3-氨基-1,2,4-三氮唑 | 65312-61-0

• 物质功能分类: 分析化学 - 标准品 - 化妆品标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-氨基-1,2,4-三氮唑
• 中文别名: 杀草强；去甲安乃近；氨三唑；磺甲比林；3-氨基-1,2,4-三唑；氨基三唑；甲磺比林钠；3-氨基-1H-1,2,4-三氮唑；阿米托；3-氨基-1,2,4-三氮杂茂；阿米坐
• 英文名称: 3(5)-amino-1,2,4-triazole
• 英文别名: 3-amino-1,2,4-triazole；3-amino-1H-1,2,4-triazole；1H-1,2,4-triazol-3-amine；aminotriazole；amitrole；1H-1,2,4-triazol-5-amine
• CAS: 65312-61-0；61-82-5；65312-62-1
• 化学式: C₂H₄N₄
• mdl: MFCD00005230
• 分子量: 84.0806
• InChiKey: KLSJWNVTNUYHDU-UHFFFAOYSA-N

物化性质

• 熔点：
  150-153 °C(lit.)
• 沸点：
  144.35°C (rough estimate)
• 密度：
  1.138
• 溶解度：
  280g/l
• 暴露限值：
  NIOSH REL: TWA 0.2 mg/m3; ACGIH TLV: TWA 0.2 mg/m3.
• LogP：
  -0.860
• 物理描述：
  Amitrole appears as odorless white crystals or white powder. Bitter taste. Melting point 147-159°C. Sublimes undecomposed at reduced pressure. Used as a post-emergence herbicide.
• 颜色/状态：
  Transparent to off white crystalline powder
• 气味：
  Odorless when pure.
• 味道：
  Bitter taste
• 蒸汽密度：
  Relative vapor density (air = 1): 2.9
• 蒸汽压力：
  4.4X10-7 mm Hg at 25 °C
• 稳定性/保质期：
  Stable in neutral, acidic and alkaline media; DT50 >30 days (pH 4-9, 23 °C). Photolysis DT50 >30 days (pH 5-9, 25 °C). Powerful chelating agent.
• 分解：
  When strongly heated it emits highly toxic fumes of /nitrogen oxides/.
• 腐蚀性：
  MILDLY CORROSIVE TO IRON, ALUMINUM, COPPER, & COPPER ALLOYS.
• 解离常数：
  pKa1 = 4.2; pKa2 = 10.7
• 保留指数：
  1300;1324

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  6
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  67.6
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

39岁女性服用20毫克/千克氨三唑后，几小时后收集的尿液中含有没有变化的氨三唑（100毫克/100毫升）。没有发现代谢物。

After 39-yr-old woman ingested 20 mg/kg of aminotriazole, urine taken some hours later contained unchanged aminotriazole (100 mg/100 mL). No metabolites were found.

来源:Hazardous Substances Data Bank (HSDB)

代谢

植物的代谢……植物中的甘氨酸和丝氨酸被用于生物合成β-(3-氨基-S-三唑基-1)-α-丙氨酸。

Metabolism... in plants: Glycine and serin of plants are utilized in biosynthesis of beta-(3-amino-S-triazolyl-1-)alpha-alanine.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在...关于加拿大蓟的研究中，观察到了3种化合物...其中一种被鉴定为beta-(3-氨基-1,2,4-三唑基-1)-alpha-丙氨酸)。

In... studies with Canada thistle, 3 compounds ... observed. One was identified as beta-(3-amino-1,2,4-triazolyl-1)-alpha-alanine).

来源:Hazardous Substances Data Bank (HSDB)

代谢

由微生物活动从氨基三唑形成的主要代谢产物是二氧化碳。... 大肠杆菌将3-氨基-1,2,4-三唑转化为代谢物，3-氨基-1,2,4-三唑基丙氨酸。

Major metabolic product formed from amitrole by microbiological activity was carbon dioxide. ... E coli converted 3-ATA into metabolite, 3-amino-1,2,4,-triazolyl alanine.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

癌症分类：B2组可能的人类致癌物

Cancer Classification: Group B2 Probable Human Carcinogen

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

美国环保局健康与环境评估办公室的人类健康评估小组对氨基茚进行了致癌性评估。根据他们的分析，氨基茚的证据权重为B2组，这一评估是基于人类证据不足和动物证据充分的结论。作为B2组化学物质，氨基茚被认为是一种可能的人类致癌物。

