4-tert-butyl-N-(2-(4-methylphenyl)phenyl)-3-(2-((5-(3-thienyl-2-pyrimidinyl)oxy)ethoxy)phenyl)benzenesulfonamide

• 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: 4-tert-butyl-N-(2-(4-methylphenyl)phenyl)-3-(2-((5-(3-thienyl-2-pyrimidinyl)oxy)ethoxy)phenyl)benzenesulfonamide
• 英文别名: 4-tert-butyl-N-[2-(4-methylphenyl)-3-[2-(5-thiophen-3-ylpyrimidin-2-yl)oxyethoxy]phenyl]benzenesulfonamide
• 化学式: C₃₃H₃₃N₃O₄S₂
• 分子量: 599.775
• InChiKey: LVIKLZBRGSDUER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  对叔丁基苯磺酰氯 在 10percent Pd/C 吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 水 、 氢气 、 sodium hydride 作用下， 以 1,4-二氧六环 、 乙醇 、 N,N-二甲基乙酰胺 为溶剂， 反应 30.33h， 生成 4-tert-butyl-N-(2-(4-methylphenyl)phenyl)-3-(2-((5-(3-thienyl-2-pyrimidinyl)oxy)ethoxy)phenyl)benzenesulfonamide
  参考文献：
  名称：

  Potent and Selective ET-A Antagonists. 1. Syntheses and Structure−Activity Relationships of N-(6-(2-(Aryloxy)ethoxy)-4-pyrimidinyl)sulfonamide Derivatives

  摘要：

  Modifications to the ETA/B mixed type compounds 1 (Ro. 46-2005) and 2 (bosentan) were performed. Introduction of a pyrimidine group into 1 resulted in a dramatic increase in affinity for the ETA receptor, and the subsequent optimization of substituents on the pyrimidine ring led us to the discovery of N-(6-(2-((5-bromo-2-pyrimidinyl)oxy)ethoxy)-5-(4-methylphenyl)-4pyrimidinyl)-4-tert-butylbenzenesulfonamide (7k), which showed an extremely high affinity for the human cloned ETA receptor (K-i = 0.0042 +/-0.0038 nM) and an ETA/B receptor selectivity up to 29 000 (K-i = 130 +/- 50 nM for the human cloned ETB receptor). The compound was designed on the hypothesis that the hydrogen atom of the hydroxyl group in 1 and 2 played a role not as a proton donor but as an acceptor in the possible hydrogen bonding with Tyr129. Since the incorporation of a pyrimidinyl group into the hydroxyethoxy side chain of the nonselective antagonist (1) dramatically enhanced both the ETA receptor affinity and selectivity, and since similar results were obtained from the benzene analogues, we put forward the hypothesis that a "pyrimidine binding pocket" might exist in the ETA receptor.

  DOI：

  10.1021/jm0102304