胍 | 113-00-8

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 胍
• 中文别名: 十八醇；亚氨脲
• 英文名称: guanidine nitrate
• 英文别名: GUANIDINE
• CAS: 113-00-8
• 化学式: CH₅N₃
• mdl: MFCD00044535
• 分子量: 59.0708
• InChiKey: ZRALSGWEFCBTJO-UHFFFAOYSA-N

物化性质

• 熔点：
  ~50°
• 沸点：
  82.3°C (rough estimate)
• 密度：
  1.6000 (rough estimate)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）
• 物理描述：
  Deliquescent solid; Absorbs carbon dioxide from the air; [Merck Index]
• 颜色/状态：
  Deliquescent crystalline mass
• 蒸汽压力：
  2.2 mm Hg at 25 °C (est)
• 亨利常数：
  Henry's Law constant = 2.34X10-11 atm-cu m/mol at 25 °C (est)
• 分解：
  When heated to decomposition it emits toxic fumes of /Nitrogen oxide/.
• 解离常数：
  12.5

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  4
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  75.9
• 氢给体数：
  3
• 氢受体数：
  1

ADMET

代谢

未代谢。

Not metabolized.

来源:DrugBank

代谢

未代谢。 半衰期：7-8小时

Not metabolized. Half Life: 7-8 hours

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

尿素毒素如胍类物质通过有机离子转运体（特别是OAT3）被积极运输到肾脏中。尿素毒素水平的升高可以刺激活性氧种类的产生。这似乎是通过尿素毒素直接结合或抑制NADPH氧化酶（特别是肾脏和心脏中丰富的NOX4）来介导的（A7868）。活性氧种类可以诱导几种不同的DNA甲基转移酶（DNMTs），这些酶参与沉默一种名为KLOTHO的蛋白质。KLOTHO被识别为在抗衰老、矿物质代谢和维生素D代谢中具有重要作用。许多研究表明，在急性或慢性肾脏疾病中，由于局部活性氧种类水平升高，KLOTHO mRNA和蛋白水平会降低（A7869）。

Uremic toxins such as guaniidine are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (A7868). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (A7869).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 药物性肝损伤

化合物：胍

Compound:guanidine

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI标注：模糊的DILI关注

DILI Annotation:Ambiguous DILI-concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

严重性等级：3

Severity Grade:3

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

不良反应部分

Label Section:Adverse reactions

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

迅速吸收和分布

Rapidly absorbed and distributed

来源:DrugBank

吸收、分配和排泄

特定胍化合物的积累（GCs）与肾衰竭的神经学、心血管、血液学和免疫学并发症有关...在年龄最大的杂合子和较年轻的纯合子多囊肾病（PKD）大鼠的血液中，尿素、胍丁酸、肌酐、胍、甲基胍和N(G)N(G)-亚甲基精氨酸（对称亚甲基精氨酸）的明显增加与研究中的人类PKD群体中发现的水平大致相同，特别是在肾小球滤过率低于60 mL/min/1.73 sq m的患者中。在纯合子和年龄最大的杂合子PKD/Mhm大鼠的终末期肾疾病中观察到的血浆胍乙酸水平降低也在肾小球滤过率低于20 mL/min/1.73 sq m的患者的血清中观察到.../胍化合物/

Accumulation of specific guanidine compounds (GCs) has been related to neurological, cardiovascular, hematological, and immunological complications of renal failure ... The obvious increases of urea, guanidinosuccinic acid, creatinine, guanidine, methylguanidine, and N(G)N(G)-dimethylarginine (symmetrical dimethylarginine) seen in blood of oldest heterozygous and younger homozygous polycystic kidney disease (PKD) rats were largely within the same range as those found in the studied human PKD population, especially in patients with a glomerular filtration rate below 60 mL/min/1.73 sq m. The decreased levels of plasma guanidinoacetic acid seen at end-stage renal disease in homozygous and oldest heterozygous PKD/Mhm rats were also observed in serum of patients with a glomerular filtration rate below 20 mL/min/1.73 sq m ... /Guanidino compounds/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

刷状缘膜囊泡是从捐赠者的人类肾脏中制备的...通过快速过滤法测定，在存在向外定向的质子梯度的条件下，(14)C-胍...在囊泡中的摄取量在所有早期时间点都显著高于不存在梯度时的摄取量...获得的证据表明，胍的转运体与之前描述的用于TEA的有机阳离子质子逆向转运体不同。/四乙基铵/

Brush-border membrane vesicles were prepared from donor human kidneys ... Uptake of (14)C-guanidine ... in the vesicles, as determined by rapid filtration, was significantly greater in the presence of an outwardly-directed proton gradient, at all early time points, than in the absence of the gradient ... Evidence was obtained suggesting that the transporter for guanidine is distinct from the previously described organic cation proton antiporter for TEA. /Tetraethylammonium/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

肾皮质刷状缘膜囊泡中胍丁胺的摄取特征在兔肾皮质中被研究。胍丁胺的摄取明显受到向外方向的H+梯度的刺激，导致短暂的逆向运输。这种刺激不是由于内向负的H+扩散电位，因为离子载体诱导的H+扩散电位和K+扩散电位（都是内向负）未能增强胍丁胺的摄取。H+梯度本身似乎是摄取的驱动力...

