N-(3,5-diamino-6-chloropyrazine-2-carbonyl)-N''-[4-(4-hydroxyphenyl)butyl]-guanidine

• 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: N-(3,5-diamino-6-chloropyrazine-2-carbonyl)-N''-[4-(4-hydroxyphenyl)butyl]-guanidine
• 英文别名: 3,5-diamino-6-chloro-N-[N'-[4-(4-hydroxyphenyl)butyl]carbamimidoyl]pyrazine-2-carboxamide
• 化学式: C₁₆H₂₀ClN₇O₂
• 分子量: 377.834
• InChiKey: WSIQWEOUTVWPPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  166
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-(4-Methoxyphenyl)butylazide 在 水 、 氢溴酸 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 N-(3,5-diamino-6-chloropyrazine-2-carbonyl)-N''-[4-(4-hydroxyphenyl)butyl]-guanidine
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of Novel 2-Substituted Pyrazinoylguanidine Epithelial Sodium Channel Blockers:  Drugs for Cystic Fibrosis and Chronic Bronchitis

  摘要：

  Amiloride (1), the prototypical epithelial sodium channel (ENaC) blocker, has been administered with limited success as aerosol therapy for improving pulmonary function in patients with the genetic disorder cystic fibrosis. This study was conducted to synthesize and identify more potent, less reversible ENaC blockers, targeted for aerosol therapy and possessing minimal systemic renal activity. A series of novel 2-substituted acylguanidine analogues of amiloride were synthesized and evaluated for potency and reversibility on bronchial ENaC. All compounds tested were more potent and less reversible at blocking sodium-dependent shortcircuit current than amiloride. Compounds 30-34 showed the greatest potency on ENaC with IC50 values below 10 nM. A regioselective difference in potency was found (compounds 30, 39, and 40), whereas no stereospecific (compounds 33, 34) difference in potency on ENaC was displayed. Lead compound 32 was 102-fold more potent and 5-fold less reversible than amiloride and displayed the lowest IC50 value ever reported for an ENaC blocker.

  DOI：

  10.1021/jm051134w

文献信息

• METHODS OF USING SODIUM CHANNEL BLOCKERS
  申请人：Johnson R. Michael

  公开号：US20070265280A1

  公开（公告）日：2007-11-15

  The present invention relates to use of a compound represented by formula (I): in which at least one of R 3 and R 4 is a group represented by formula (A): where the structural variables are as defined herein. The compounds are useful for blocking sodium channels and treating a variety of conditions.

  本发明涉及使用式（I）所表示的化合物： 其中R3和R4中至少有一个是由式（A）所表示的基团： 其中结构变量如本文所定义。该化合物可用于阻断钠通道并治疗多种疾病。
• CAPPED PYRAZINOYLGUANIDINE SODIUM CHANNEL BLOCKERS
  申请人：JOHNSON Michael R.

  公开号：US20080167466A1

  公开（公告）日：2008-07-10

  The present invention relates to sodium channel blockers. The present invention also includes a variety of methods of treatment using these inventive sodium channel blockers.

  本发明涉及钠通道阻滞剂。本发明还包括使用这些创新的钠通道阻滞剂的各种治疗方法。
• SOLUBLE AMIDE & ESTER PYRAZINOYLGUANIDINE SODIUM CHANNEL BLOCKERS
  申请人：JOHNSON Michael R.

  公开号：US20080171879A1

  公开（公告）日：2008-07-17

  The present invention relates to sodium channel blockers. The present invention also includes a variety of methods of treatment using these inventive sodium channel blockers.

  本发明涉及钠通道阻滞剂。本发明还包括使用这些创新的钠通道阻滞剂的各种治疗方法。
• SODIUM CHANNEL BLOCKERS
  申请人：Parion Sciences, Inc.

  公开号：EP1485359B1

  公开（公告）日：2007-12-05
• PYRAZINOYLGUANIDINE COMPOUNDS FOR USE AS TASTE MODULATORS
  申请人：JOHNSON Michael R.

  公开号：US20080249109A1

  公开（公告）日：2008-10-09

  The present invention relates to blocking salt taste using compounds of Formula I as defined herein.