4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(3-methoxy-phenoxy)-4-pyrimidinyl]-benzenesulphonamide | 150727-21-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(3-methoxy-phenoxy)-4-pyrimidinyl]-benzenesulphonamide
• 英文别名: Ro-46,2005；p-t-butyl-N-[6-(2-hydroxyethoxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]benzenesulfonamide；4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide
• CAS: 150727-21-2
• 化学式: C₂₃H₂₇N₃O₆S
• 分子量: 473.55
• InChiKey: KPJXDJRWFUDSEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-溴-2-氯嘧啶 、 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(3-methoxy-phenoxy)-4-pyrimidinyl]-benzenesulphonamide 在 sodium hydride 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 48.0h， 生成 N-[6-[2-(5-Bromo-pyrimidin-2-yloxy)-ethoxy]-5-(2-methoxy-phenoxy)-pyrimidin-4-yl]-4-tert-butyl-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
• 作为产物：
  描述：

  sodium glycolate 、 4-tert-butyl-N-[6-chloro-5-(o-methoxyphenoxy)-4-pyrimidinyl]-benzene sulfonamide 在 sodium 作用下， 以 乙二醇 为溶剂， 生成 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(3-methoxy-phenoxy)-4-pyrimidinyl]-benzenesulphonamide
  参考文献：
  名称：

  Sulfonamides

  摘要：

  化学式I的新磺胺类化合物，##STR1## 其中符号R.sup.1 -R.sup.9，R.sup.a，R.sup.b，X，Y和n的含义如描述中所示，以及其盐可用于治疗循环系统疾病，特别是高血压、缺血、血管痉挛和心绞痛。

  公开号：

  US05292740A1

文献信息

• Sulfonamide, ihre Herstellung und Verwendung als Heilmittel und Zwischenprodukte
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0526708B1

  公开（公告）日：2000-10-18
• US5292740A
  申请人：——

  公开号：US5292740A

  公开（公告）日：1994-03-08
• Potent and Selective ET-A Antagonists. 1. Syntheses and Structure−Activity Relationships of <i>N</i>-(6-(2-(Aryloxy)ethoxy)-4-pyrimidinyl)sulfonamide Derivatives
  作者：Hiroshi Morimoto、Hideshi Shimadzu、Emi Kushiyama、Hiroyuki Kawanishi、Toshihiro Hosaka、Yasushi Kawase、Kosuke Yasuda、Kohei Kikkawa、Rikako Yamauchi-Kohno、Koichiro Yamada

  DOI：10.1021/jm0102304

  日期：2001.10.1

  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.
• Sulfonamides
  申请人：Hoffmann-La Roche Inc.

  公开号：US05292740A1

  公开（公告）日：1994-03-08

  The novel sulfonamides of formula I, ##STR1## in which the symbols R.sup.1 -R.sup.9, R.sup.a, R.sup.b, X, Y and n have the significance given in the description and salts thereof can be used for the treatment of circulatory disorders, especially hypertension, ischemia, vasopasms and angina pectoris.

  化学式I的新磺胺类化合物，##STR1## 其中符号R.sup.1 -R.sup.9，R.sup.a，R.sup.b，X，Y和n的含义如描述中所示，以及其盐可用于治疗循环系统疾病，特别是高血压、缺血、血管痉挛和心绞痛。