4-hydrazinobenzamidine dihydrochloride | 99669-48-4

• 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-hydrazinobenzamidine dihydrochloride
• 英文别名: 4-Hydrazino-benzamidin; Dihydrochlorid；4-Hydrazinylbenzenecarboximidamide;hydrochloride
• CAS: 99669-48-4
• 化学式: C₇H₁₀N₄*2ClH
• 分子量: 223.105
• InChiKey: SOQBKMPPIRUQPS-UHFFFAOYSA-N

物化性质

• 熔点：
  269-270 °C (decomp)

计算性质

• 辛醇/水分配系数(LogP)：
  0.68
• 重原子数：
  12.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87.92
• 氢给体数：
  4.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4-hydrazinobenzamidine dihydrochloride 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 6.5h， 生成 2-(5-Bromo-2-hydroxy-biphenyl-3-yl)-1H-indole-5-carboxamidine
  参考文献：
  名称：

  Development of Serine Protease Inhibitors Displaying a Multicentered Short (<2.3 Å) Hydrogen Bond Binding Mode:  Inhibitors of Urokinase-Type Plasminogen Activator and Factor Xa

  摘要：

  Novel scaffolds that bind to serine proteases through a unique network of short hydrogen bonds to the catalytic Ser195 have been developed. The resulting potent serine protease inhibitors were designed from lead molecule 2-(2-hydroxyphenyl)1H-benzoimidazole-5-carboxamidine, 6b, which is known to display several modes of binding. For instance, 6b can recruit zinc and bind in a manner similar to that reported by bis(5-amidino-2-benzimidazolyl)methane (BABIM) (Nature 1998, 391, 608-612).(1) Alternatively, 6b can bind in the absence of zinc through a multicentered network of short (<2.3 Angstrom) hydrogen bonds. The lead structure was optimized in the zinc-independent binding mode toward a panel of six human serine proteases to yield optimized inhibitors such as 2-(3-bromo-2-hydroxy-5-methylphenyl)-1H-indole-5-carboxamidine, 22a, and 2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-carboxamidine, 22f. Structure-activity relationships determined that, apart from the amidine function, an indole or benzimidazole and an ortho substituted phenol group were also essential components for optimal potency. The affinities (K-i) of 22a and 22f, for example, bearing these groups ranged from 8 to 600 nM toward a panel of six human serine proteases. High-resolution crystal structures revealed that the binding mode of these molecules in several of the enzymes was identical to that of 6b and involved short (<2.3 Angstrom) hydrogen bonds among the inhibitor hydroxyl oxygen, Ser195, and a water molecule trapped in the oxyanion hole. In summation, novel and potent trypsin-like serine protease inhibitors possessing a unique mode of binding have been discovered.

  DOI：

  10.1021/jm0100638
• 作为产物：
  描述：

  4-aminobenzamidine dihydrochloride 在 盐酸 、 sodium nitrite 、 tin(ll) chloride 作用下， 以 水 为溶剂， 以100 %的产率得到4-hydrazinobenzamidine dihydrochloride
  参考文献：
  名称：

  Exploring Photoswitchable Binding Interactions with Small‐Molecule‐ and Peptide‐Based Inhibitors of Trypsin

  摘要：

  摘要要想在需要的时间和地点以光化学方式激活药物，就必须优化每种异构体状态之间的生物活性差异。作为实现这一目标的一个步骤，我们报告了对同一种蛋白酶--胰蛋白酶的小分子和多肽抑制剂，以更好地了解光开关药物如何与其生物靶标相互作用。最好的多肽抑制剂在同分异构状态之间的抑制活性相差五倍以上，而最好的小分子抑制剂仅相差 3.4 倍。对接和分子建模表明，这一结果是由于多肽抑制剂的关键结合残基在异构化时发生了巨大的三维结构变化；而小分子抑制剂则没有观察到这种变化。因此，我们证明了关键结合基团在辐照时发生的重大结构变化对于最大限度地提高异构态之间的生物活性差异至关重要。这是设计未来临床应用的光开关药物的一个重要考虑因素。

  DOI：

  10.1002/cbic.202300453

文献信息

• Bis-hydrazones
  申请人：HOECHST AG

  公开号：US02655538A1

  公开（公告）日：1953-10-13
• DE871891
  申请人：——

  公开号：——

  公开（公告）日：——