The Human Health Assessment Group in EPA's Office of Health and Environmental Assessment has evaluated amitrole for carcinogenicity. According to their analysis, the weight-of-evidence for amitrole is group B2, which is based on inadequate evidence in humans and sufficient evidence in animals. As a group B2 chemical, amitrole is considered a probable human carcinogen.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：对于阿米特罗在人类中的致癌性，目前尚缺乏足够的证据。在实验动物中，阿米特罗的致癌性有足够的证据。总体评估：阿米特罗的致癌性对人类不可分类（第3组）。在进行评估时，工作组认为阿米特罗通过一种非基因毒性的机制在小鼠和大鼠中产生甲状腺肿瘤，这种机制涉及干扰甲状腺过氧化酶的功能，导致循环甲状腺激素浓度降低和甲状腺刺激激素分泌增加。因此，阿米特罗不会预期在暴露于不改变甲状腺激素内环境稳定性的浓度下，会在人类中产生甲状腺癌。工作组基于阿米特罗缺乏基因毒性的额外考虑是，小鼠的肝肿瘤和大鼠的良性肿瘤也是通过一种非基因毒性机制产生的。来自流行病学研究以及实验动物毒理学研究的证据提供了令人信服的证据，表明在响应甲状腺激素失衡时，啮齿动物比人类对甲状腺肿瘤的发展要敏感得多。

Evaluation: There is inadequate evidence in humans for the carcinogenicity of amitrole. There is sufficient evidence in experimental animals for the carcinogenicity of amitrole. Overall evaluation: Amitrole is not classifiable as to its carcinogenicity to humans (Group 3). In making its evaluation, the Working Group concluded that amitrole produces thyroid tumors in mice and rats by a non-genotoxic mechanism, which involves interference with the functioning of the thyroid peroxidase, resulting in a reduction in circulating thyroid hormone concn and incr secretion of thyroid stimulating hormone. Consequently, amitrole would not be expected to produce thyroid cancer in humans exposed to concn that do not alter thyroid hormone homeostasis. An additional consideration of the Working Group, based on lack of genotoxicity of amitrole, was that the liver tumors in mice and benign tumors in rats were also produced by a non-genotoxic mechanism. Evidence from epidemiological studies and from toxicological studies in experimental animals provide compelling evidence that rodents are substantially more sensitive than humans to the development of thyroid tumors in response to thyroid hormone imbalance.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

A3; 已确认的动物致癌物，对人类的相关性未知。

A3; Confirmed animal carcinogen with unknown relevance to humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

Amitrole: 有合理预期对人来说是致癌物。

Amitrole: reasonably anticipated to be a human carcinogen.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

氨三唑被涂抹在兔子的皮肤上。15分钟后，它已经渗透进入血液。脂肪是...无关紧要的储存地点。

Aminotriazole was applied to skin of rabbits. After 15 min it had penetrated into the blood. Fat was ... /an/ inconsequential site of storage.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

威斯达大鼠通过胃管喂食了1毫克14C-氨基三唑（每只大鼠）。在给药后的三天内，对呼出的空气、尿液、粪便和组织进行了放射性分析。在最初的24小时内，70至95.5%的放射性物质在尿液中找到；粪便中发现了少量可变的活动。吸收后，氨基三唑分布到大多数身体组织中。肝和肾中发现了最大的放射性。在给药后三到四小时内，组织水平开始下降。纸层析法揭示了在大鼠给药后不同时间取的肝切片中既有未改变的氨基三唑也有一种未识别的代谢物。

Wistar rats were fed 1 mg 14C-amitrole (per rat) via stomach tube. The expired air, urine, feces and tissues were analyzed for radioactivity during a three day period following dosing. During the first 24 hours, 70 to 95.5% of the radioactivity was found in the urine; a small variable amount of activity was found in the feces. After absorption, amitrole was distributed throughout most body tissues. The maximum radioactivity was found in liver and kidney. Within three to four hours of dosing, the tissue levels began decreasing. Paper chromatography revealed both unchanged amitrole and one unidentified metabolite in rat liver slices taken at various times following dosing.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

主要接触途径是皮肤、眼睛接触以及吸入粉末、液体和喷雾。

Primary routes of exposure are skin, eye contact and inhalation of powders, liquids, and sprays.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

气管插管的麻醉动物通过空气喷射雾化器吸入药物溶液产生的液态气溶胶。气溶胶的质量中值空气动力学直径为2.81微米，几何标准偏差为2.53。阿米替林吸收50%所需的时间为1.3分钟。与之前报告的通过气管内注射0.1毫升药物溶液后测量的吸收速率进行比较，发现吸入气溶胶的药物吸收速度大约是气管内注射的两倍。

Anesthetized animals were allowed to inhale through a tracheal cannula liquid aerosols of drug solutions generated with an air-jet nebulizer. The aerosols had a mass median aerodynamic diameter of 2.81 um and a geometric standard deviation of 2.53. The time necessary for 50% absorption of amitrole was 1.3 min. Comparison with previously reported absorption rates measured after intratracheal injection of 0.1 mL of drug solution showed that drug inhaled as an aerosol was absorbed roughly 2 times more rapidly than when administered by intratracheal injection.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 职业暴露等级：
  C
• 职业暴露限值：
  TWA: 0.2 mg/m3
• TSCA：
  Yes
• 危险等级：
  9
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

