N²,N⁴-dimethyl-2,4-diamino-6-hydrazinyl-[1,3,5]triazine | 10409-79-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: N²,N⁴-dimethyl-2,4-diamino-6-hydrazinyl-[1,3,5]triazine
• 英文别名: 2-Hydrazino-4.6-bis-(monomethylamino)-1.3.5-triazin；6-hydrazino-N,N'-dimethyl-[1,3,5]triazine-2,4-diamine；6-Hydrazinyl-n,n'-dimethyl-1,3,5-triazine-2,4-diamine；6-hydrazinyl-2-N,4-N-dimethyl-1,3,5-triazine-2,4-diamine
• CAS: 10409-79-7
• 化学式: C₅H₁₁N₇
• mdl: MFCD19201351
• 分子量: 169.189
• InChiKey: FCGOPCWLSUHJHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  101
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-硝基糠醛 、 N²,N⁴-dimethyl-2,4-diamino-6-hydrazinyl-[1,3,5]triazine 以 甲醇 为溶剂， 以71%的产率得到4-N,6-N-dimethyl-2-N-[(E)-(5-nitrofuran-2-yl)methylideneamino]-1,3,5-triazine-2,4,6-triamine
  参考文献：
  名称：

  Design and Synthesis of a Series of Melamine-based Nitroheterocycles with Activity against Trypanosomatid Parasites

  摘要：

  The parasites that give rise to human African trypanosomiasis (HAT) are auxotrophs for various nutrients from the human host, including purines. They have specialist nucleoside transporters to import these metabolites. In addition to uptake of purine nucleobases and purine nucleosides, one of these transporters, the P2 transporter, can carry melamine derivatives; these derivatives are not substrates for the corresponding mammalian transporters. In this paper, we report the coupling of the melamine moiety to selected nitro heterocycles with the aim of selectively delivering these compounds to the parasites. Some compounds prepared have similar in vitro trypanocidal activities as melarsoprol, the principal drug used against late-stage HAT, with 50% growth inhibitory concentrations in the submicromolar range. Selected compounds were also evaluated in vivo in rodent models infected with Trypanosoma brucei brucei and T brucei rhodesiense and showed pronounced activity and in two cases were curative without overt signs of toxicity. Compounds were also tested against other trypanosomatid pathogens, Leishmania donovani and Trypanosoma cruzi, and significant activity in vitro was noted for T cruzi against which various nitro heterocycles are already registered for use.

  DOI：

  10.1021/jm050177+
• 作为产物：
  描述：

  2,4-Bismethylamino-6-chlor-1,3,5-triazin 在 一水合肼 作用下， 生成 N²,N⁴-dimethyl-2,4-diamino-6-hydrazinyl-[1,3,5]triazine
  参考文献：
  名称：

  Trypanocidal Activity of Melamine-Based Nitroheterocycles

  摘要：

  摘要 研究人员设计了一系列与三聚氰胺或联苯胺基团连接的硝基杂环化合物，这些基团是非洲布氏锥虫中 P2 氨基嘌呤和其他转运体的已知底物。一些化合物显示出体外锥虫毒性，50% 的抑制浓度在亚微摩范围内。虽然大多数化合物都能与 P2 转运体相互作用，因为它们能抑制腺苷通过这一载体的转运，但通过这一途径摄取腺苷并不是活性的必要条件，因为 TbAT1 和 TbAT2 转运体都能抑制腺苷的转运。 TbAT1 -缺失这种转运体的突变寄生虫对这些药物仍然敏感。一种与三聚氰胺相连的硝基呋喃化合物对小鼠体内的寄生虫也显示出明显的活性。对这种化合物作用模式的研究表明，还原压力和氧化压力都与这种化合物的杀锥虫活性无关，这就排除了它对布鲁氏原虫的基因毒性作用。 布氏锥虫 因此，它有别于其他一些对哺乳动物细胞有毒的杀锥虫硝基杂环化合物。

  DOI：

  10.1128/aac.48.5.1733-1738.2004

文献信息

• Trypanocidal Activity of Melamine-Based Nitroheterocycles
  作者：Mhairi L. Stewart、Gorka Jimenez Bueno、Alessandro Baliani、Burkhard Klenke、Reto Brun、Janice M. Brock、Ian H. Gilbert、Michael P. Barrett

  DOI：10.1128/aac.48.5.1733-1738.2004

  日期：2004.5

  A series of nitroheterocyclic compounds were designed with linkages to melamine or benzamidine groups that are known substrates of the P2 aminopurine and other transporters in African trypanosomes of the brucei group. Several compounds showed in vitro trypanotoxicity with 50% inhibitory concentrations in the submicromolar range. Although most compounds interacted with the P2 transporter, as judged by their ability to inhibit adenosine transport via this carrier, uptake through this route was not necessary for activity since TbAT1 -null mutant parasites, deficient in this transporter, retained sensitivity to these drugs. One compound, a melamine-linked nitrofuran, also showed pronounced activity against parasites in mice. Studies into the mode of action of this compound indicated that neither reductive, nor oxidative, stress were related to its trypanocidal activity ruling out a genotoxic effect in T. brucei , distinguishing it from some other, mammalian cell toxic, trypanocidal nitroheterocycles.

