5-bromo-1-[2-bromo-6-fluorobenzyl]-6-methylpyrimidine-2,4(1H,3H)-dione | 832711-70-3

• 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: 5-bromo-1-[2-bromo-6-fluorobenzyl]-6-methylpyrimidine-2,4(1H,3H)-dione
• 英文别名: 5-Bromo-1-[(2-chloro-6-fluorophenyl)methyl]-6-methylpyrimidine-2,4-dione
• CAS: 832711-70-3
• 化学式: C₁₂H₉BrClFN₂O₂
• 分子量: 347.571
• InChiKey: LMWRPCWHBZUZCT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-bromo-1-[2-bromo-6-fluorobenzyl]-6-methylpyrimidine-2,4(1H,3H)-dione 、 Boc-D-苯甘氨醇 在 偶氮二甲酸二叔丁酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以76%的产率得到3-[2(R)-tert-butoxycarbonylamino-2-phenylethyl]-5-bromo-1-[2-bromo-6-fluorobenzyl]-6-methylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  [EN] PYRIMIDINE-2,4-DIONE DERIVATIVES AS GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS
  [FR] DERIVES DE PYRIMIDINE-2,4-DIONE, SERVANT D'ANTAGONISTES AU RECEPTEUR DE L'HORMONE DE LIBERATION DE LA GONADOTROPINE

  摘要：

  GnRH受体拮抗剂已被披露，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结构式（I），其中R1a、R1b、R2a、R2b、R3、R4、R5、R6、R7和X如本文所定义，包括立体异构体、前药和其药用盐。此外，还披露了含有本发明化合物的组合物，该组合物与药用载体结合，以及涉及使用该组合物来拮抗需要此类治疗的受试者的促性腺激素释放激素的方法。

  公开号：

  WO2005007164A1
• 作为产物：
  描述：

  在 溴 作用下， 以 溶剂黄146 为溶剂， 反应 2.0h， 生成 5-bromo-1-[2-bromo-6-fluorobenzyl]-6-methylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Discovery of Sodium R-(+)-4-{2-[5-(2-Fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate (Elagolix), a Potent and Orally Available Nonpeptide Antagonist of the Human Gonadotropin-Releasing Hormone Receptor

  摘要：

  The discovery of novel uracil phenylethylamines bearing a butyric acid as potent human gonadotropin-releasing hormone receptor (hGnRH-R) antagonists is described. A major focus of this optimization was to improve the CYP3A4 inhibition liability of these uracils while maintaining their GnRH-R potency. R-4-{2-[5-(2-Fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyric acid sodium salt, 10b (elagolix), was identified as a potent and selective hGnRH-R antagonist. Oral administration of 10b suppressed luteinizing hormone in castrated macaques. These efforts led to the identification of 10b as a clinical compound for the treatment of endometriosis.

  DOI：

  10.1021/jm8006454

文献信息

• [EN] PYRIMIDINE-2,4-DIONE DERIVATIVES AS GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE PYRIMIDINE-2,4-DIONE, SERVANT D'ANTAGONISTES AU RECEPTEUR DE L'HORMONE DE LIBERATION DE LA GONADOTROPINE
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2005007164A1

  公开（公告）日：2005-01-27

  GnRH receptor antagonists are disclosed that 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 formula (I) wherein R1a, R1b, R2a, R2b, R3, R4, R5, R6, R7 and X 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受体拮抗剂已被披露，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结构式（I），其中R1a、R1b、R2a、R2b、R3、R4、R5、R6、R7和X如本文所定义，包括立体异构体、前药和其药用盐。此外，还披露了含有本发明化合物的组合物，该组合物与药用载体结合，以及涉及使用该组合物来拮抗需要此类治疗的受试者的促性腺激素释放激素的方法。
• Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
  申请人：Zhu Yun-Fei

  公开号：US20050043338A1

  公开（公告）日：2005-02-24

  GnRH receptor antagonists are disclosed that 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 R 1a , R 1b , R 2a , R 2b , R 3 , R 4 , R 5 , R 6 , R 7 and X 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.

  本发明披露了GnRH受体拮抗剂，可用于治疗男性和女性的各种性激素相关疾病。本发明的化合物具有以下结构：其中R1a、R1b、R2a、R2b、R3、R4、R5、R6、R7和X的定义如本文所述，包括立体异构体、前药和其药学上可接受的盐。还披露了含有本发明化合物的组合物与药学上可接受的载体，以及与其相关的方法，用于对需要拮抗促性腺激素释放激素的受体的患者进行治疗。
• PYRIMIDINE-2,4-DIONE DERIVATIVES AS GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS
  申请人：NEUROCRINE BIOSCIENCES, INC.

  公开号：EP1660091A1

  公开（公告）日：2006-05-31
• US7071200B2
  申请人：——

  公开号：US7071200B2

  公开（公告）日：2006-07-04
• US7329669B2
  申请人：——

  公开号：US7329669B2

  公开（公告）日：2008-02-12