(R)-1-(2-fluoro-6-(methylsulfonyl)benzyl)-3-(2-amino-2-phenylethyl)-5-(2-chlorophenyl)pyrimidine-2,4(1H,3H)-dione | 855230-30-7

• 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: (R)-1-(2-fluoro-6-(methylsulfonyl)benzyl)-3-(2-amino-2-phenylethyl)-5-(2-chlorophenyl)pyrimidine-2,4(1H,3H)-dione
• 英文别名: 3-[(2R)-2-amino-2-phenylethyl]-5-(2-chlorophenyl)-1-[(2-fluoro-6-methylsulfonylphenyl)methyl]pyrimidine-2,4-dione
• CAS: 855230-30-7
• 化学式: C₂₆H₂₃ClFN₃O₄S
• 分子量: 528.004
• InChiKey: WXUZGCQTOVWUDO-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-1-(2-fluoro-6-(methylsulfonyl)benzyl)-3-(2-amino-2-phenylethyl)-5-(2-chlorophenyl)pyrimidine-2,4(1H,3H)-dione 、 4-溴丁酸甲酯 在 sodium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 methyl (R)-4-((2-(5-(2-chlorophenyl)-3-(2-fluoro-6-(methylsulfonyl)benzyl)-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)-1-phenylethyl)amino)butanoate
  参考文献：
  名称：

  Potent and orally bioavailable zwitterion GnRH antagonists with low CYP3A4 inhibitory activity

  摘要：

  Incorporation of a carboxylic acid into a series of uracil derivatives as hGnRH-R antagonists resulted in a significant reduction of CYP3A4 inhibitory activity. Highly potent hGnRH antagonists with low CYP3A4 inhibitory liability, such as 8a and 8d, were identified. Thus, 8a had a K(i) of 2.2 nM at GnRH-R and an IC(50) of 36 mu M at CYP3A4. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.04.036
• 作为产物：
  描述：

  tert-butyl N-[(1R)-2-[5-bromo-3-[(2,6-difluorophenyl)methyl]-2,6-dioxopyrimidin-1-yl]-1-phenylethyl]carbamate 在 Oxone 、 四(三苯基膦)钯 、 sodium carbonate 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 生成 (R)-1-(2-fluoro-6-(methylsulfonyl)benzyl)-3-(2-amino-2-phenylethyl)-5-(2-chlorophenyl)pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Uracils as potent antagonists of the human gonadotropin-releasing hormone receptor without atropisomers

  摘要：

  Uracil derivatives were designed and synthesized to avoid atropisomers observed in the 6-methyluracils as antagonists of the human GnRH receptor. Optimization at the 1- and 5-positions of the uracil resulted in potent compounds such as 24 (K-i = 0.45 nM). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.057

文献信息

• Potent and orally bioavailable zwitterion GnRH antagonists with low CYP3A4 inhibitory activity
  作者：Chen Chen、Yongsheng Chen、Joseph Pontillo、Zhiqiang Guo、Charles Q. Huang、Dongpei Wu、Ajay Madan、Takung Chen、Jenny Wen、Qiu Xie、Fabio C. Tucci、Martin Rowbottom、Yun-Fei Zhu、Warren Wade、John Saunders、Haig Bozigian、R. Scott Struthers

  DOI：10.1016/j.bmcl.2008.04.036

  日期：2008.6

  Incorporation of a carboxylic acid into a series of uracil derivatives as hGnRH-R antagonists resulted in a significant reduction of CYP3A4 inhibitory activity. Highly potent hGnRH antagonists with low CYP3A4 inhibitory liability, such as 8a and 8d, were identified. Thus, 8a had a K(i) of 2.2 nM at GnRH-R and an IC(50) of 36 mu M at CYP3A4. (C) 2008 Elsevier Ltd. All rights reserved.
• Uracils as potent antagonists of the human gonadotropin-releasing hormone receptor without atropisomers
  作者：Zhiqiang Guo、Yongsheng Chen、Charles Q. Huang、Timothy D. Gross、Joseph Pontillo、Martin W. Rowbottom、John Saunders、Scott Struthers、Fabio C. Tucci、Qiu Xie、Warren Wade、Yun-Fei Zhu、Dongpei Wu、Chen Chen

  DOI：10.1016/j.bmcl.2005.03.057

  日期：2005.5

  Uracil derivatives were designed and synthesized to avoid atropisomers observed in the 6-methyluracils as antagonists of the human GnRH receptor. Optimization at the 1- and 5-positions of the uracil resulted in potent compounds such as 24 (K-i = 0.45 nM). (c) 2005 Elsevier Ltd. All rights reserved.