The characteristics of guanidine uptake in brush-border membrane vesicles isolated from rabbit renal cortex were investigated. Guanidine uptake was markedly stimulated by an outwardly directed H+ gradient, resulting in a transient uphill transport. This stimulation was not due to an inside-negative, H+-diffusion potential because an ionophore-induced H+-diffusion potential and a K+-diffusion potential (both inside-negative) failed to enhance guanidine uptake. The H+ gradient itself appeared to be the driving force for the uptake ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

30名血液透析患者和15名未进行血液透析的慢性肾衰竭患者的血浆、红细胞和尿液中胍基化合物的浓度被测定。慢性肾衰竭患者（无论是否进行血液透析）的血浆牛磺酸、胍基琥珀酸、α-N-乙酰-L-精氨酸、肌酸、胍基丁酸、胍和甲基胍的水平显著升高。相比之下，血浆胍乙酸浓度显著降低。红细胞的肌酐、胍基琥珀酸、胍和甲基胍浓度也显著升高。血浆肌酐浓度与红细胞胍基琥珀酸或甲基胍浓度之间没有观察到相关性。然而，血浆和红细胞甲基胍之间存在显著相关性，以及血浆和红细胞胍基琥珀酸之间也存在显著相关性。

... The plasma, erythrocyte, and urinary concentration of guanidino compounds in 30 hemodialysis patients and 15 patients with chronic renal failure who had not undergone hemodialysis /were determined/ ... Plasma levels of taurocyamine, guanidinosuccinic acid, alpha-N-acetyl-L-arginine, creatine, guanidinobutyric acid, guanidine, and methylguanidine were significantly increased in patients with chronic renal failure with or without hemodialysis. In contrast, plasma guanidinoacetic acid concentrations were significantly decreased. Erythrocyte concentrations of creatinine, guanidinosuccinic acid, guanidine and methylguanidine were also markedly elevated. No correlation was observed between plasma creatinine concentration and erythrocyte concentration of guanidinosuccinic acid or methylguanidine. However, there was a significant correlation between plasma and erythrocyte methylguanidine, and between plasma and erythrocyte guanidinosuccinic acid. /Guanidino compounds/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  8
• 危险品运输编号：
  UN 1759
• 包装等级：
  II

制备方法与用途

化学性质
无色结晶状，熔点约为50℃。极易溶于水和醇。具有潮解性，并容易从空气中吸收二氧化碳，呈现强碱性。加热至160℃时会分解为三聚氰胺和氨。

用途
主要用于有机合成中间体，特别在制造磺胺药物和染料方面应用广泛。由于游离胍难以分离，通常以盐类形式存在，如盐酸胍、硝酸胍、碳酸胍及硫酸胍等。

生产方法
可由氰氨化钙与碘化铵作用或尿素与氨在加压条件下反应制得。

反应信息

• 作为反应物：
  描述：

  胍 生成 碳酸胍
  参考文献：
  名称：

  Marckwald; Struwe, Chemische Berichte, 1922, vol. 55, p. 462

  摘要：

  DOI：
• 作为产物：
  描述：

  氯化苦 在 乙醇 、 氨 作用下， 生成 胍
  参考文献：
  名称：

  Hofmann, Justus Liebigs Annalen der Chemie, 1866, vol. 139, p. 112

  摘要：

  DOI：
• 作为试剂：
  描述：

  methyl 7-(2-hydroxy-5-oxocyclopent-3-enyl)heptanoate 在 胍 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 phosphate buffer 、 乙醚 为溶剂， 反应 66.0h， 生成 (-)-methyl 7-[(1S,2R)-2-hexyl-5-oxocyclopent-3-enyl]heptanoate
  参考文献：
  名称：

  对映体纯 (1R,2S,5S)- 和 (1S,2R,5R)-罗沙前列醇甲酯的有效合成

  摘要：

  我们报告了罗沙前列醇的对映体纯 1,2- TRANS-1,5- CIS-甲基酯的简明合成，罗沙前列醇是一种用于治疗胃和十二指肠溃疡的前列腺素衍生物，使用化学和立体选择性迈克尔作为关键步骤将格氏试剂添加到未保护的羟基环戊烯酮中。

  DOI：

  10.1055/s-2007-982558

文献信息

• BENZOTHIOPHENE INHIBITORS OF RHO KINASE
  申请人：Kahraman Mehmet

  公开号：US20080021026A1

  公开（公告）日：2008-01-24

  The present invention relates to compounds and methods which may be useful as inhibitors of Rho kinase for the treatment or prevention of disease.

