| 618902-02-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• CAS: 618902-02-6
• 化学式: C₂₇H₃₁F₂N₃O₅
• 分子量: 515.557
• InChiKey: GAUJIDROXXUMDP-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.41
• 重原子数：
  37.0
• 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：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以95%的产率得到3-[(2S)-1-aminopropan-2-yl]-1-[(2,6-difluorophenyl)methyl]-5-(3-methoxyphenyl)-6-methylpyrimidine-2,4-dione
  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 、 乙醇 、 甲苯 为溶剂， 反应 61.0h， 生成
  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

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.