(E)-N-[6-chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-(pyridin-2-yl)ethenesulfonamide | 403604-75-1

• 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: (E)-N-[6-chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-(pyridin-2-yl)ethenesulfonamide
• CAS: 403604-75-1
• 化学式: C₂₂H₁₇ClN₆O₄S
• 分子量: 496.934
• InChiKey: ZWTQCYLQPHUURS-GXDHUFHOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  34.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  129.08
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  sodium methylate 、 (E)-N-[6-chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-(pyridin-2-yl)ethenesulfonamide 以 甲醇 为溶剂， 以79%的产率得到(E)-2-Pyridin-2-yl-ethenesulfonic acid [6-methoxy-5-(2-methoxy-phenoxy)-[2,2']bipyrimidinyl-4-yl]-amide
  参考文献：
  名称：

  Ethenesulfonamide and ethanesulfonamide derivatives, a novel class of orally active endothelin-A receptor antagonists

  摘要：

  In the previous paper, we described a series of 2-phenylethenesulfonamide derivatives, a novel class of ET(A)-selective endothelin (ET) receptor antagonists, including the 2-methoxyethoxy derivative 2a and the 2-fluoroethoxy derivative (2b). In this paper, we wish to report further details of structure-activity relationships (SARs) of the two regions of the molecule in compound 2b, which were the alkoxy region at the 6-position of the core pyrimidine ring and the 2-phenylethenesulfonamide region. In these modifications, replacement of the 2-fluoroethoxy group with a methoxy group (6e) and replacement of the 2-phenylethenesulfonamide group with a 2-(pyridin-3-yl)ethenesulfonamide group (61) or 2-phenylethanesulfonamide group (6q) were well tolerated both in the ET(A) binding affinity and ET(A) selectivity. Among them, compound 6e showed further improvement in oral activity compared to 2b. After oral administration, compound 6e inhibited the big ET-1 induced pressor response in conscious rats at 0.3 mg/kg with a duration of >6.5 h. Compound 6e also exhibited a potent antagonistic activity in the pithed rats. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00187-0
• 作为产物：
  描述：

  4,6-二羟基-5-(2-甲氧基苯氧基)-2-(2-嘧啶基)嘧啶 在 2,4,6-三甲基嘧啶 、 sodium hydride 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.67h， 生成 (E)-N-[6-chloro-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]-2-(pyridin-2-yl)ethenesulfonamide
  参考文献：
  名称：

  Ethenesulfonamide and ethanesulfonamide derivatives, a novel class of orally active endothelin-A receptor antagonists

  摘要：

  In the previous paper, we described a series of 2-phenylethenesulfonamide derivatives, a novel class of ET(A)-selective endothelin (ET) receptor antagonists, including the 2-methoxyethoxy derivative 2a and the 2-fluoroethoxy derivative (2b). In this paper, we wish to report further details of structure-activity relationships (SARs) of the two regions of the molecule in compound 2b, which were the alkoxy region at the 6-position of the core pyrimidine ring and the 2-phenylethenesulfonamide region. In these modifications, replacement of the 2-fluoroethoxy group with a methoxy group (6e) and replacement of the 2-phenylethenesulfonamide group with a 2-(pyridin-3-yl)ethenesulfonamide group (61) or 2-phenylethanesulfonamide group (6q) were well tolerated both in the ET(A) binding affinity and ET(A) selectivity. Among them, compound 6e showed further improvement in oral activity compared to 2b. After oral administration, compound 6e inhibited the big ET-1 induced pressor response in conscious rats at 0.3 mg/kg with a duration of >6.5 h. Compound 6e also exhibited a potent antagonistic activity in the pithed rats. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00187-0