3-(3-amino-1,2,4-oxadiazol-5-yl)-5-chloro-2,6-pyrazinediamine | 73631-29-5

• 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: 3-(3-amino-1,2,4-oxadiazol-5-yl)-5-chloro-2,6-pyrazinediamine
• 英文别名: 3-amino-5-[3,5-diamino-6-chloropyrazin-2-yl]-1,2,4-oxadiazole；3-(3-amino-1,2,4-oxadiazol-5-yl)-5-chloropyrazine-2,6-diamine
• CAS: 73631-29-5
• 化学式: C₆H₆ClN₇O
• 分子量: 227.613
• InChiKey: GJLPISUGPIFCFQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  143
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-(3-amino-1,2,4-oxadiazol-5-yl)-5-chloro-2,6-pyrazinediamine 生成 脒氯嗪
  参考文献：
  名称：

  BOCK M. G.; SMITH R. L.; BLAINE E. H.; CRAGOE E. J., JR., J. MED. CHEM., 29,(1986) N 8, 1540-1544

  摘要：

  DOI：
• 作为产物：
  描述：

  3,5-二氨基-6-氯-2-吡嗪甲腈 在 盐酸 、 盐酸羟胺 、 potassium carbonate 作用下， 以 吡啶 、 甲醇 为溶剂， 反应 126.33h， 生成 3-(3-amino-1,2,4-oxadiazol-5-yl)-5-chloro-2,6-pyrazinediamine
  参考文献：
  名称：

  Synthesis and diuretic profile of 3-(3-amino-1,2,4-oxadiazol-5-yl)-5-chloro-2,6-pyrazinediamine, an amiloride-type diuretic

  摘要：

  The synthesis of an analogue of amiloride in which the acylguanidine moiety has been replaced by a 1,2,4-oxadiazol-3-amine unit is described. This substance (3, CGS 4270) exhibited a diuretic profile similar to that of amiloride when evaluated in the rat and the dog. In the rat, combination with hydrochlorothiazide increased diuresis and saluresis and returned potassium levels to control values. A series of 5-aryl-1,2,4-oxadiazol-3-amines not directly related to amiloride was prepared, but these substances had no diuretic activity.

  DOI：

  10.1021/jm00180a025

文献信息

• Zur Farbreaktion von Amiloridhydrochlorid Ph. Eur.
  作者：Klaus Görlitzerl、Silke Huth、Peter Jones、Edith Gößnitzer、Winfried Wendelin

  DOI：10.3797/scipharm.aut-01-199

  日期：——

  The reaction of amiloride hydrochloride (1·HCl) with bromine in alkaline solution generated a yellow-brown dehydrogenation product, which turned out as 3-(3-amino-1,2,4-oxadiazol-5-yl)-5-chloro-2,6-pyrazinediamine (2). The structure was deduced from the MS and the NMR spectra of 2 with the help of comparisons with corresponding spectra of amiloride (1) and reference substances 3 - 5. The agreement

  盐酸阿米洛利（1·HCl）与溴在碱性溶液中反应，生成黄棕色脱氢产物，生成3-（3-氨基-1,2,4-恶二唑-5-基）-5-氯-2,6-吡嗪二胺（2）。根据与阿米洛利（1）和参考物质3-5的相应光谱进行比较，由MS和2的NMR光谱推导其结构。该产品与真实的恶二唑基吡嗪2的所有相关数据以及完成的X射线分析证实了假定的结构。还讨论了2的形成机理。
• Novel substituted pyrazinyl-1,2,4-oxadiazoles, processes for preparing the same and a pharmaceutical composition containing the same
  申请人：Merck & Co., Inc.

  公开号：EP0040422A1

  公开（公告）日：1981-11-25

  Novel substituted pyrazinyl-1,2,4-oxadiazoles of the formulas are disclosed wherein R is hydrogen or lower alkyl (C1-5), R1 is hydrogen or lower alkyl (C1-5), R2 is hydrogen or lower alkyl (C1-5), R3 is hydrogen or lower alkyl (C1-5), R and R' can be joined to form an alkylene group of from 2-4 i carbon atoms, R4 is lower alkyl (C1-5) X is halo, cyano or phenyl, and Y- is chloride, bromide or iodide, or a suitable anion. Processing for preparing the same are also described. The compounds are useful in the treatment of edema and hypertension.

  新颖的取代吡嗪基-1,2,4-恶二唑，其式如下 的新型取代吡嗪基-1,2,4-恶二唑 R 是氢或低级烷基 (C1-5)、 R1 是氢或低级烷基 (C1-5) R2 是氢或低级烷基 (C1-5) R3 是氢或低级烷基（C1-5）、 R 和 R' 可以连接成一个含有 2-4 i 个碳原子的亚烷基、 R4 是低级烷基（C1-5） X 是卤代、氰基或苯基，以及 Y- 是氯化物、溴化物或碘化物，或合适的阴离子。 此外，还介绍了制备方法。这些化合物可用于治疗水肿和高血压。
• Synthesis and preliminary evaluation of amiloride analogs as inhibitors of the urokinase-type plasminogen activator (uPA)
  作者：Hayden Matthews、Marie Ranson、Joel D.A. Tyndall、Michael J. Kelso

  DOI：10.1016/j.bmcl.2011.09.044

  日期：2011.11

  A known side-activity of the oral potassium-sparing diuretic drug amiloride is inhibition of the enzyme urokinase-type plasminogen activator (uPA, K-i = 7 mu M), a promising anticancer target. Several studies have demonstrated significant antitumor/metastasis properties for amiloride in animal cancer models and it would appear that these arise, at least in part, through inhibition of uPA. Selective optimization of amiloride's structure for more potent inhibition of uPA and loss of diuretic effects would thus appear as an attractive strategy towards novel anticancer agents. The following report is a preliminary structure-activity exploration of amiloride analogs as inhibitors of uPA. A key finding was that the well-studied 5-substituted analogs ethylisopropyl amiloride (EIPA) and hexamethylene amiloride (HMA) are approximately twofold more potent than amiloride as uPA inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.
• WATTHEY J. W. H.; DESAI M.; RUTLEDGE R.; DOTSON R., J. MED. CHEM., 1980, 23, NO 6, 690-692
  作者：WATTHEY J. W. H.、 DESAI M.、 RUTLEDGE R.、 DOTSON R.

  DOI：——

  日期：——
• Synthesis and biological activity of 3-amino-5-(3,5-diamino-6-chloropyrazin-2-yl)-1,2,4-oxadiazole. An amiloride prodrug
  作者：Mark G. Bock、Robert L. Smith、Edward H. Blaine、Edward J. Cragoe

  DOI：10.1021/jm00158a040

  日期：1986.8

  The pyrazinyl-1,2,4-oxadiazoles 4a and 4b were synthesized by two different approaches. The corresponding N-methyloxadiazolium salts 13a and 13b were also prepared. These compounds were evaluated for their diuretic and saluretic activity in rats and dogs. All compounds exhibited electrolyte excretion profiles similar to amiloride 1. The facile conversion of 4a to 1 was demonstrated chemically and in vivo in both rats and dogs.