制备方法与用途

化学性质
结晶固体，溶于水、甲醇、乙醇及氯仿，不溶于乙醚及丙酮。

用途
用作阳离子染料中间体，可合成多种红染料如阳离子红X-GRL；同时也是杂环中间体，可用于制药行业。此外，还可作为医药中间体用于合成唑嘧胺；亦可用作除草剂，特别适合作为棉花脱叶剂。

生产方法
由水合肼、氨基氰与甲酸经环合反应制得；或由氨基胍碳酸氢盐与甲酸作用后加热环合而成；也可采用硝酸胍作为原料，在5-15℃下与乙酸反应8小时，再与草酸作用，最后回流5小时环合成品。

类别
农药

毒性分级
中毒

急性毒性
大鼠口服LD₅₀：1100毫克/公斤；小鼠口服LD₅₀：14700毫克/公斤

可燃性危险特性
燃烧时产生有毒氮氧化物气体

储运特性
库房应保持通风、低温和干燥，与食品原料分开储存运输

灭火剂
干粉、泡沫或砂土

职业标准
时间加权平均容许浓度（TWA）为0.2毫克/立方米

反应信息

• 作为反应物：
  描述：

  3-氨基-1,2,4-三氮唑 在 亚膦酸 作用下， 生成 1H-1,2,4-三唑
  参考文献：
  名称：

  An Improved Procedure for the Deamination of 5-Aminotetrazole

  摘要：

  DOI：

  10.1021/ja01630a086
• 作为产物：
  描述：

  formylamino-guanidine; nitrate 在 sodium carbonate 作用下， 生成 3-氨基-1,2,4-三氮唑
  参考文献：
  名称：

  Thiele; Manchot, Justus Liebigs Annalen der Chemie, 1898, vol. 303, p. 54

  摘要：

  DOI：
• 作为试剂：
  描述：

  氰乙酸乙酯 、 邻硝基苯甲醛 在 3-氨基-1,2,4-三氮唑 作用下， 以 乙醇 为溶剂， 生成 2-cyano-3-(2-nitrophenyl)acrylic acid ethyl ester
  参考文献：
  名称：

  水性介质中三唑并[4,3-a]嘧啶的区域选择性绿色合成

  摘要：

  在氨基三唑，羰基化合物和α-氰基酯衍生物的多组分反应中研究了区域选择性，并使用微波或超声波在较短的时间内以优异的产率在水性介质中开发了三唑并嘧啶的独家合成方法。还讨论了反应的路径和机理。操作简便，环境友好的条件，目标产物的区域选择性形成，显着非常短的反应时间中的高收率是主要优点。

  DOI：

  10.2174/157017809787003124

文献信息

• [EN] THIOPHENE DERIVATIVES FOR THE TREATMENT OF DISORDERS CAUSED BY IGE<br/>[FR] DÉRIVÉS DE THIOPHÈNE POUR LE TRAITEMENT DE TROUBLES PROVOQUÉS PAR IGE
  申请人：UCB BIOPHARMA SRL

  公开号：WO2019243550A1

  公开（公告）日：2019-12-26

  Thiophene derivatives of formula (I) and a pharmaceutically acceptable salt thereof are provided. These compounds have utility for the treatment or prevention of disorders caused by IgE, such as allergy, type 1 hypersensitivity or familiar sinus inflammation.

  提供了公式（I）的噻吩衍生物及其药用可接受的盐。这些化合物对于治疗或预防由IgE引起的疾病具有用途，如过敏、1型超敏反应或家族性鼻窦炎。
• NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME
  申请人：Ryono Denis E.

  公开号：US20080009465A1

  公开（公告）日：2008-01-10

  Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure wherein is a heteroaryl ring; R 4 is —(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 ), —(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g , —(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g , —(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10 ), or —(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10 ); R 5 and R 6 are independently selected from H, alkyl and halogen; Y is R 7 (CH 2 ) s or is absent; and X, n, Z, m, R 4 , R 5 , R 6 , R 7 , and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.

