1-Ethyl-2-amino-guanidin | 55908-78-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-Ethyl-2-amino-guanidin
• 英文别名: N-Amino-N'-ethyl-guanidin；N-ethyl-N'-amino-guanidine；N-Aethyl-N'-amino-guanidin；1-amino-2-ethylguanidine
• CAS: 55908-78-6
• 化学式: C₃H₁₀N₄
• 分子量: 102.139
• InChiKey: VMENIQFAVOLAHN-UHFFFAOYSA-N

物化性质

• 熔点：
  >300 °C
• 沸点：
  149.2±23.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  7
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  76.4
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-Ethyl-2-amino-guanidin 在 盐酸 、 sodium nitrite 作用下， 生成 1-乙基-1H-四唑-5-胺
  参考文献：
  名称：

  Preparation and isomerization of 5-alkylaminotetrazoles

  摘要：

  DOI：

  10.1021/jo50013a002
• 作为产物：
  描述：

  2-乙基-1-硝基胍 在 溶剂黄146 、 铂 作用下， 生成 1-Ethyl-2-amino-guanidin
  参考文献：
  名称：

  Lieber; Smith, Journal of the American Chemical Society, 1937, vol. 59, p. 2288

  摘要：

  DOI：

文献信息

• Synthesis, Antileishmanial Activity and in silico Studies of Aminoguanidine Hydrazones (AGH) and Thiosemicarbazones (TSC) Against Leishmania chagasi Amastigotes
  作者：Thiago M. de Aquino、Paulo H. B. França、Érica E. E. S. Rodrigues、Igor. J.S. Nascimento、Paulo F. S. Santos-Júnior、Pedro G. V. Aquino、Mariana S. Santos、Aline C. Queiroz、Morgana V. Araújo、Magna S. Alexandre-Moreira、Raiza R. L. Rodrigues、Klinger A. F. Rodrigues、Johnnatan D. Freitas、Jacques Bricard、Mario R. Meneghetti、Jean-Jacques Bourguignon、Martine Schmitt、Edeildo F. da Silva-Júnior、João X. de Araújo-Júnior

  DOI：10.2174/1573406417666210216154428

  日期：2022.2

  Leishmaniasis is a worldwide health problem, highly endemic in developing countries. Among the four main clinical forms of the disease, visceral leishmaniasis is the most severe, fatal in 95% of cases. The undesired side-effects from first-line chemotherapy and the reported drug resistance search for effective drugs that can replace or supplement those currently used an urgent need. Aminoguanidine hydrazones (AGH's) have been explored for exhibiting a diverse spectrum of biological activities, in particular the antileishmanial activity of MGBG. The bioisosteres thiosemicarbazones (TSC's) offer a similar biological activity diversity, including antiprotozoal effects against Leishmania species and Trypanosoma cruzi.

  Considering the impact of leishmaniasis worldwide, this work aimed to design, synthesize, and perform a screening upon L. chagasi amastigotes and for the cytotoxicity of the small "in-house" library of both AGH and TSC derivatives and their structurally-related compounds.

  A set of AGH's (3-7), TSC's (9, 10), and semicarbazones (11) were initially synthesized. Subsequently, different semi-constrained analogs were designed and also prepared, including thiazolidines (12), dihydrothiazines (13), imidazolines (15), pyrimidines (16, 18) azines (19, 20), and benzotriazepinones (23-25). All intermediates and target compounds were obtained with satisfactory yields and exhibited spectral data consistent with their structures. All final compounds were evaluated against L. chagasi amastigotes and J774.A1 cell line. Molecular docking was performed towards trypanothione reductase using GOLD® software.

  The AGH's 3i, 4a, and 5d, and the TSC's 9i, 9k, and 9o were selected as valuable hits. These compounds presented antileishmanial activity compared with pentamidine, showing IC50 values ranged from 0.6 to 7.27 μM, maximal effects up to 55.3%, and satisfactory SI values (ranged from 11 to 87). On the other hand, most of the resulting semi-constrained analogs were found cytotoxic or presented reduced antileishmanial activity. In general, TSC class is more promising than its isosteric AGH analogs, and the beneficial aromatic substituent effects are not similar in both series. In silico studies have suggested that these hits are capable of inhibiting the trypanothione reductase from the amastigote forms.

  The promising antileishmanial activity of three AGH’s and three TSC’s was characterized. These compounds presented antileishmanial activity compared with PTD, showing IC50 values ranged from 0.6 to 7.27 μM, and satisfactory SI values. Further pharmacological assays involving other Leishmania strains are under progress, which will help to choose the best hits for in vivo experiments.

