5-(4-甲基苯基)-4H-1,2,4-三唑-3-胺 | 51884-11-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 5-(4-甲基苯基)-4H-1,2,4-三唑-3-胺
• 英文名称: 5-p-tolyl-2H-1,2,4-triazol-3-amine
• 英文别名: 3-(p-tolyl)-5-amino-1,2,4-triazole；3-(p-tolyl)-1H-1,2,4-triazol-5-amine；5-(4-methylphenyl)-1H-1,2,4-triazol-3-amine
• CAS: 51884-11-8
• 化学式: C₉H₁₀N₄
• mdl: MFCD00465596
• 分子量: 174.205
• InChiKey: OFNBXLBLUCECGY-UHFFFAOYSA-N

物化性质

• 密度：
  1.261

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  67.6
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 5-(4-Methylphenyl)-4h-1,2,4-triazol-3-amine
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: 5-(4-Methylphenyl)-4h-1,2,4-triazol-3-amine
CAS number: 51884-11-8

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C9H10N4
Molecular weight: 174.2

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  5-(4-甲基苯基)-4H-1,2,4-三唑-3-胺 在 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.33h， 生成 2-(4-methylphenyl)-5-thioxo-5,6-dihydro-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(4H)-one
  参考文献：
  名称：

  A structure–activity relationship study of 1,2,4-triazolo[1,5-a][1,3,5]triazin-5,7-dione and its 5-thioxo analogues on anti-thymidine phosphorylase and associated anti-angiogenic activities

  摘要：

  Thirty-three 1,2,4-triazolo[1,5-a][1,3,5]triazin-5,7-dione and its 5-thioxo analogues were designed and synthesized which contained different substituents at meta- and/or para-positions of 2-phenyl or 2-benzyl ring attached to the fused ring structure. The preliminary pharmacological evaluation demonstrated that the 5-thioxo analogues of 1,2,4-triazolo[1,5-a][1,3,5]triazine exhibited a varying degree of inhibitory activity towards thymidine phosphorylase, comparable or better than reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value = 42.63 mu M). Moreover, compounds 5q and 6i displayed a mixed-type of inhibitory mechanism in the presence of variable concentrations of thymidine (dThd). In addition, selected compounds were found to have a noticeable inhibitory effect on the expression of angiogenesis markers, including VEGF and MMP-9 in MDA-MB-231 breast cancer cells. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.06.051
• 作为产物：
  描述：

  N-Amidino-(p-methyl)benzohydrazid 在 sodium hydroxide 作用下， 反应 36.0h， 以58%的产率得到5-(4-甲基苯基)-4H-1,2,4-三唑-3-胺
  参考文献：
  名称：

  高效微管蛋白聚合抑制剂的发现：新型 2,7-二芳基-[1,2,4] 三唑并 [1,5-a] 嘧啶的设计、合成和构效关系

  摘要：

  通过去除我们之前报道的化合物3 中的5-甲基和 6-乙酰基，我们设计了一系列新型 2,7-二芳基-[1,2,4] 三唑并 [1,5- a ] 嘧啶衍生物作为潜在的微管蛋白聚合抑制剂。其中，化合物5e对 HeLa 细胞显示出低纳摩尔的抗增殖功效，比铅类似物3高 166 倍。有趣的是，与 HEK-293（正常人胚胎肾细胞）相比，5e在抑制癌细胞方面表现出显着的选择性。此外，5e通过改变 p-cdc2 和细胞周期蛋白 B1 的表达水平，剂量依赖性地将 HeLa 阻滞在 G2/M 期，并通过调节裂解的 PARP 的表达导致 HeLa 细胞凋亡。进一步的证据表明，5e有效地抑制了微管蛋白聚合，并且比阳性对照 CA-4 强 3 倍。此外，分子对接分析表明，5e与秋水仙碱结合位点中的 CA-4 重叠良好。这些研究表明，2,7-二芳基-[1,2,4]三唑并[1,5- a ]嘧啶骨架可用作开发新型微管蛋白聚合抑制剂作为潜在抗癌剂的主要单元。

  DOI：

  10.1016/j.ejmech.2021.113449

文献信息

• Discovery of [1,2,4]-triazolo [1,5-a]pyrimidine-7(4H)-one derivatives as positive modulators of GABAA1 receptor with potent anticonvulsant activity and low toxicity
  作者：Longjiang Huang、Jing Ding、Min Li、Zhipeng Hou、Yanru Geng、Xiufen Li、Haibo Yu

