3-[2-N-Boc-amino-1-(R)-methylethyl]-1-(2,6-difluorobenzyl)-5-(2-fluoro-3-methoxyphenyl)-6-methyluracil | 675606-03-8

• 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-[2-N-Boc-amino-1-(R)-methylethyl]-1-(2,6-difluorobenzyl)-5-(2-fluoro-3-methoxyphenyl)-6-methyluracil
• 英文别名: tert-butyl N-[(2R)-2-[3-[(2,6-difluorophenyl)methyl]-5-(2-fluoro-3-methoxyphenyl)-4-methyl-2,6-dioxopyrimidin-1-yl]propyl]carbamate
• CAS: 675606-03-8
• 化学式: C₂₇H₃₀F₃N₃O₅
• 分子量: 533.548
• InChiKey: JDFYKQDNKRNHIU-OAHLLOKOSA-N

物化性质

• 密度：
  1.279±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.55
• 重原子数：
  38.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  91.56
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  3-[2-N-Boc-amino-1-(R)-methylethyl]-1-(2,6-difluorobenzyl)-5-(2-fluoro-3-methoxyphenyl)-6-methyluracil 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以95%的产率得到3-[2-amino-1-(R)-methylethyl]-1-(2,6-difluorobenzyl)-5-(2-fluoro-3-methoxyphenyl)-6-methyluracil
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 1-Arylmethyl-5-aryl-6-methyluracils as Potent Gonadotropin-Releasing Hormone Receptor Antagonists

  摘要：

  Based on the SAR from bicyclic gonadotropin-releasing hormone (GnRH) antagonists such as 6-aminomethyl-7-aryl-pyrrolo[1,2-alpha]pyrimid-4-ones (5) and 2-aryl-3-aminomethyl-imidazolo[1,2-alpha]pyrimid-5-ones (6a,b), a series of novel uracil compounds (8) were derived as GnRH antagonists. The synthesis and SAR studies of 6-methyluracils as human GnRH receptor antagonists are discussed herein. Introduction of a small methyl substituent at the beta-position of the N3 side-chain improved the GnRH binding potency by 5-10-fold. Introduction of a methyl group of (R)-configuration at the alpha-carbon of the N-3 side-chain gave a modest improvement in binding affinity over the unsubstituted ethylene analogues. This modification enabled us to make uracil compounds without the labile 2-pyridylethyl motif on the basic nitrogen while still maintained excellent potency against the hGnRH receptor.

  DOI：

  10.1021/jm030472z
• 作为产物：
  描述：

  (2,6-二氟-苄基)-脲 在 吡啶 、 四(三苯基膦)钯 、 溴 、 potassium carbonate 、 溶剂黄146 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 50.0h， 生成 3-[2-N-Boc-amino-1-(R)-methylethyl]-1-(2,6-difluorobenzyl)-5-(2-fluoro-3-methoxyphenyl)-6-methyluracil
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 1-Arylmethyl-5-aryl-6-methyluracils as Potent Gonadotropin-Releasing Hormone Receptor Antagonists

  摘要：

  Based on the SAR from bicyclic gonadotropin-releasing hormone (GnRH) antagonists such as 6-aminomethyl-7-aryl-pyrrolo[1,2-alpha]pyrimid-4-ones (5) and 2-aryl-3-aminomethyl-imidazolo[1,2-alpha]pyrimid-5-ones (6a,b), a series of novel uracil compounds (8) were derived as GnRH antagonists. The synthesis and SAR studies of 6-methyluracils as human GnRH receptor antagonists are discussed herein. Introduction of a small methyl substituent at the beta-position of the N3 side-chain improved the GnRH binding potency by 5-10-fold. Introduction of a methyl group of (R)-configuration at the alpha-carbon of the N-3 side-chain gave a modest improvement in binding affinity over the unsubstituted ethylene analogues. This modification enabled us to make uracil compounds without the labile 2-pyridylethyl motif on the basic nitrogen while still maintained excellent potency against the hGnRH receptor.

  DOI：

  10.1021/jm030472z