3-Amino-5-p-toluidino-1.2.4-triazol | 3929-18-8

• 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: 3-Amino-5-p-toluidino-1.2.4-triazol
• 英文别名: 3-N-(4-methylphenyl)-1H-1,2,4-triazole-3,5-diamine
• CAS: 3929-18-8
• 化学式: C₉H₁₁N₅
• mdl: MFCD25963077
• 分子量: 189.22
• InChiKey: NBIHCSWIGABDMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  79.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-Amino-5-p-toluidino-1.2.4-triazol 在 五氯化磷 、 溶剂黄146 作用下， 反应 24.0h， 生成 C₁₃H₁₂ClN₅
  参考文献：
  名称：

  强效抗微管药物高活性 7-苯胺基三唑并嘧啶的合成及生物学评价

  摘要：

  两个不同系列的 52 种化合物，基于 3',4',5'-三甲氧基苯胺 ( 7a–ad ) 和在 2-取代的-[1,2 的 7 位上可变取代的苯胺 ( 8a–v ) ,4]三唑并[1,5- a ]嘧啶核，对 A549、MDA-MB-231、HeLa、HT-29 和 Jurkat 癌细胞系具有中度至强效的抗增殖活性。所有衍生物在三唑并嘧啶支架的2位上具有共同的3-苯基丙氨基部分，并且在其7位上具有不同的卤素取代的苯胺，对应于4'-氟苯胺( 8q )、4'-氟-3'-氯苯胺( 8r )、4'-氯苯胺 ( 8s ) 和 4'-溴苯胺 ( 8u ) 显示出最大的抗增殖活性，平均 IC 50' s 分别为 83、101、91 和 83 nM。这四种化合物对微管蛋白聚合的抑制作用比考布他汀 A-4 (CA-4) 强约 2 倍，并且它们作为 [ 3 H]秋水仙碱与微管蛋白结合的抑制剂的活性与 CA-4 相似。这些数据强调，[1

  DOI：

  10.3390/pharmaceutics14061191
• 作为产物：
  描述：

  2,4-Dithio-1-(p-tolyl)biuret 在 溶剂黄146 、 三乙胺 、 肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.17h， 生成 3-Amino-5-p-toluidino-1.2.4-triazol
  参考文献：
  名称：

  Highly Potent Inhibitors of Methionine Aminopeptidase-2 Based on a 1,2,4-Triazole Pharmacophore

  摘要：

  High-throughput screening for inhibitors of the human metalloprotease, methionine aminopeptidase-2 (MetAP2), identified a potent class of 3-anilino-5-benzylthio-1,2,4-triazole compounds. Efficient array and interative synthesis of triazoles led to rapid SAR development around the aniline, benzylthio, and triazole moeities. Evaluation of these analogs in a human MetAP2 enzyme assay led to the identification of several inhibitors with potencies in the 50-100 picomolar range. The deleterious effects on inhibitor potency by methylation of the anilino-triazole nitrogens, as well as the X-ray crystal structure of triazole 102 bound in the active site of MetAP2, confirm the key interactions between the triazole nitrogens, the active site cobalt atoms, and the His-231 side-chain. The structure has also provided a rationale for interpreting SAR within the triazole series. Key aniline (2-isopropylphenyl) and sulfur substituents (furanylmethyl) identified in the SAR studies led to the identification of potent inhibitors (103 and 104) of endothelial cell proliferation. Triazoles 103 and 104 also exhibited dose-dependent activity in an aortic ring tissue model of angiogenesis highlighting the potential utility of MetAP2 inhibitors as anticancer agents.

