N³-(pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine | 106580-75-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N³-(pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine
• 英文别名: 1H-1,2,4-Triazole-3,5-diamine, N5-3-pyridinyl-；3-N-pyridin-3-yl-1H-1,2,4-triazole-3,5-diamine
• CAS: 106580-75-0
• 化学式: C₇H₈N₆
• 分子量: 176.181
• InChiKey: IFUMPCXLMHBJQK-UHFFFAOYSA-N

物化性质

• 沸点：
  472.6±37.0 °C(Predicted)
• 密度：
  1.522±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  92.5
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N³-(pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine 、 异氰酸苯酯 在 silica 、 乙酸乙酯 、 Hexanes 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.02h， 以to afford compound the title compound (22.0 mg, 17%)的产率得到5-amino-3-(3-pyridylamino)-[1,2,4]triazole-1-carboxylic acid phenylamide
  参考文献：
  名称：

  DIAMINOTRIAZOLES USEFUL AS INHIBITORS OF PROTEIN KINASES

  摘要：

  本发明涉及蛋白激酶抑制剂。该发明还提供了包含本发明化合物的药物组合物以及使用该组合物治疗各种疾病的方法。

  公开号：

  US20080014189A1
• 作为产物：
  描述：

  3-cyano-1-(3-pyridinyl)-2-phenylisourea 在 肼 作用下， 以 四氢呋喃 为溶剂， 生成 N³-(pyridin-3-yl)-1H-1,2,4-triazole-3,5-diamine
  参考文献：
  名称：

  Diamino-1,2,4-triazole derivatives are selective inhibitors of TYK2 and JAK1 over JAK2 and JAK3

  摘要：

  Tyrosine kinase 2 (TYK2) is required for signaling of interleukin-23 (IL-23), which plays a key role in rheumatoid arthritis. Presented is the design and synthesis of 1,2,4-triazoles, and the evaluation of their inhibitory activity against the Janus associated kinases TYK2 and JAKs 1-3. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.026

文献信息

• Acylated 1<i>H</i>-1,2,4-Triazol-5-amines Targeting Human Coagulation Factor XIIa and Thrombin: Conventional and Microscale Synthesis, Anticoagulant Properties, and Mechanism of Action
  作者：Marvin Korff、Lukas Imberg、Jonas M. Will、Nico Bückreiß、Svetlana A. Kalinina、Benjamin M. Wenzel、Gregor A. Kastner、Constantin G. Daniliuc、Maximilian Barth、Ruzanna A. Ovsepyan、Kirill R. Butov、Hans-Ulrich Humpf、Matthias Lehr、Mikhail A. Panteleev、Antti Poso、Uwe Karst、Torsten Steinmetzer、Gerd Bendas、Dmitrii V. Kalinin

  DOI：10.1021/acs.jmedchem.0c01635

  日期：2020.11.12

  We herein report the conventional and microscale parallel synthesis of selective inhibitors of human blood coagulation factor XIIa and thrombin exhibiting a 1,2,4-triazol-5-amine scaffold. Structural variations of this scaffold allowed identifying derivative 21i, a potent 29 nM inhibitor of FXIIa, with improved selectivity over other tested serine proteases and also finding compound 21m with 27 nM

  我们在此报告了常规和微观并行合成的人类凝血因子XIIa和凝血酶的选择性抑制剂，这些抑制剂表现出1,2,4-三唑-5-胺骨架。该支架的结构变异允许鉴定衍生物21i（一种有效的FXIIa抑制剂29nM），具有比其他经过测试的丝氨酸蛋白酶更高的选择性，还可以发现化合物21m对凝血酶具有27 nM的抑制活性。首次证明酰化的1,2,4-三唑-5-胺具有抗凝特性，并具有影响凝血酶和癌细胞诱导的血小板凝集的能力。进行的质谱分析和分子建模使我们能够发现合成的抑制剂与FXIIa活性位点之间以前未知的相互作用，从而揭示了FXIIa抑制的机理细节。合成的化合物代表了开发新的抗血栓药物或化学工具以研究FXIIa和凝血酶在生理和病理过程中的作用的有希望的起点。
• Diaminotriazoles useful as inhibitors of protein kinases
  申请人：——

  公开号：US20040214817A1

  公开（公告）日：2004-10-28

  The present invention relates to inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

  本发明涉及蛋白激酶抑制剂。本发明还提供了包含本发明化合物的制药组合物以及使用该组合物治疗各种疾病的方法。
• 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
• [EN] DIAMINOTRIAZOLES USEFUL AS INHIBITORS OF PROTEIN KINASES<br/>[FR] DIAMINOTRIAZOLES CONVENANT COMME INHIBITEURS DE PROTEINE KINASES
  申请人：VERTEX PHARMA

  公开号：WO2004046120A3

  公开（公告）日：2004-08-12
• Highly Potent Inhibitors of Methionine Aminopeptidase-2 Based on a 1,2,4-Triazole Pharmacophore
  作者：Joseph P. Marino,、Paul W. Fisher、Glenn A. Hofmann、Robert B. Kirkpatrick、Cheryl A. Janson、Randall K. Johnson、Chun Ma、Michael Mattern、Thomas D. Meek、M. Dominic Ryan、Christina Schulz、Ward W. Smith、David G. Tew、Thaddeus A. Tomazek、Daniel F. Veber、Wenfang C. Xiong、Yuuichi Yamamoto、Keizo Yamashita、Guang Yang、Scott K. Thompson

  DOI：10.1021/jm061182w

  日期：2007.8.1

  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.