5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-methylsulfonylbenzyl]-3-{3-(1-piperazinyl)-2(R)-phenylpropyl}-6-methylpyrimidine-2,4(1H,3H)-dione

• 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-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-methylsulfonylbenzyl]-3-{3-(1-piperazinyl)-2(R)-phenylpropyl}-6-methylpyrimidine-2,4(1H,3H)-dione
• 英文别名: 5-(2-fluoro-3-methoxyphenyl)-l-[2-fluoro-6-methylsulfonylbenzyl]-3-{3-(1-piperazinyl)-2(R)-phenylpropyl}-6-methylpyrimidine-2,4(1H,3H)-dione；5-(2-fluoro-3-methoxyphenyl)-1-[(2-fluoro-6-methylsulfonylphenyl)methyl]-6-methyl-3-[(2R)-2-phenyl-3-piperazin-1-ylpropyl]pyrimidine-2,4-dione
• 化学式: C₃₃H₃₆F₂N₄O₅S
• 分子量: 638.735
• InChiKey: YIGVYDQTUAXHOW-XMMPIXPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  45
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-methylsulfonylbenzyl]-3-{2(R)-phenylpropyl-3-one}-6-methylpyrimidine-2,4(1H,3H)-dione 、 N-Boc-哌嗪 在 三乙酰氧基硼氢化钠 、 三氟乙酸 作用下， 以 1,1-二氯乙烷 、 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 为溶剂， 反应 2.0h， 以85%的产率得到5-(2-fluoro-3-methoxyphenyl)-1-[2-fluoro-6-methylsulfonylbenzyl]-3-{3-(1-piperazinyl)-2(R)-phenylpropyl}-6-methylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  [EN] GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS AND METHODS RELATING THERETO
  [FR] ANTAGONISTES DES RECEPTEURS DES HORMONES LIBERANT DES GONADOTROPINES ET PROCEDES CONNEXES

  摘要：

  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。

  公开号：

  WO2005007633A1

文献信息

• Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
  申请人：Huang Q. Charles

  公开号：US20060122204A1

  公开（公告）日：2006-06-08

  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, 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，其在男性和女性的多种性激素相关疾病治疗中具有用途。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，前药和其药学上可接受的盐。还揭示了含有本发明化合物与药学上可接受的载体结合的组合物，以及与其相关的方法，用于拮抗需要此类物质的受体释放性激素。
• AQUEOUS DISPERSION MIXTURE
  申请人：Sumitomo Chemical Company, Ltd.

  公开号：EP3296361A1

  公开（公告）日：2018-03-21

  The present invention provides an aqueous dispersion mixture comprising; an aqueous dispersion (A) that comprises a crystalline polyolefin (a) as a dispersoid thereof; an aqueous dispersion (B) that comprises a crystalline polyurethane (b) as a dispersoid thereof; and an aqueous dispersion (C) that comprises a non-crystalline polyurethane (c) as a dispersoid thereof, wherein the crystalline polyolefin (a) is a non-chlorine modified polyolefin , wherein the crystalline polyurethane (b) has a crystal melting heat amount equal to or larger than 3 J/g measured by differential scanning calorimetry, wherein the non-crystalline polyurethane (c) has a crystal melting heat amount smaller than 3 J/g measured by differential scanning calorimetry, and wherein the aqueous dispersion (B) comprises a non-volatile content of 30 parts by mass to 100 parts by mass and the aqueous dispersion (C) comprises a non-volatile content of 20 parts by mass to 80 parts by mass, relative to a non-volatile content of 100 parts by mass of the aqueous dispersion (A).

  本发明提供了一种水性分散体混合物，该混合物包括：以结晶聚烯烃（a）为分散体的水性分散体（A）；以结晶聚氨酯（b）为分散体的水性分散体（B）；以及以非结晶聚氨酯（c）为分散体的水性分散体（C）；其中结晶聚烯烃 (a) 是一种非氯改性聚烯烃，其中结晶聚氨酯 (b) 通过差示扫描量热法测得的晶体熔热量等于或大于 3 J/g、其中，非结晶聚氨酯 (c) 的晶体熔化热量小于 3 J/g（通过差示扫描量热法测量）；相对于 100 份（质量）水性分散液 (A) 的非挥发性含量，水性分散液 (B) 的非挥发性含量为 30 份（质量）至 100 份（质量），水性分散液 (C) 的非挥发性含量为 20 份（质量）至 80 份（质量）。
• Aqueous dispersion mixture
  申请人：SUMITOMO CHEMICAL COMPANY, LIMITED

  公开号：US10344156B2

  公开（公告）日：2019-07-09

  The present invention provides an aqueous dispersion mixture comprising; an aqueous dispersion (A) that comprises a crystalline polyolefin (a) as a dispersoid thereof; an aqueous dispersion (B) that comprises a crystalline polyurethane (b) as a dispersoid thereof; and an aqueous dispersion (C) that comprises a non-crystalline polyurethane (c) as a dispersoid thereof, wherein the crystalline polyolefin (a) is a non-chlorine modified polyolefin, wherein the crystalline polyurethane (b) has a crystal melting heat amount equal to or larger than 3 J/g measured by differential scanning calorimetry, wherein the non-crystalline polyurethane (c) has a crystal melting heat amount smaller than 3 J/g measured by differential scanning calorimetry, and wherein the aqueous dispersion (B) comprises a non-volatile content of 30 parts by mass to 100 parts by mass and the aqueous dispersion (C) comprises a non-volatile content of 20 parts by mass to 80 parts by mass, relative to a non-volatile content of 100 parts by mass of the aqueous dispersion (A).

  本发明提供了一种水性分散体混合物，该混合物包括：以结晶聚烯烃（a）为分散体的水性分散体（A）；以结晶聚氨酯（b）为分散体的水性分散体（B）；以及以非结晶聚氨酯（c）为分散体的水性分散体（C）；其中结晶聚烯烃 (a) 是一种非氯改性聚烯烃，其中结晶聚氨酯 (b) 通过差示扫描量热法测量的晶体熔热量等于或大于 3 J/g、其中非结晶聚氨酯 (c) 的晶体熔化热量小于 3 焦耳/克（通过差示扫描量热法测量），并且相对于 100 份（质量）水性分散液 (A) 的非挥发性含量，水性分散液 (B) 的非挥发性含量为 30 份（质量）至 100 份（质量），水性分散液 (C) 的非挥发性含量为 20 份（质量）至 80 份（质量）。
• GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS AND METHODS RELATING THERETO
  申请人：NEUROCRINE BIOSCIENCES, INC.

  公开号：EP1644342A1

  公开（公告）日：2006-04-12
• 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