  DOI：

  10.1021/jm061182w

文献信息

• A one-pot, three-component, microwave-promoted synthesis of 2-amino-substituted 7-amino-1,2,4-triazolo[1,5-a][1,3,5]triazines
  作者：Svetlana A. Kalinina、Dmitrii V. Kalinin、Anton V. Dolzhenko

  DOI：10.1016/j.tetlet.2013.07.158

  日期：2013.10

  A new, efficient, catalyst-free, one-pot, three-component method for the synthesis of 2-amino-substituted 7-amino-1,2,4-triazolo[1,5-a][1,3,5]triazines using 3,5-diamino-1,2,4-triazoles, cyanamide, and triethyl orthoformate is developed. The reaction proceeds smoothly under microwave-assisted heating. Advantages of the method include using easily available reagents, short reaction times, and operational

  一种新型，高效，无催化剂的单锅三组分方法，用于合成2-氨基取代的7-氨基-1,2,4-三唑[1,5- a ] [1,3,5开发了使用3,5-二氨基-1,2,4-三唑，氰胺和原甲酸三乙酯的三嗪。反应在微波辅助加热下顺利进行。该方法的优点包括使用容易获得的试剂，较短的反应时间和操作简便。
• Inhibition of Copper Corrosion with N-Arylaminotriazoles in Aqueous Chloride Solutions and in Air
  作者：D. S. Shevtsov、Kh. S. Shikhaliev、E. S. Komarova、A. A. Kruzhilin、G. O. Kipriyanova、A. Yu. Potapov、I. D. Zartsyn、O. A. Kozaderov、Ch. Prabhakar、A. Tripathi

  DOI：10.1134/s1070427220080078

  日期：2020.8

  3-(N-arylamino)-5-amino-1Н-1,2,4-triazoles were prepared by the reaction of S,S-dimethyl cyanodithioimidocarbamate with appropriate anilines. The inhibiting effect of the products on the corrosion of copper of M1 grade in acidic and neutral chloride-containing media was studied using electrochemical and accelerated electroless methods. The maximal degree of protection ensured by commercially available

  摘要 一系列3-（Ñ -arylamino）1-5氨基Н -1,2,4-三唑经反应制得S，S与适当的苯胺-二甲基cyanodithioimidocarbamate。用电化学和加速化学方法研究了产物对酸性和中性氯化物介质中M1级铜腐蚀的抑制作用。通过商业上可获得的3,5-二氨基-1 H -1,2,4-三唑和合成的3-苯基氨基，3-（4-甲基苯基氨基），3-（4-氯苯基氨基）和3可以确保最大程度的保护。5-氨基-1Н-的-（3-氯苯基氨基）衍生物1,2,4-三唑达到70-87％。在酸性溶液中，合成的化合物显示出比3,5-二氨基衍生物更高的性​​能，可确保高达92–96％的保护率。在盐雾室中的实验中获得了相似的结果。
• A comparative study of fragment screening methods on the p38α kinase: new methods, new insights
  作者：Scott J. Pollack、Kim S. Beyer、Christopher Lock、Ilka Müller、David Sheppard、Mike Lipkin、David Hardick、Peter Blurton、Philip M. Leonard、Paul A. Hubbard、Daniel Todd、Christine M. Richardson、Thomas Ahrens、Manuel Baader、Doris O. Hafenbradl、Kate Hilyard、Roland W. Bürli

  DOI：10.1007/s10822-011-9454-9

  日期：2011.7

  The stress-activated kinase p38α was used to evaluate a fragment-based drug discovery approach using the BioFocus fragment library. Compounds were screened by surface plasmon resonance (SPR) on a Biacore™ T100 against p38α and two selectivity targets. A sub-set of our library was the focus of detailed follow-up analyses that included hit confirmation, affinity determination on 24 confirmed, selective hits and competition assays of these hits with respect to a known ATP binding site inhibitor. In addition, functional activity against p38α was assessed in a biochemical assay using a mobility shift platform (LC3000, Caliper LifeSciences). A selection of fragments was also evaluated using fluorescence lifetime (FLEXYTE™) and microscale thermophoresis (Nanotemper) technologies. A good correlation between the data for the different assays was found. Crystal structures were solved for four of the small molecules complexed to p38α. Interestingly, as determined both by X-ray analysis and SPR competition experiments, three of the complexes involved the fragment at the ATP binding site, while the fourth compound bound in a distal site that may offer potential as a novel drug target site. A first round of optimization around the remotely bound fragment has led to the identification of a series of triazole-containing compounds. This approach could form the basis for developing novel and active p38α inhibitors. More broadly, it illustrates the power of combining a range of biophysical and biochemical techniques to the discovery of fragments that facilitate the development of novel modulators of kinase and other drug targets.

