5-bromo-1-[2-fluoro-6-(trifluoromethyl)benzyl]pyrimidine-2,4-(1H,3H)-dione | 830346-32-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-bromo-1-[2-fluoro-6-(trifluoromethyl)benzyl]pyrimidine-2,4-(1H,3H)-dione
• 英文别名: 5-bromo-1-[2-fluoro-6-(trifluoromethyl)benzyl]pyrimidine-2,4(1H,3H)-dione；5-bromo-1-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]pyrimidine-2,4-dione
• CAS: 830346-32-2
• 化学式: C₁₂H₇BrF₄N₂O₂
• 分子量: 367.097
• InChiKey: NYORAJKDTJRDCU-UHFFFAOYSA-N

物化性质

• 密度：
  1.763±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 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：
  6

反应信息

• 作为反应物：
  描述：

  5-bromo-1-[2-fluoro-6-(trifluoromethyl)benzyl]pyrimidine-2,4-(1H,3H)-dione 在 四(三苯基膦)钯 、 sodium carbonate 、 三苯基膦 、 三氟乙酸 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 3-[2(R)-amino-2-phenylethyl]-5-(2-chlorophenyl)-1-[2-fluoro-6-(trifluoromethyl)benzyl]-pyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Uracils as potent antagonists of the human gonadotropin-releasing hormone receptor without atropisomers

  摘要：

  Uracil derivatives were designed and synthesized to avoid atropisomers observed in the 6-methyluracils as antagonists of the human GnRH receptor. Optimization at the 1- and 5-positions of the uracil resulted in potent compounds such as 24 (K-i = 0.45 nM). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.057
• 作为产物：
  描述：

  5-溴尿嘧啶 、 2-氟-6-(三氟甲基)溴苄 在 N,O-双三甲硅基乙酰胺 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 5-bromo-1-[2-fluoro-6-(trifluoromethyl)benzyl]pyrimidine-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 UTILISES COMME ANTAGONISTES DU RECEPTEUR D'HORMONE LIBERANT DE LA GONADOTROPHINE

  摘要：

  GnRH受体拮抗剂被披露，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R1a、R1b、R1c、R2a、R2b、R3、R4、R5、R6和X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的组合物，以及与在需要时对抗性腺激素释放激素的使用方法。

  公开号：

  WO2005007165A1

文献信息

• [EN] URACIL-TYPE GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS AND METHODS RELATED THERETO<br/>[FR] ANTAGONISTES DE TYPE URACIL GONADOLIBÉRINE ET LES MÉTHODES AFFÉRENTES
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2005113516A1

  公开（公告）日：2005-12-01

  Compounds having utility as GnRH receptor antagonists and for treatment of a variety of sex-hormone related conditions in both men and women. Such compounds have the following structure (I): (I) wherein R1a, R1b, R1c, R2a, R2b, R3, R4, R5, R6, R7, n and X are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of structure (I) 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.

  具有作为GnRH受体拮抗剂的效用，并用于治疗男性和女性的各种与性激素相关疾病的化合物。这些化合物具有以下结构（I）：（I）其中R1a、R1b、R1c、R2a、R2b、R3、R4、R5、R6、R7、n和X如本文所定义，包括立体异构体、前药和其药用可接受盐。还公开了含有结构（I）化合物的组合物，与药用可接受载体结合，以及与使用该组合物拮抗需要该物质的受试者中的促性腺激素释放激素相关的方法。
• [EN] GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS AND METHODS RELATING THERETO<br/>[FR] ANTAGONISTES DES RECEPTEURS DES HORMONES LIBERANT DES GONADOTROPINES ET PROCEDES CONNEXES
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2005007633A1

  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: wherein n, R1a, R1b, R1c, R2a, R2b, R3, R4, R5, R6 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.

  抑制性激素释放激素受体拮抗剂已经被披露，可用于治疗男性和女性的多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n、R1a、R1b、R1c、R2a、R2b、R3、R4、R5、R6和X如本文所定义，包括立体异构体、前药和其药用可接受的盐。还披露了含有本发明化合物的组合物，以及与药用可接受载体结合的方法，用于拮抗需要的受试者体内的促性腺激素释放激素。
• Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
  申请人：Guo Zhiqiang

  公开号：US20050038057A1

  公开（公告）日：2005-02-17

  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 1c , R 2a , R 2b , R 3 , R 4 , R 5 , R 6 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.

  本发明揭示了GnRH受体拮抗剂，可用于治疗男女性激素相关疾病的多种情况。本发明的化合物具有以下结构：其中R1a，R1b，R1c，R2a，R2b，R3，R4，R5，R6和X的定义如本文所述，包括立体异构体，前药和其药物可接受的盐。还揭示了含有本发明化合物的组合物及其与药物可接受的载体的组合物，以及与用于拮抗需要该类物质的受试者的促性腺激素释放激素相关的方法。
• Uracil-Type Gonadotropin-Releasing Hormone Receptor Antagonists and Methods Related Thereto
  申请人：Zhu Yun-Fei

  公开号：US20080262005A1

  公开（公告）日：2008-10-23

  Compounds having utility as GnRH receptor antagonists and for treatment of a variety of sex-hormone related conditions in both men and women. Such compounds have the following structure (I): (I) wherein R 1a , R 1b , R 1c , R 2a , R 2b , R 3 , R 4 , R 5 , R 6 , R 7 , n and X are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of structure (I) 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.

  具有GnRH受体拮抗剂实用性的化合物，用于治疗男性和女性的多种性激素相关疾病。这些化合物具有以下结构（I）：（I）其中R1a，R1b，R1c，R2a，R2b，R3，R4，R5，R6，R7，n和X如此定义，包括立体异构体，前药和其药物学上可接受的盐。还披露了含有结构（I）的化合物和药学上可接受的载体的组合物，以及与使用其在需要拮抗促性腺激素释放激素的受试者相关的方法。
• GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS AND METHODS RELATING THERETO
  申请人：Guo Zhiqiang

  公开号：US20070191403A1

  公开（公告）日：2007-08-16

  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 1c , R 2a , R 2b , R 3 , R 4 , R 5 , R 6 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.

  本发明公开了具有治疗男女性激素相关疾病的效用的GnRH受体拮抗剂。本发明的化合物具有以下结构：其中，R1a、R1b、R1c、R2a、R2b、R3、R4、R5、R6和X的定义如本文所述，包括立体异构体、前药和其药物可接受的盐。本发明还公开了含有本发明化合物与药物可接受载体结合的组合物，以及与拮抗需要拮抗性腺激素释放激素的受试者相关的使用方法。