  本发明涉及化合物和方法，这些化合物和方法可能作为Rho激酶的抑制剂在治疗或预防疾病方面有用。
• [EN] PYRAZOLE DERIVATIVES USEFUL AS INHIBITORS OF FAAH<br/>[FR] DÉRIVÉS DE PYRAZOLE UTILES COMME INHIBITEURS DE FAAH
  申请人：MERCK & CO INC

  公开号：WO2009151991A1

  公开（公告）日：2009-12-17

  The present invention is directed to certain imidazole derivatives which are useful as inhibitors of Fatty Acid Amide Hydrolase (FAAH). The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer disease, and Parkinson's disease

  本发明涉及某些咪唑衍生物，其可用作脂肪酰胺水解酶（FAAH）的抑制剂。该发明还涉及包含这些化合物作为活性成分的药物配方，以及这些化合物及其配方在治疗某些疾病中的使用，包括骨关节炎、类风湿性关节炎、糖尿病神经病变、带状疱疹后神经痛、骨骼肌肉疼痛和纤维肌痛，以及急性疼痛、偏头痛、睡眠障碍、阿尔茨海默病和帕金森病。
• [EN] INHIBITORS OF GLYCINAMIDE RIBONUCLEOTIDE TRANSFORMYLASE<br/>[FR] INHIBITEURS DE LA TRANSFORMYLASE DE LA GLYCINAMIDE RIBONUCLEOTIDE
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2003087065A1

  公开（公告）日：2003-10-23

  Potent human inhibitors of human glycinamide ribonucleotide transformylase and of aminoimidazole carboxamide ribonucleotide transformylase are designed, synthesized, and characterized.

  设计、合成和表征了对人类甘氨酰核糖核苷转甲基酶和氨基咪唑甲酰核糖核苷转甲基酶具有强效抑制作用的人类抑制剂。
• 2,4-diamino-5-(1,2,3,4-tetrahydro-(substituted or
  申请人：Burroughs Wellcome Co.

  公开号：US04587341A1

  公开（公告）日：1986-05-06

  Compounds of the formula (II) ##STR1## or a salt, N-oxide or acyl derivative thereof, wherein Y is a group ##STR2## which is optionaly substituted and which optionally contain a nitrogen atom at one of positions A, B, C, D or E, in which the dotted line represents aromatic rings unless one of the rings contains a nitrogen atom in which case this ring is either aromatic or partially saturated, have antimicrobial properties. Processes for making these compounds, pharmaceutical compositions containing them and the medical use of the compounds are also disclosed.

  式（II）的化合物##STR1##或其盐、N-氧化物或酰基衍生物，其中Y是一个组##STR2##，可选择地被取代，并且可选择地在位置A、B、C、D或E之一含有氮原子，在这些位置中的虚线代表芳香环，除非其中一个环含有氮原子，在这种情况下，该环要么是芳香的，要么是部分饱和的，具有抗微生物特性。还公开了制备这些化合物的方法、含有它们的药物组合物以及这些化合物的医药用途。
• 2-Benzazepines. 5. Synthesis of pyrimido[5,4-d][2]benzazepines and their evaluation as anxiolytic agents
  作者：Eugene J. Trybulski、Louis E. Benjamin、James V. Earley、R. Ian Fryer、Norman W. Gilman、Earl Reeder、Armin Walser、Arnold B. Davidson、W. Dale Horst

  DOI：10.1021/jm00365a008

  日期：1983.11

  A series of 5H-pyrimido[5,4-d][2]benzazepines has been synthesized, starting from the corresponding 2-benzazepin-5-ones, and evaluated as potential anxiolytic agents. Selected compounds from this series show a pharmacological profile of action different than that of diazepam. They are more potent than diazepam in the anti-pentylenetetrazole test and in the [3H]diazepam binding assay, yet show less

  从相应的2-苯并ze庚因-5-酮开始，合成了一系列5H-嘧啶并[5,4-d] [2]苯并ze庚因，并被评估为潜在的抗焦虑药。从该系列中选择的化合物显示出与地西epa不同的药理作用。在抗戊烯四唑试验和[3H]地西ze结合试验中，它们比地西epa更有效，但在斜筛试验中却显示出较小的活​​性。给出了9-氯-7-（2-氯苯基）-5H-嘧啶[5,4-d] [2]苯并ze庚因（7c）的药理数据。讨论了这些潜在抗焦虑剂的构效关系。

表征谱图