3-[2(R)-(tert-butoxycarbonylamino)-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-methylthiobenzyl]-6-methylpyrimidine-2,4(1H,3H)-dione | 830346-54-8

• 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: 3-[2(R)-(tert-butoxycarbonylamino)-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-methylthiobenzyl]-6-methylpyrimidine-2,4(1H,3H)-dione
• 英文别名: 3-[2(R)-tert-butoxvcarbonylamino-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-methylthiobenzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dione；tert-butyl N-[(1R)-2-[5-(2-fluoro-3-methoxyphenyl)-3-[(2-fluoro-6-methylsulfanylphenyl)methyl]-4-methyl-2,6-dioxopyrimidin-1-yl]-1-phenylethyl]carbamate
• CAS: 830346-54-8
• 化学式: C₃₃H₃₅F₂N₃O₅S
• 分子量: 623.721
• InChiKey: RRUDPWIJSZIAHB-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-[2(R)-(tert-butoxycarbonylamino)-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-methylthiobenzyl]-6-methylpyrimidine-2,4(1H,3H)-dione 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 以53%的产率得到3-[2(R)-(tert-butoxycarbonylamino)-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-methylsulfonylbenzyl]-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 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
• 作为产物：
  描述：

  3-[2(R)-(tert-butoxycarbonylamino)-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2,6-difluorobenzyl]-6-methylpyrimidine-2,4(1H,3H)-dione 、 sodium thiomethoxide 在 氮气 、 乙醚 、 水 、 碳酸氢钠 、 Brine 、 Sodium sulfate-III 、 crude product 、 silica gel 、 乙酸乙酯 、 正己烷 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 以to yield compound 5b as a pale yellow solid (27 g, 44 mmol, 78%)的产率得到3-[2(R)-(tert-butoxycarbonylamino)-2-phenylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-methylthiobenzyl]-6-methylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Gonadotropin-releasing hormone receptor antagonists and methods relating thereto

  摘要：

  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。

  公开号：

  US20050043338A1

文献信息

• [EN] PYRIMIDINE-2, 4-DIONE DERIVATIVES AS GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE PYRIMIDINE-2, 4-DIONE UTILISES COMME ANTAGONISTES DU RECEPTEUR D'HORMONE LIBERANT DE LA GONADOTROPHINE
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2005007165A1

  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 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.

  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。
• 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。
• 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。
• Arylpyrimidines useful for the treatment of sex hormone-related conditions such as endometriosis, prostate cancer and the like
  申请人：NEUROCRINE BIOSCIENCES, INC.

  公开号：EP1644342B1

  公开（公告）日：2012-05-09
• PYRIMIDINE-2,4-DIONE DERIVATIVES AS GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS
  申请人：NEUROCRINE BIOSCIENCES, INC.

  公开号：EP1646389B1

  公开（公告）日：2008-09-10