  摘要 研究人员设计了一系列与三聚氰胺或联苯胺基团连接的硝基杂环化合物，这些基团是非洲布氏锥虫中 P2 氨基嘌呤和其他转运体的已知底物。一些化合物显示出体外锥虫毒性，50% 的抑制浓度在亚微摩范围内。虽然大多数化合物都能与 P2 转运体相互作用，因为它们能抑制腺苷通过这一载体的转运，但通过这一途径摄取腺苷并不是活性的必要条件，因为 TbAT1 和 TbAT2 转运体都能抑制腺苷的转运。 TbAT1 -缺失这种转运体的突变寄生虫对这些药物仍然敏感。一种与三聚氰胺相连的硝基呋喃化合物对小鼠体内的寄生虫也显示出明显的活性。对这种化合物作用模式的研究表明，还原压力和氧化压力都与这种化合物的杀锥虫活性无关，这就排除了它对布鲁氏原虫的基因毒性作用。 布氏锥虫 因此，它有别于其他一些对哺乳动物细胞有毒的杀锥虫硝基杂环化合物。
• Fullerene derivatized s-triazine analogues as antimicrobial agents
  作者：Anish Kumar、Shobhana Karuveettil Menon

  DOI：10.1016/j.ejmech.2008.10.036

  日期：2009.5

  A series of novel fullerene derivatives bearing s-triazine moiety have been synthesized by adopting 1,3 dipolar cycloaddition reaction of C60 and azomethine ylides generated from the corresponding Schiff bases of 2,4,6 trisubstituted s-triazine. All the compounds synthesized were characterized by elemental analysis, FT-IR, 1H NMR, 13C NMR and FAB-MS. The compounds were then screened for their antibacterial

  通过采用C 60的1，3偶极环加成反应和由2，4，6三取代的s－三嗪的相应席夫碱生成的偶氮甲碱，合成了一系列带有s－三嗪部分的富勒烯衍生物。通过元素分析，FT-IR，1 H NMR，13 C NMR和FAB-MS对合成的所有化合物进行表征。然后筛选化合物对革兰氏阳性（金黄色葡萄球菌，枯草芽孢杆菌，枯草芽孢杆菌）和革兰氏阴性（大肠杆菌，铜绿假单胞菌和通过圆盘扩散法分离出肺炎克雷伯菌。发现所有化合物均以非常低的浓度对这些菌株具有活性，并且与标准药物环丙沙星相当。
• AYYANGAR N. R.; LAHOTI R. J.; WAGLE D. R., INDIAN J. CHEM., 1979, B18, NO 2, 196-197
  作者：AYYANGAR N. R.、 LAHOTI R. J.、 WAGLE D. R.

  DOI：——

  日期：——
• Cardioprotective effect of novel sulphonamides-1,3,5-triazine conjugates against ischaemic-reperfusion injury via selective inhibition of MMP-9
  作者：Xiao-Zhu Zheng、Jia-Li Zhou、Jing Ye、Pei-Pei Guo、Chun-Shui Lin

  DOI：10.1111/cbdd.12807

  日期：2016.11

  Diseases affecting cardiovascular system are ranked as a top most cause of morbidity and mortality. Herein, a novel class sulphonamides‐1,3,5‐triazine conjugates have been synthesized and tested for inhibitory activity against MMP‐2 and MMP‐9. The results of the study showed that these molecules efficiently inhibit MMP‐9 than MMP‐2, revealing compound 8e as the most potent inhibitor (IC50 = 2.34 ± 0.56 nm). Due to involvement of MMP‐9 in many cardiovascular diseases, particularly in myocardial ischaemia (MI), compound 8e was further subjected for the determination of the protective effect on isoproterenol (ISO)‐induced myocardial injury in rats.
• Design and Synthesis of a Series of Melamine-based Nitroheterocycles with Activity against Trypanosomatid Parasites
  作者：Alessandro Baliani、Gorka Jimenez Bueno、Mhairi L. Stewart、Vanessa Yardley、Reto Brun、Michael P. Barrett、Ian H. Gilbert

  DOI：10.1021/jm050177+

  日期：2005.8.1

  The parasites that give rise to human African trypanosomiasis (HAT) are auxotrophs for various nutrients from the human host, including purines. They have specialist nucleoside transporters to import these metabolites. In addition to uptake of purine nucleobases and purine nucleosides, one of these transporters, the P2 transporter, can carry melamine derivatives; these derivatives are not substrates for the corresponding mammalian transporters. In this paper, we report the coupling of the melamine moiety to selected nitro heterocycles with the aim of selectively delivering these compounds to the parasites. Some compounds prepared have similar in vitro trypanocidal activities as melarsoprol, the principal drug used against late-stage HAT, with 50% growth inhibitory concentrations in the submicromolar range. Selected compounds were also evaluated in vivo in rodent models infected with Trypanosoma brucei brucei and T brucei rhodesiense and showed pronounced activity and in two cases were curative without overt signs of toxicity. Compounds were also tested against other trypanosomatid pathogens, Leishmania donovani and Trypanosoma cruzi, and significant activity in vitro was noted for T cruzi against which various nitro heterocycles are already registered for use.