  DOI：10.1016/j.ejmech.2019.111824

  日期：2020.1

  antiepileptic drugs, a series of 2,5-disubstituted [1,2,4]-triazolo[1,5-a]pyrimidine-7(4H)-one derivatives were designed and synthesized. Spontaneous Ca2+ oscillations (SCOs) of cortical neurons were used for in vitro phenotypic screening. Maximal electroshock test (MES) and pentylenetetrazole (PTZ) test were used to access their anticonvulsant activity, and rotarod test was used to estimate their neurotoxicity

  为了寻找更有效，更安全的抗癫痫药，设计并合成了一系列2,5-二取代的[1,2,4]-三唑并[1,5-a]嘧啶-7（4H）-one衍生物。皮层神经元的自发Ca 2+振荡（SCO）用于体外表型筛选。使用最大电击试验（MES）和戊四唑（PTZ）试验来获得其抗惊厥活性，并使用rotarod试验评估其神经毒性。体外模型中的活性化合物在戊四氮（PTZ）诱发的癫痫模型中特别有效，但在最大电击（MES）模型中无效，与常用药物相比，更重要的是具有较低的神经毒性。其中，化合物5c和5e在PTZ诱发的癫痫模型中显示出显着的抗惊厥活性，ED50值分别为31.81 mg / kg和40.95 mg / kg，分别。这些化合物具有改善的神经毒性，其保护指数（PI = TD50 / ED50）值分别为17.22和9.09。最后，我们证明了化合物5c和5e主要作为正调节剂作用于GABAA受体，但没有钠通道。因此，本研究为癫痫的进一步研究提供了潜在的候选者。
• Discovery of 7-alkyloxy- [1,2,4] triazolo[1,5-a] pyrimidine derivatives as selective positive modulators of GABAA1 and GABAA4 receptors with potent antiepileptic activity
  作者：Jun Wu、Zhipeng Hou、Yan Wang、Liping Chen、Chengxi Lian、Qingfei Meng、Chaoying Zhang、Xiufen Li、Longjiang Huang、Haibo Yu

  DOI：10.1016/j.bioorg.2021.105565

  日期：2022.2

  Further studies demonstrated that the anticonvulsant activity of these compounds mainly depended on their allosteric potentiation of GABAA receptors. Among them, compound 10c was picked for the mechanism study due to its potent activity. The compound is more sensitive to subunit configurations of synaptic α1β2γ2 and extrasynaptic α4β3δ GABAA receptors, but there were no effects on NMDA receptors and Nav1

  设计合成了一系列7-烷氧基-[1,2,4]三唑并[1,5-a]嘧啶衍生物。最大电击 (MES) 和戊四唑 (PTZ) 测试用于评估其抗惊厥活性。该系列化合物中的大多数都表现出显着的抗癫痫作用。进一步的研究表明，这些化合物的抗惊厥活性主要取决于它们对 GABA A受体的变构增强作用。其中，化合物10c因其强大的活性而被选中进行机理研究。该化合物对突触 α1β2γ2 和突触外 α4β3δ GABA A受体的亚基构型更敏感，但对 NMDA 受体和 Nav1.2 钠通道没有影响。同时，10c作用于不同于常用抗惊厥药苯二氮卓类和巴比妥类药物的 GABA A受体位点。此外，对天然神经元的研究表明，化合物10c还增强了天然 GABA A受体的活性，并降低了培养的皮层神经元的动作电位放电。这种结构化合物可能为进一步设计新型抗癫痫分子奠定基础。
• 3-Aryl/Heteroaryl-5-amino-1-(3′,4′,5′-trimethoxybenzoyl)-1,2,4-triazoles as antimicrotubule agents. Design, synthesis, antiproliferative activity and inhibition of tubulin polymerization
  作者：Romeo Romagnoli、Filippo Prencipe、Paola Oliva、Stefania Baraldi、Pier Giovanni Baraldi、Andrea Brancale、Salvatore Ferla、Ernest Hamel、Roberta Bortolozzi、Giampietro Viola

