3-[2(R)-amino-2-phenylethyl]-5-(2-chloro-3-methoxyphenyl)-1-[2,6-difluorobenzyl]pyrimidine-2,4-(1H,3H)-dione | 855230-34-1

• 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)-amino-2-phenylethyl]-5-(2-chloro-3-methoxyphenyl)-1-[2,6-difluorobenzyl]pyrimidine-2,4-(1H,3H)-dione
• 英文别名: 3-[2(R)-amino-2-phenylethyl]-5-(2-chloro-3-methoxyphenyl)-1-[2,6-difluorobenzyl]pyrimidine-2,4(1H,3H)-dione；3-((R)-2-Amino-2-phenyl-ethyl)-5-(2-chloro-3-methoxy-phenyl)-1-(2,6-difluoro-benzyl)-1H-pyrimidine-2,4-dione；3-[(2R)-2-amino-2-phenylethyl]-5-(2-chloro-3-methoxyphenyl)-1-[(2,6-difluorophenyl)methyl]pyrimidine-2,4-dione
• CAS: 855230-34-1
• 化学式: C₂₆H₂₂ClF₂N₃O₃
• 分子量: 497.929
• InChiKey: JIQRGFZMYYMAHF-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  75.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[2(R)-amino-2-phenylethyl]-5-(2-chloro-3-methoxyphenyl)-1-[2,6-difluorobenzyl]pyrimidine-2,4-(1H,3H)-dione 、 4-溴丁腈 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以95.5%的产率得到3-[2(R)-{[3-cyanopropyl]-amino}-2-phenylethyl]-5-(2-chloro-3-methoxyphenyl)-1-[2,6-difluorobenzyl]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
• 作为产物：
  描述：

  tert-butyl N-[(1R)-2-[5-bromo-3-[(2,6-difluorophenyl)methyl]-2,6-dioxopyrimidin-1-yl]-1-phenylethyl]carbamate 在 四(三苯基膦)钯 、 sodium carbonate 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 3-[2(R)-amino-2-phenylethyl]-5-(2-chloro-3-methoxyphenyl)-1-[2,6-difluorobenzyl]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

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。
• Uracils as potent antagonists of the human gonadotropin-releasing hormone receptor without atropisomers
  作者：Zhiqiang Guo、Yongsheng Chen、Charles Q. Huang、Timothy D. Gross、Joseph Pontillo、Martin W. Rowbottom、John Saunders、Scott Struthers、Fabio C. Tucci、Qiu Xie、Warren Wade、Yun-Fei Zhu、Dongpei Wu、Chen Chen

  DOI：10.1016/j.bmcl.2005.03.057

  日期：2005.5

  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.