  提供了磷酸酯和磷酸酯激活剂，因此在治疗糖尿病和相关疾病方面非常有用，并具有以下结构： 其中 是杂环芳基环； R 4 为—(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 )、—(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g 、—(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g 、—(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10) 或—(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10) ； R 5 和R 6 分别选择自H、烷基和卤素； Y为R 7 (CH 2 ) s 或不存在；以及 X、n、Z、m、R 4 、R 5 、R 6 、R 7 和s如本文所定义；或其药用盐。 还提供了一种利用上述化合物治疗糖尿病和相关疾病的方法。
• Antimicrobial and Anti-biofilm Activity of Thiourea Derivatives Bearing 3-amino-1H-1,2,4-triazole Scaffold
  作者：Joanna Stefanska、Karolina Stepien、Anna Bielenica、Daniel Szulczyk、Barbara Miroslaw、Anna E Koziol、Giuseppina Sanna、Filippo Iuliano、Silvia Madeddu、Michal Jozwiak、Marta Struga

  DOI：10.2174/1573406412666151204003146

  日期：2016.6.23

  3-amino-1H-1,2,4-triazole with the commercial aliphatic and aromatic isothiocyanates. The aliphatic isothiocyanate was used as reagent leading to substitution on NH atom of 3-aminotriazole ring, whereas the triazole amino group was substituted when isothiocyanate group was bonded to the Csp2 hybridized atom, e.g. an aryl or C=O fragment. All compounds were evaluated in vitro for the antimicrobial activity

  通过使3-氨基-1H-1,2,4-三唑与市售的脂族和芳族异硫氰酸酯反应，制得了21种硫脲衍生物。脂族异硫氰酸酯用作导致3-氨基三唑环的NH原子上取代的试剂，而当异硫氰酸酯基团键合至Csp2杂化原子，例如芳基或C ＝ O片段时，三唑氨基被取代。在体外评估所有化合物的抗微生物活性。衍生物1、2、4、8、9、10和12对革兰氏阳性球菌（金黄色葡萄球菌和表皮葡萄球菌）显示出最高的抑制作用。观察到的MIC值在4–32μg/ mL范围内。还测试了化合物对医院中耐金霉素的金黄色葡萄球菌菌株的体外抗菌活性。观察到的MIC值从4到64μg/ mL不等。产物4和10有效地抑制了耐甲氧西林和表皮葡萄球菌标准菌株的生物膜的形成。与对照相比，发现化合物10的IC50值为2–6μg/ mL更有希望。此外，评估了所有研究的硫脲对MT-4细胞的细胞毒性。化合物18具有明显的细胞毒性（CC50 = 8μM）。
• Synthesis and uncoupling activities of hydrophobic thioureas.
  作者：SEIJU KUBOTA、KISAKO HORIE、HEMANTK. MISRA、KOUHEI TOYOOKA、MASAYUKI UDA、MASAYUKI SHIBUYA、HIROSHI TERADA

  DOI：10.1248/cpb.33.662

  日期：——

  Various N-aryl-N'-phenylthioureas, N, N'-diarylthioureas and N-(1, 2, 4-triazol-3-yl)-N'-arylthioureas were prepared and examined for uncoupling activities. The results indicate that substitution at the 4-position of the phenyl groups of diaryl thioureas is very important for uncoupling activities. Diphenyl thioureas substituted with two or more halogen atoms exhibited strong activities. The highest activity was exhibited by a compound containing nitro groups on both phenyl groups. These results indicate that the hydrophobicity and acidic nature of the compound are of primary importance for uncoupling activities. A remarkable decrease in activity was observed with the thioureas which were substituted with pyridine and 1, 2, 4-triazole rings. The reaction of phenyl isothiocyanate with 3-amino-1, 2, 4-triazole was also studied.

  制备并测试了各种N-芳基-N'-苯基硫脲、N,N'-二芳基硫脲和N-(1,2,4-三唑-3-基)-N'-芳基硫脲的解偶联活性。结果表明，对于解偶联活性而言，二芳基硫脲的苯基4-位取代非常重要。含有两个或更多卤素原子的二苯基硫脲表现出强烈的活性。在两个苯基上都含有硝基的化合物显示出最高的活性。这些结果表明，化合物对疏水性和酸性对于解偶联活性具有首要重要性。当硫脲被吡啶和1,2,4-三唑环取代时，活性显著下降。还研究了苯基异硫氰酸酯与3-氨基-1,2,4-三唑的反应。
• Regioselective synthesis of pyrimido[5,4-c][2,1]benzothiazines by reactions of β-chloroaldehydes with n-c-n binucleophiles
  作者：Kirill Popov、Tatyana Volovnenko、Alexander Turov、Yulian Volovenko

  DOI：10.1002/jhet.271

  日期：——

  The method of pyrimidine ring fusion at the [c] side of benzothiazines based on the reaction of their chloroaldehyde derivatives with amidines is described. Formation of the structural isomers of reaction products was investigated, and regioselectivity of heterocyclization reactions was shown. A number of novel pyrimidobenzothiazines were synthesized. J. Heterocyclic Chem., 2010.

  描述了基于苯并噻嗪的氯醛衍生物与am的反应在嘧啶环的[ c ]侧进行嘧啶环稠合的方法。研究了反应产物的结构异构体的形成，并显示了杂环化反应的区域选择性。合成了许多新颖的嘧啶并苯并噻嗪。J.杂环化​​学.2010。

表征谱图