2-(1-methyl-1-methoxycarbonylethyl)-6-bromo-7-methylimidazolo[1,2-a]pyrimid-5-one | 335278-75-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并[1，2-a]嘧啶
• 英文名称: 2-(1-methyl-1-methoxycarbonylethyl)-6-bromo-7-methylimidazolo[1,2-a]pyrimid-5-one
• 英文别名: 5-bromo-6-methyl-2-(1-methoxycarbonyl-1-methylethyl)-7H-imidazolo[1,2-a]pyrimid-4-one；methyl 2-(6-bromo-7-methyl-5-oxo-1H-imidazo[1,2-a]pyrimidin-2-yl)-2-methylpropanoate
• CAS: 335278-75-6
• 化学式: C₁₂H₁₄BrN₃O₃
• 分子量: 328.165
• InChiKey: FMRALICEHBWSCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  71
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(1-methyl-1-methoxycarbonylethyl)-6-bromo-7-methylimidazolo[1,2-a]pyrimid-5-one 在 四(三苯基膦)钯 、 四丁基氟化铵 、 potassium carbonate 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 6.0h， 生成 2-(1-methyl-1-methoxycarbonylethyl)-6-(3-methoxyphenyl)-7-methyl-8-(2-fluorobenzyl)imidazolo[1,2-a]pyrimid-5-one
  参考文献：
  名称：

  Design and Structure−Activity Relationships of 2-Alkyl-3-aminomethyl-6-(3-methoxyphenyl)-7-methyl-8-(2-fluorobenzyl)imidazolo[1,2-a]pyrimid-5-ones as Potent GnRH Receptor Antagonists

  摘要：

  SAR studies of 7-phenylpyrrolo[1,2-a]pyrimid-4-ones 1 and 2, and 2-phenylimidazolo[1,2-a]-pyrimidines 3 and 4, as nonpeptide human GnRH receptor antagonists, lead us to believe that the aromatic ring at position-2 of 4 is no longer crucial for the binding once an aryl group is incorporated at postion-6. We report here the use of a 2-alkyl group on the imidazolo[1,2-a]-pyrimidone core to generate potent GnRH receptor antagonists. This discovery enabled us to obtain smaller but equally potent GnRH receptor antagonists.

  DOI：

  10.1021/jm0205402
• 作为产物：
  描述：

  2,2-二甲基乙酰乙酸甲酯 在 三氯化铝 、 溴 、 sodium hydride 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 2-(1-methyl-1-methoxycarbonylethyl)-6-bromo-7-methylimidazolo[1,2-a]pyrimid-5-one
  参考文献：
  名称：

  Design and Structure−Activity Relationships of 2-Alkyl-3-aminomethyl-6-(3-methoxyphenyl)-7-methyl-8-(2-fluorobenzyl)imidazolo[1,2-a]pyrimid-5-ones as Potent GnRH Receptor Antagonists

  摘要：

  SAR studies of 7-phenylpyrrolo[1,2-a]pyrimid-4-ones 1 and 2, and 2-phenylimidazolo[1,2-a]-pyrimidines 3 and 4, as nonpeptide human GnRH receptor antagonists, lead us to believe that the aromatic ring at position-2 of 4 is no longer crucial for the binding once an aryl group is incorporated at postion-6. We report here the use of a 2-alkyl group on the imidazolo[1,2-a]-pyrimidone core to generate potent GnRH receptor antagonists. This discovery enabled us to obtain smaller but equally potent GnRH receptor antagonists.

  DOI：

  10.1021/jm0205402

文献信息

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

  公开号：US06537998B1

  公开（公告）日：2003-03-25

  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: wherein Ar, A, B, Q, R1, R2, R3a, R3b, R6, R7 and m are as defined herein, including stereoisomers, prodrugs and pharmaceutical 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受体拮抗剂被披露出来，对男性和女性的各种与性激素相关的疾病具有治疗作用。本发明的化合物具有以下结构：其中Ar、A、B、Q、R1、R2、R3a、R3b、R6、R7和m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的组合物，与药用可接受载体结合，以及与其相关的用于拮抗需要者体内促性腺激素释放激素的方法。
• GONADOTROPIN RELEASING HORMONE RECEPTOR ANTAGONISTS AND THEIR RELATED METHODS OF USE
  申请人：NEUROCRINE BIOSCIENCES, INC.

  公开号：EP1220857B1

  公开（公告）日：2005-09-21
• Design and Structure−Activity Relationships of 2-Alkyl-3-aminomethyl-6-(3-methoxyphenyl)-7-methyl-8-(2-fluorobenzyl)imidazolo[1,2-<i>a</i>]pyrimid-5-ones as Potent GnRH Receptor Antagonists
  作者：Yun-Fei Zhu、Zhiqiang Guo、Timothy D. Gross、Yinghong Gao、Patrick J. Connors,、R. Scott Struthers、Qiu Xie、Fabio C. Tucci、Greg J. Reinhart、Dongpei Wu、John Saunders、Chen

  DOI：10.1021/jm0205402

  日期：2003.4.1

  SAR studies of 7-phenylpyrrolo[1,2-a]pyrimid-4-ones 1 and 2, and 2-phenylimidazolo[1,2-a]-pyrimidines 3 and 4, as nonpeptide human GnRH receptor antagonists, lead us to believe that the aromatic ring at position-2 of 4 is no longer crucial for the binding once an aryl group is incorporated at postion-6. We report here the use of a 2-alkyl group on the imidazolo[1,2-a]-pyrimidone core to generate potent GnRH receptor antagonists. This discovery enabled us to obtain smaller but equally potent GnRH receptor antagonists.