甲胍 | 471-29-4

• 物质功能分类: 化学试剂 - 有机试剂 - 胍盐
• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 甲胍
• 中文别名: 甲基胍
• 英文名称: 1-methylguanidine
• 英文别名: methylguanidine；N-methyl-guanidine
• CAS: 471-29-4
• 化学式: C₂H₇N₃
• 分子量: 73.0977
• InChiKey: CHJJGSNFBQVOTG-UHFFFAOYSA-N

物化性质

• 熔点：
  180-200℃
• 沸点：
  96℃
• 密度：
  1.19
• 闪点：
  12℃
• 物理描述：
  Solid
• 溶解度：
  0.02 M

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  5
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  1

ADMET

代谢

尿素毒素往往会因为饮食过量或者肾脏过滤功能不佳而在血液中积聚。大多数尿素毒素是代谢废物，通常通过尿液或粪便排出。

Uremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

尿毒症毒素如甲基胍通过有机离子转运体（特别是OAT3）积极运输到肾脏中。尿毒症毒素水平的增加可以刺激活性氧种类的产生。这似乎是通过尿毒症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被称为KLOTHO的蛋白质。KLOTHO已被确定在抗衰老、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和蛋白质水平会降低（A7869）。

Uremic toxins such as methylguanidine 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

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

长期暴露于尿毒症毒素可能会导致多种疾病，包括肾脏损伤、慢性肾病和心血管疾病。

Chronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

内源性的，摄入，皮肤（接触）

Endogenous, Ingestion, Dermal (contact)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

作为尿毒症毒素，这种化合物可以引起尿毒症综合征。尿毒症综合征可能影响身体的任何部位，并可能导致恶心、呕吐、食欲丧失和体重减轻。它还可能引起精神状态的变化，如混乱、意识减退、躁动、精神疾病、癫痫和昏迷。还可能出现异常出血，例如在非常轻微的损伤后自发或大量出血。心脏问题，如心律不齐、心脏包膜（心包炎）炎症和心脏压力增加，也可能出现在尿毒症综合征患者身上。由于肺部和胸壁之间（胸腔积液）的液体积聚导致的呼吸急促也可能出现。

As a uremic toxin, this compound can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.

来源:Toxin and Toxin Target Database (T3DB)

安全信息

• 储存条件：
  | 室温 |

反应信息

• 作为反应物：
  描述：

  甲胍 在 N,N-二甲基磺酰胺 作用下， 以 二甲基亚砜 为溶剂， 生成 N¹-Methyl-N³-sulfamoylguanidin
  参考文献：
  名称：

  Sulfamylguanidines

  摘要：

  DOI：

  10.1021/jo01038a510
• 作为产物：
  描述：

  methyl carbonimidodithioic acid dimethyl ester 在 乙醇 、 氨 作用下， 生成 甲胍
  参考文献：
  名称：

  Schenck, Archiv der Pharmazie, 1911, vol. 249, p. 469

  摘要：

  DOI：
• 作为试剂：
  描述：

  二硫化碳 在 甲胍 作用下， 以 水 、 丙酮 为溶剂， 生成 三硫代碳酸
  参考文献：
  名称：

  Moharir,Y.E., Indian Journal of Chemistry, 1974, vol. 12, p. 490 - 492

  摘要：

  DOI：

文献信息

• CuI-Catalyzed Amination of Arylhalides with Guanidines or Amidines: A Facile Synthesis of 1-<i>H</i>-2-Substituted Benzimidazoles
  作者：Xiaohu Deng、Heather McAllister、Neelakandha S. Mani

  DOI：10.1021/jo900912h

  日期：2009.8.7

  CuI/L5 (N,N′-dimethylethylenediamine) proves to be an efficient catalyst system for the amination of arylhalides with guanidines. The same catalyst system is then successfully applied to the one-step synthesis of 1-H-2-amino-benzimidazoles through tandem aminations of 1,2-dihaloarenes in modest yields. This methodology is also applicable for the preparation of 1-H or 1-substutituted 2-aryl- or 2-alkyl-benzimidazoles

  事实证明，CuI / L5（N，N'-二甲基乙二胺）是一种用于将芳基卤化物与胍胺化的有效催化剂体系。然后将相同的催化剂体系成功地通过1,2-二卤代芳烃的串联胺化以适度的产率成功地一步合成1- H -2-氨基-苯并咪唑。该方法学也可用于制备1- H或1-取代的2-芳基-或2-烷基-苯并咪唑。
• [EN] MLKL INHIBITORS<br/>[FR] INHIBITEURS MLKL
  申请人：NAT INSTITUTE OF BIOLOGICAL SCIENCES BEIJING

  公开号：WO2018157800A1

  公开（公告）日：2018-09-07

  Purine derivatives that inhibit cellular necroptosis and/or human MLKL, pharmaceutical compositions thereof, and methods of treating an MLKL-mediated disorder with an effective amount of the compound or composition. Said MLKL-mediated disorder is pathology associated necroptosis, including ischemia-reperfusion damage, neurodegeneration, and inflammatory diseases such as acute pancreatitis, multiple sclerosis, inflammatory bowel disease, and allergic colitis.

