x

  日期：2003.10

  A new class of small molecule GnRH antagonists, the 1-arylmethyl-3-(1-methyl-2-amino)ethyl-5-aryl-6-methyluracils, was designed and a novel stereoselective synthesis for these compounds was developed. The stereochemical integrities of key intermediates (S)-6 and (R)-6 were confirmed by a combination of X-ray crystallography and chiral HPLC determinations. SAR Studies were performed, which allowed the identification of derivatives (R)-9f, (R)-9h and (R)-12 as potent hGnRH antagonists (K-i=20 nM). (C) 2003 Elsevier Ltd. All rights reserved.