1-(2,6-Difluorobenzyl)-5-(3-methoxyphenyl)-6-methyl-3-[N-methyl-N-(2-pyridylethyl)aminoethyl]uracil

• 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-Difluorobenzyl)-5-(3-methoxyphenyl)-6-methyl-3-[N-methyl-N-(2-pyridylethyl)aminoethyl]uracil
• 英文别名: 1-(2,6-Difluoro-benzyl)-5-(3-methoxy-phenyl)-6-methyl-3-{2-[methyl-(2-pyridin-2-yl-ethyl)-amino]-ethyl}-1H-pyrimidine-2,4-dione；1-[(2,6-difluorophenyl)methyl]-5-(3-methoxyphenyl)-6-methyl-3-[2-[methyl(2-pyridin-2-ylethyl)amino]ethyl]pyrimidine-2,4-dione
• 化学式: C₂₉H₃₀F₂N₄O₃
• 分子量: 520.579
• InChiKey: JWKDAXNMZQKVPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  66
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-(2-甲基氨基乙基)吡啶 在 四(三苯基膦)钯 、 三乙酰氧基硼氢化钠 、 sodium carbonate 作用下， 以 乙醇 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 2.0h， 生成 1-(2,6-Difluorobenzyl)-5-(3-methoxyphenyl)-6-methyl-3-[N-methyl-N-(2-pyridylethyl)aminoethyl]uracil
  参考文献：
  名称：

  Identification of 1-Arylmethyl-3- (2-aminoethyl)-5-aryluracil as Novel Gonadotropin-Releasing Hormone Receptor Antagonists

  摘要：

  Based on SAR from hicyclic GnRH antagonists such as 6-aminomethyl-7-arylpyrrolo[1,2-a]pyrimid-4-ones (1) and 2-aryl-3-aminomethylimidazolo[1,2-a]pyrimid-5-ones (2a,b), a series of novel uracil compounds (4) were derived as the GnRH antagonists. Their syntheses and initial SAR are discussed herein. This is the first time that monocycle-based GnRH receptor antagonists are reported.

  DOI：

  10.1021/jm034041s

文献信息

• Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
  申请人：Neurocrine Biosciences, Inc.

  公开号：US20020132820A1

  公开（公告）日：2002-09-19

  GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: 1 wherein A, Q, R 1 , R 2 , R 3a , R 3b , R 4 , R 5 , R 6 and n are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

  GnRH受体拮抗剂被披露，可用于治疗男性和女性的各种与性激素相关的疾病。本发明的化合物具有以下结构：其中A、Q、R1、R2、R3a、R3b、R4、R5、R6和n的定义如本文所述，包括立体异构体、前药和其药用可接受盐。还披露了含有本发明化合物与药用可接受载体结合的组合物，以及与使用这些组合物拮抗需要的受试者中的促性腺激素释放激素相关的方法。
• Identification of 1-Arylmethyl-3- (2-aminoethyl)-5-aryluracil as Novel Gonadotropin-Releasing Hormone Receptor Antagonists
  作者：Yun-Fei Zhu、Timothy D. Gross、Zhiqiang Guo、Patrick J. Connors,、Yinghong Gao、Fabio C. Tucci、R. Scott Struthers、Greg J. Reinhart、John Saunders、Ta Kung Chen、Anne L. Killam Bonneville、Chen

  DOI：10.1021/jm034041s

  日期：2003.5.1

  Based on SAR from hicyclic GnRH antagonists such as 6-aminomethyl-7-arylpyrrolo[1,2-a]pyrimid-4-ones (1) and 2-aryl-3-aminomethylimidazolo[1,2-a]pyrimid-5-ones (2a,b), a series of novel uracil compounds (4) were derived as the GnRH antagonists. Their syntheses and initial SAR are discussed herein. This is the first time that monocycle-based GnRH receptor antagonists are reported.
• GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS AND METHODS RELATING THERETO
  申请人：NEUROCRINE BIOSCIENCES, INC.

  公开号：EP1255738B1

  公开（公告）日：2012-03-07
• US6608197B2
  申请人：——

  公开号：US6608197B2

  公开（公告）日：2003-08-19
• US6872728B2
  申请人：——

  公开号：US6872728B2

  公开（公告）日：2005-03-29