3-[(S)-2-(Cyclopropylmethyl-amino)-1-methyl-ethyl]-1-(2,6-difluoro-benzyl)-5-(3-methoxy-phenyl)-6-methyl-1H-pyrimidine-2,4-dione | 352297-89-3

• 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: 3-[(S)-2-(Cyclopropylmethyl-amino)-1-methyl-ethyl]-1-(2,6-difluoro-benzyl)-5-(3-methoxy-phenyl)-6-methyl-1H-pyrimidine-2,4-dione
• 英文别名: 3-[(2S)-1-(cyclopropylmethylamino)propan-2-yl]-1-[(2,6-difluorophenyl)methyl]-5-(3-methoxyphenyl)-6-methylpyrimidine-2,4-dione
• CAS: 352297-89-3
• 化学式: C₂₆H₂₉F₂N₃O₃
• 分子量: 469.531
• InChiKey: UUOQULXFEYRBEL-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 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：

  聚合甲醛 、 3-[(S)-2-(Cyclopropylmethyl-amino)-1-methyl-ethyl]-1-(2,6-difluoro-benzyl)-5-(3-methoxy-phenyl)-6-methyl-1H-pyrimidine-2,4-dione 在 sodium tetrahydroborate 作用下， 以 甲醇 、 水 为溶剂， 反应 0.25h， 生成 3-[(S)-2-(Cyclopropylmethyl-methyl-amino)-1-methyl-ethyl]-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：

  3-[2-N-Boc-amino-1-(S)-methylethyl]-5-bromo-1-(2,6-difluorobenzyl)-6-methyluracil 在 sodium tetrahydroborate 、 四(三苯基膦)钯 、 potassium carbonate 、 三氟乙酸 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 20.0h， 生成 3-[(S)-2-(Cyclopropylmethyl-amino)-1-methyl-ethyl]-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

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.