  DOI：10.1016/j.bioorg.2018.06.037

  日期：2018.10

  at the 3-position of the 5-amino-1,2,4-triazole system. Most of the twenty-two tested compounds showed moderate to potent antiproliferative activities against a panel of solid tumor and leukemic cell lines, with four (5j, 5k, 5o and 5p) showing strong antiproliferative activity (IC50 < 1 μM) against selected cancer cells. Among them, several molecules preferentially inhibited the proliferation of leukemic

  已知许多天然和合成物质会干扰微管蛋白的动态组装，从而阻止微管的形成。在我们寻找有效的和选择性的抗肿瘤剂中，合成了一系列新的1-（3'，4'，5'-三甲氧基苯甲酰基）-5-氨基-1,2,4-三唑。这些化合物具有不同的杂环，包括噻吩，呋喃或三个同分异构的吡啶，并且它们在5-氨基-1,2,4-三唑体系的3位上具有带电子释放或吸电子取代基的苯环。 。测试的22种化合物中的大多数对一组实体瘤和白血病细胞系均显示出中度至强效的抗增殖活性，其中4种（5j，5k，5o和5p） 对选定的癌细胞显示出强大的抗增殖活性（IC 50 <1μM）。其中，有几种分子优先抑制白血病细胞系的增殖，显示Jurkat和RS4; 11细胞的IC 50值比源自实体瘤的三系（HeLa，HT-29和MCF- 7个单元格）。化合物5k强烈抑制微管蛋白组装，IC 50值为0.66μM，是在CA-4的同时实验中获得的一半（IC 50  =
• A novel multicomponent microwave-assisted synthesis of 5-aza-adenines
  作者：Anton V. Dolzhenko、Svetlana A. Kalinina、Dmitrii V. Kalinin

  DOI：10.1039/c3ra41932k

  日期：——

  A novel multicomponent strategy for the efficient synthesis of 5-aza-adenines was developed. 5-Aza-adenines were prepared in a one-pot fashion from 5-amino-1,2,4-triazoles, cyanamide and triethyl orthoformate under microwave irradiation. The operational simplicity, efficiency and accessibility of this method make it highly attractive for the generation of bioactive compound libraries.

  开发了一种新型多组分策略，用于高效合成5-偶氮腺嘌呤。通过微波照射下，以5-氨基-1,2,4-三氮唑、氰脲酰胺和三乙基原甲酸酯在单一容器中制备了5-偶氮腺嘌呤。该方法操作简便、高效且易于实施，使其在生成生物活性化合物库方面极具吸引力。
• New factor Xa inhibitors based on 1,2,3,4-tetrahydroquinoline developed by molecular modelling
  作者：Ivan Ilin、Elena Lipets、Alexey Sulimov、Danil Kutov、Khidmet Shikhaliev、Andrey Potapov、Michael Krysin、Fedor Zubkov、Lyudmila Sapronova、Fazoyl Ataullakhanov、Vladimir Sulimov

  DOI：10.1016/j.jmgm.2019.03.017

  日期：2019.6

  Factor Xa is a serine protease representing a crucial element in the coagulation process and an attractive target for anticoagulant therapy. At the present time there are several chemical classes of factor Xa inhibitors with proven activity. Furthermore, three factor Xa inhibitors have been approved for the medical use to date. However, therapy with these medications is accompanied by substantial adverse

  Xa因子是一种丝氨酸蛋白酶，代表凝血过程中的关键要素，也是抗凝治疗的诱人靶标。目前，有几种化学类别的具有证实活性的Xa因子抑制剂。此外，迄今为止，已经批准了三种Xa因子抑制剂用于医疗用途。但是，使用这些药物进行治疗会带来严重的不良反应。在这种背景下，结合分子对接和半经验量子化学计算的基于结构的计算方法被用于寻找新的有效因子Xa抑制剂。我们进行了一些虚拟筛选程序，以选择潜在的候选对象进行合成和后续测试。聚焦文库的第一个筛选结果鉴定出20种化合物，其中7种化合物在溶解度允许的最大浓度下显示出对因子Xa的明显抑制作用。随后的其他屏幕确定了20个其他候选对象。其中，有5种物质在5μM时能抑制Xa因子。通过建模确定的发现的最好的两种1,2,3,4-四氢喹啉衍生物已证明其IC50值在微摩尔范围内。其中之一是对胰蛋白酶，因子IIa，IXa和XIa的选择性Xa抑制剂。通过建模鉴定的4-四氢喹啉衍生物已证明在微摩尔范围内的IC