4-(tert-butyl)-N-(6-ethoxy-5-(2-methoxyphenoxy)-[2,2’-bipyrimidin]-4-yl)benzenesulfonamide

• 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: 4-(tert-butyl)-N-(6-ethoxy-5-(2-methoxyphenoxy)-[2,2’-bipyrimidin]-4-yl)benzenesulfonamide
• 英文别名: 4-tert-butyl-N-[6-ethoxy-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl]benzenesulphonamide；4-tert-butyl-N-[6-ethoxy-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide
• 化学式: C₂₇H₂₉N₅O₅S
• 分子量: 535.624
• InChiKey: OPEHFGGLLNIJFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  134
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-(2-甲氧基苯氧基)丙二酸二甲酯 在 正丁基锂 、 五氯化磷 、 sodium methylate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 乙腈 为溶剂， 反应 61.75h， 生成 4-(tert-butyl)-N-(6-ethoxy-5-(2-methoxyphenoxy)-[2,2’-bipyrimidin]-4-yl)benzenesulfonamide
  参考文献：
  名称：

  Metabolism study and biological evaluation of bosentan derivatives

  摘要：

  Bosentan, the first-in-class drug used in treatment of pulmonary arterial hypertension, is principally metabolized by the cytochromes P450, and it is responsible for cytochromes induction and drug-drug interaction events with moderate to severe consequences. A strategy to reduce drug-drug interactions consists of increasing the metabolic stability of the perpetrator, and fluorinated analogues are often designed to block the major sites of metabolism. In this paper bosentan analogues were synthesized, and their metabolism and biological activity were evaluated. All synthesized compounds showed an improved metabolic stability towards CYP2C9, with one maintaining a moderate antagonist effect towards the ETA receptor. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.06.006

文献信息

• Neue Sulfonamide
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0601386A1

  公开（公告）日：1994-06-15

  Die neuen Verbindungen der Formel worin R¹-R⁸, X, Y und n die in der Beschreibung angegebene Bedeutung haben, sind Hemmstoffe der Endothelin-Rezeptoren und können zur Behandlung von Erkrankungen verwendet werden, die mit die Vasokonstriktion erhöhenden Vorgängen assoziiert sind.

  新化合物的化学式为 其中 R¹-R⁸、X、Y 和 n 具有说明中给出的含义，是内皮素受体的抑制剂，可用于治疗与血管收缩增加过程相关的疾病。
• US5420129A
  申请人：——

  公开号：US5420129A

  公开（公告）日：1995-05-30
• [EN] PHARMACEUTICAL AND VETERINARY USES OF ENDOTHELIN ANTAGONISTS<br/>[FR] UTILISATIONS PHARMACEUTIQUES ET VETERINAIRES D'ANTAGONISTES DE L'ENDOTHELINE ET APPLICATIONS ASSOCIEES
  申请人：TEXAS BIOTECHNOLOGY CORP

  公开号：WO2001049289A1

  公开（公告）日：2001-07-12

  Pharmaceutical and veterinary uses of endothelin antagonists are provided. In particular, methods of treatment of laminitis, such as equine and bovine laminitis, by administration of one or more endothelin antagonists are provided. Methods of treatment, prevention, or amelioration of one or more symptoms of menopause; osteoporosis and metabolic bone disorders; climacteric disorders including hot flushes or flashes, abnormal clotting patterns, urogenital discomfort and increased incidence of cardiovascular disease, and other disorders associated with the reduction in ovarian function in women; pre-eclampsia; and control and management of labor during pregnancy by administration of endothelin antagonists are also provided.
• Metabolism study and biological evaluation of bosentan derivatives
  作者：Susan Lepri、Laura Goracci、Aurora Valeri、Gabriele Cruciani

  DOI：10.1016/j.ejmech.2016.06.006

  日期：2016.10

  Bosentan, the first-in-class drug used in treatment of pulmonary arterial hypertension, is principally metabolized by the cytochromes P450, and it is responsible for cytochromes induction and drug-drug interaction events with moderate to severe consequences. A strategy to reduce drug-drug interactions consists of increasing the metabolic stability of the perpetrator, and fluorinated analogues are often designed to block the major sites of metabolism. In this paper bosentan analogues were synthesized, and their metabolism and biological activity were evaluated. All synthesized compounds showed an improved metabolic stability towards CYP2C9, with one maintaining a moderate antagonist effect towards the ETA receptor. (C) 2016 Elsevier Masson SAS. All rights reserved.