  嘌呤衍生物，用于抑制细胞坏死性凋亡和/或人类MLKL；包含该衍生物的药物组合物；以及使用有效量的该化合物或组合物治疗MLKL介导的疾病的方法。所述MLKL介导的疾病是与坏死性凋亡相关的病理学，包括缺血再灌注损伤、神经退行性疾病、以及诸如急性胰腺炎、多发性硬化症、炎症性肠病和过敏性结肠炎等炎症性疾病。
• A STUDY OF THE REACTIONS OF AMMONIUM SULPHAMATE WITH AMIDES AND UREAS
  作者：Paul E. Gagnon、Jean L. Boivin、Catherine Haggart

  DOI：10.1139/v56-214

  日期：1956.11.1

  The preparation of nitriles from amides and ammonium sulphamate was investigated. The method was found to be generally applicable and good yields were obtained in most cases. The mechanism of the reaction involved the liberation of ammonia and the formation of ammonium N-carbonyl sulphamates, which decomposed into nitriles and ammonium bisulphate.The mechanism for the formation of guanidine and cyanuric acid from ureas was elucidated. The effects of methyl, phenyl, acetyl, and benzoyl groups on the reactivity of the urea molecule were determined. Methylamine and aniline were obtained from methylurea and phenylurea together with guanidine and cyanuric acid. Acetylurea and benzoylurea formed acetonitrile and benzonitrile, the yield of guanidine being low but that of cyanuric acid very high.

  从酰胺和硫酸铵磺酸酯制备腈类化合物的方法进行了研究。该方法被发现通常适用，并且在大多数情况下获得了良好的产率。反应的机理涉及氨的释放和铵N-羰基磺酸酯的形成，后者分解为腈类化合物和硫酸氢铵。从尿素中形成胍和异三聚氰酸的机理得到了阐明。确定了甲基、苯基、乙酰基和苯甲酰基对尿素分子反应性的影响。从甲基脲和苯基脲中获得了甲胺和苯胺，以及胍和异三聚氰酸。乙酰脲和苯甲酰脲形成乙腈和苯腈，胍的产率较低，但异三聚氰酸的产率非常高。
• Second-Generation Phenylthiazole Antibiotics with Enhanced Pharmacokinetic Properties
  作者：Mohammed A. Seleem、Ahmed M. Disouky、Haroon Mohammad、Tamer M. Abdelghany、Ahmed S. Mancy、Sammar A. Bayoumi、Ahmed Elshafeey、Ahmed El-Morsy、Mohamed N. Seleem、Abdelrahman S. Mayhoub

  DOI：10.1021/acs.jmedchem.6b00233

  日期：2016.5.26

  first-generation members with a cyclic, unhydrolyzable pyrimidine ring. The hydrazide-containing analogue 17 was identified as the most potent analogue constructed thus far. The corresponding amine 8 was 8 times less active. Finally, incorporating the nitrogenous side chain within an aromatic system completely abolished the antibacterial character. Replacement of the n-butyl group with cyclic bioisosteres revealed

  合成了一系列第二代2-（1-（2-（4-丁基苯基）-4-甲基噻唑-5-基）亚乙基）氨基胍（1）的类似物，并针对耐甲氧西林的金黄色葡萄球菌（MRSA）进行了测试。 。设计这些化合物的目的是改善药代动力学性质。通过用环状的不可水解的嘧啶环取代第一代成员的可快速水解的席夫碱部分来实现该主要目的。含酰肼的类似物17被确定为迄今为止构建的最有效的类似物。相应的胺8活跃度降低了8倍。最后，将含氮侧链并入芳族体系中完全消除了抗菌特性。用环状生物等排体取代正丁基可显示出环己烯基类似物29，该化合物在体外抗MRSA效能方面表现出显着改善。增大或减小环的尺寸会使抗菌活性变差。化合物17表现出优异的体外和体内药代动力学特性，提供了令人信服的证据证明这种特定的类似物是值得进一步分析的良好候选药物。
• Discovery and initial optimization of 5,5′-disubstituted aminohydantoins as potent β-secretase (BACE1) inhibitors
  作者：Pawel Nowak、Derek C. Cole、Ann Aulabaugh、Jonathan Bard、Rajiv Chopra、Rebecca Cowling、Kristi Y. Fan、Baihua Hu、Steve Jacobsen、Minakshi Jani、Guixan Jin、Mei-Chu Lo、Michael S. Malamas、Eric S. Manas、Rani Narasimhan、Peter Reinhart、Albert J. Robichaud、Joseph R. Stock、Joan Subrath、Kristine Svenson、Jim Turner、Erik Wagner、Ping Zhou、John W. Ellingboe

  DOI：10.1016/j.bmcl.2009.11.052

  日期：2010.1

  8,8-Diphenyl-2,3,4,8-tetrahydroimidazo[1,5-a]pyrimidin-6-amine (1) was identified through HTS, as a weak (micromolar) inhibitor of BACE1. X-Ray crystallographic studies indicate the 2-aminoimidazole ring forms key H-bonding interactions with Asp32 and Asp228 in the catalytic site of BACE1. Lead optimization using structure-based focused libraries led to the identification of low nanomolar BACE1 inhibitors

  通过HTS将8,8-二苯基-2,3,4,8-四氢咪唑并[1,5- a ]嘧啶-6-胺（1）鉴定为BACE1的弱（微摩尔）抑制剂。X射线晶体学研究表明2-氨基咪唑环在BACE1的催化位点与Asp32和Asp228形成关键的H键相互作用。使用基于结构的聚焦库进行的前导优化导致鉴定出具有从S 1到S 3口袋的取代基的低纳摩尔BACE1抑制剂（例如20b）。

表征谱图