  背景：利什曼病是全球性健康问题，在发展中国家高度流行。在该病的四种主要临床形式中，内脏利什曼病是最严重的，95%的病例会致命。由于一线化疗药物的不良副作用和报道的药物耐药性，迫切需要寻找可以替代或补充当前使用的有效药物。氨基胍脒肼酮（AGH）已被探索用于展示多样的生物活性，特别是MGBG的抗利什曼病活性。生物同功异构体硫脲半胱氨酮（TSC）提供类似的生物活性多样性，包括对利什曼病和克氏锥虫的抗原虫效应。 目的：考虑到利什曼病在全球范围内的影响，本研究旨在设计、合成并对L. chagasi阿马斯蒂果虫进行筛选，以及对小型“内部”AGH和TSC衍生物及其结构相关化合物的细胞毒性进行评估。 方法：首先合成了一组AGH（3-7）、TSC（9, 10）和半胱氨酮（11）。随后，设计并制备了不同的半约束类似物，包括噻唑烷（12）、二氢噻嗪（13）、咪唑烷（15）、嘧啶（16, 18）、吲哚烷（19, 20）和苯并三唑环酮（23-25）。所有中间体和目标化合物均以满意的收率获得，并展示了与其结构一致的光谱数据。所有最终化合物均对L. chagasi阿马斯蒂果虫和J774.A1细胞系进行了评估。使用GOLD®软件对其进行了针对巯基还原酶的分子对接。 结果：AGH的3i、4a和5d以及TSC的9i、9k和9o被选为有价值的命中物。这些化合物与五环胺相比具有抗利什曼病活性，IC50值范围从0.6到7.27μM，最大效果高达55.3％，满意的SI值（范围从11到87）。另一方面，大多数结果的半约束类似物被发现具有细胞毒性或具有降低的抗利什曼病活性。总体而言，TSC类比其同功异构AGH类更有前景，而有益的芳香族取代作用在两个系列中并不相似。计算机模拟研究表明这些命中物能够抑制阿马斯蒂果虫的巯基还原酶。 结论：三种AGH和三种TSC的有前景的抗利什曼病活性得到了表征。这些化合物与PTD相比具有抗利什曼病活性，IC50值范围从0.6到7.27μM，SI值满意。正在进行涉及其他利什曼病菌株的进一步药理学评估，这将有助于选择最佳的命中物进行体内实验。
• Bicyclic pyrimidine derivatives with a bridgehead nitrogen atom. Part I. Synthesis of s-triazolo[4,3-a]pyrimidines
  作者：R. G. W. Spickett、S. H. B. Wright

  DOI：10.1039/j39670000498

  日期：——

  imidate hydrochlorides has been explored as a new route to 3-substituted s-triazolo[4,3-a]pyrimidines. The synthesis of certain s-triazolo[4,3-a]pyrimid-7-ones by lead tetra-acetate oxidation of 1-alkyl-2-benzylidenehydrazinopyrimid-6-ones is described. 6-Ethoxycarbonyl-s-triazolo[4,3-a]pyrimid-7-ones readily isomerise to s-triazolo[1,5-a]pyrimid-5-ones.

  已经探索了2-肼基嘧啶与亚氨酸乙酯盐酸盐的反应，作为制备3-取代的s-三唑并[4，3- a ]嘧啶的新途径。描述了通过1-烷基-2-亚苄基肼基嘧啶-6-酮的四乙酸铅氧化来合成某些s-三唑并[4，3 - a ]嘧啶-7-的方法。6-乙氧基羰基小号-三唑并[4,3-一个]嘧啶-7-酮容易异构化，以小号-三唑并[1,5-一个]嘧啶-5-酮。
• Biologically Active Guanidines and Related Compounds. II. Some Antiinflammatory Aminoguanidines¹
  作者：G. J. Durant、G. M. Smith、R. G. W. Spickett、S. H. B. Wright

  DOI：10.1021/jm00319a005

  日期：1966.1
• Lalezari,I. et al., Journal of Heterocyclic Chemistry, 1971, vol. 8, p. 689 - 691
  作者：Lalezari,I. et al.

  DOI：——

  日期：——
• Heinisch,L., Chemische Berichte, 1967, vol. 100, # 3, p. 893 - 904
  作者：Heinisch,L.

  DOI：——

  日期：——