  利用 BioFocus 片段库评估了一种基于片段的药物发现方法，即应激活化激酶 p38α。在 Biacore™ T100 上通过表面等离子体共振 (SPR) 针对 p38α 和两个选择性目标筛选化合物。我们对文库中的一个子集进行了详细的后续分析，包括对 24 个已确认的选择性命中物进行命中确认、亲和力测定，以及这些命中物与已知 ATP 结合位点抑制剂的竞争分析。此外，还使用迁移率平台（LC3000，Caliper LifeSciences）在生化试验中评估了针对 p38α 的功能活性。还利用荧光寿命（FLEXYTE™）和微尺度热电泳（Nanotemper）技术对部分片段进行了评估。不同检测方法的数据之间具有良好的相关性。解决了四种小分子与 p38α 复合物的晶体结构问题。有趣的是，通过 X 射线分析和 SPR 竞争实验确定，其中三个复合物涉及 ATP 结合位点上的片段，而第四个化合物则结合在一个远端位点上，该位点有可能成为新型药物的靶点。围绕远程结合位点片段进行的第一轮优化，确定了一系列含三唑的化合物。这种方法可作为开发新型活性 p38α 抑制剂的基础。更广泛地说，它说明了结合一系列生物物理和生物化学技术发现片段的威力，这些片段有助于开发激酶和其他药物靶点的新型调节剂。
• TRIAZOLE DERIVATIVES USEFUL AS AXL INHIBITORS
  申请人：Singh Rajinder

  公开号：US20110082131A1

  公开（公告）日：2011-04-07

  Methods of using triazole derivatives in treating diseases or conditions associated with Axl catalytic activity are disclosed.

  本发明揭示了使用三唑衍生物治疗与Axl催化活性相关的疾病或病症的方法。
• Design, Synthesis and Biological Investigation of 2-Anilino Triazolopyrimidines as Tubulin Polymerization Inhibitors with Anticancer Activities
  作者：Romeo Romagnoli、Paola Oliva、Filippo Prencipe、Stefano Manfredini、Federica Budassi、Andrea Brancale、Salvatore Ferla、Ernest Hamel、Diana Corallo、Sanja Aveic、Lorenzo Manfreda、Elena Mariotto、Roberta Bortolozzi、Giampietro Viola

  DOI：10.3390/ph15081031

  日期：——

  investigation aiming to generate new potential antitumor agents led us to synthesize a new series of twenty-two compounds characterized by the presence of the 7-(3′,4′,5′-trimethoxyphenyl)-[1,2,4]triazolo[1,5-a]pyrimidine pharmacophore modified at its 2-position. Among the synthesized compounds, three were significantly more active than the others. These bore the substituents p-toluidino (3d), p-ethylanilino

  旨在产生新的潜在抗肿瘤药物的进一步研究使我们合成了一系列新的 22 种化合物，其特征是存在 7-(3',4',5'-三甲氧基苯基)-[ 1 , 2 ,4]三唑并[1,5- a ]嘧啶药效团在其2-位进行修饰。在合成的化合物中，三种化合物的活性明显高于其他化合物。这些带有取代基对甲苯胺基 ( 3d )、对乙基苯胺基 ( 3h ) 和 3',4'-二甲基苯胺基 ( 3f )，这些化合物的 IC 50值为 30–43、160–240 和 67–160 nM，分别针对 HeLa、A549 和 HT-29 癌细胞。对甲苯胺衍生物3d是最有效的微管蛋白聚合抑制剂 (IC 50 : 0.45 µM)，并强烈抑制秋水仙碱与微管蛋白的结合（抑制 72%），对 A549 和 HeLa 癌细胞的抗增殖活性优于 CA-4线。体外研究表明，化合物3d能够将处理的细胞阻断在细胞周期的 G2/M 期，并按照内在途径诱导细胞凋亡，线粒体去极化和