盐酸阿米洛利 | 2016-88-8

• 物质功能分类: 原料药 - 泌尿系统用药 - 利尿药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 盐酸阿米洛利
• 中文别名: 阿米洛利；阿米洛利盐酸盐水合物；N-脒基-3,5-二氨基-6-氯吡嗪甲酰胺盐酸盐；氨氯吡咪；盐酸氨氯吡咪
• 英文名称: amiloride hydrochloride
• 英文别名: Amiloridhydrochlorid；N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride；[Amino-[(3,5-diamino-6-chloropyrazine-2-carbonyl)amino]methylidene]azanium;chloride；[amino-[(3,5-diamino-6-chloropyrazine-2-carbonyl)amino]methylidene]azanium;chloride
• CAS: 2016-88-8
• 化学式: C₆H₈ClN₇O*ClH
• 分子量: 266.09
• InChiKey: ACHKKGDWZVCSNH-UHFFFAOYSA-N

物化性质

• 熔点：
  293-294°C
• 溶解度：
  在水中的溶解度50 mg/mL，澄清，黄绿色
• 物理描述：
  Amiloride hydrochloride appears as crystalline solid or very light yellow powder. (NTP, 1992)
• 碰撞截面：
  145.7 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]
• 稳定性/保质期：

  如果按照规定使用和储存，则不会发生分解，没有已知的危险反应，应避免接触氧化物。

计算性质

• 辛醇/水分配系数(LogP)：
  -0.87
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  159
• 氢给体数：
  5
• 氢受体数：
  5

安全信息

• 危险等级：
  6.1(a)
• 危险品标志：
  T
• 安全说明：
  S36,S45
• 危险类别码：
  R25
• WGK Germany：
  3
• 海关编码：
  29339980
• 危险品运输编号：
  UN 2811 6.1/PG 3
• RTECS号：
  UQ2275500
• 包装等级：
  II
• 危险类别：
  6.1(a)
• 储存条件：
  请将贮藏器保持密封，并存放在阴凉、干燥处。确保工作环境有良好的通风或排气设施。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Amiloride HCl dihydrate
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H301: Toxic if swallowed
P264: Wash thoroughly after handling
P270: Do not eat, drink or smoke when using this product
P301+P310: IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician
P321: Specific treatment (see on this label)
P405: Store locked up

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Section 3. Composition/information on ingredients.
Ingredient name: Amiloride HCl dihydrate
CAS number: 2016-88-8

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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.
Storage: Store in closed vessels.

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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
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C6H8ClN7O.ClH.2H2O
Molecular weight: 302.1

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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, hydrogen chloride.

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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
UN Number: UN2811 Class: 6.1 Packing group: III
Proper shipping name: TOXIC SOLIDS, ORGANIC, N.O.S. (Amiloride HCl dihydrate)

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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

制备方法与用途

生物活性

Amiloride (MK-870) 是一种选择性的T-type钙通道阻滞剂、上皮钠通道（ENaC）阻滞剂以及尿激酶纤溶酶原激活剂(uPA)抑制剂，Ki值为7 μM。

靶点

Target	Value
氯化钠通道
T-type钙通道
uPA	7 μM (Ki)

体外研究

Amiloride 是上皮钠通道（ENaC）的相对选择性抑制剂，IC50值范围为0.1 μM至0.5 μM。它对钠/氢交换器(NHE)的抑制作用较差，在低外部钠离子浓度时IC50可低至3 μM，在高外部钠离子浓度时IC50高达1 mM。Amiloride 对钠/钙交换（NCX）具有弱抑制作用，IC50值为1 mM。在血管平滑肌细胞中，Amiloride 完全抑制了钠离子内流，并通过阻断ENaC蛋白质的活性抑制生肌响应于增加的灌注压力。

体内研究

在DOCA盐诱导的高血压大鼠模型中，Amiloride（1 mg/kg/天，皮下注射）逆转了初始胶原沉积的增加并防止进一步增加。在饮用高盐水、具有中风倾向的自发性高血压大鼠（SHRSP）中，Amiloride 延迟了蛋白尿的发生，并改善了脑和肾组织学分数。此外，在高血压盐依赖性动物模型中，Amiloride 拮抗或阻止醛固酮在这些细胞以及血管和肾脏组织中的作用。

化学性质

Amiloride 是一种黄色或绿黄色粉末状物质，熔点为293.5℃，易溶于水且几乎无臭。其结构与氨氯吡咪碱相似[2609-46-3]，熔点为240.5-241.5℃。

用途

Amiloride 是一种弱效利尿剂，作用类似于氨苯蝶啶，在目前的排钠甾钾利尿药中具有最强的作用。

反应信息

• 作为反应物：
  描述：

  盐酸阿米洛利 在 N-碘代丁二酰亚胺 、 palladium on activated charcoal 、 氢气 、 magnesium oxide 作用下， 生成 N-amidino-3,5-diamino-6-iodo-2-pyrazinecarboxamide hydrochloride
  参考文献：
  名称：

  Synthesis and preliminary evaluation of amiloride analogs as inhibitors of the urokinase-type plasminogen activator (uPA)

  摘要：

  A known side-activity of the oral potassium-sparing diuretic drug amiloride is inhibition of the enzyme urokinase-type plasminogen activator (uPA, K-i = 7 mu M), a promising anticancer target. Several studies have demonstrated significant antitumor/metastasis properties for amiloride in animal cancer models and it would appear that these arise, at least in part, through inhibition of uPA. Selective optimization of amiloride's structure for more potent inhibition of uPA and loss of diuretic effects would thus appear as an attractive strategy towards novel anticancer agents. The following report is a preliminary structure-activity exploration of amiloride analogs as inhibitors of uPA. A key finding was that the well-studied 5-substituted analogs ethylisopropyl amiloride (EIPA) and hexamethylene amiloride (HMA) are approximately twofold more potent than amiloride as uPA inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.044

文献信息

• Alpha2C adrenoreceptor agonists
  申请人：McCormick D. Kevin

  公开号：US20070093477A1

  公开（公告）日：2007-04-26

  In its many embodiments, the present invention relates to a novel class of phenylmorpholine and phenylthiomorpholine compounds useful as α2C adrenergic receptor agonists, pharmaceutical compositions containing the compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the α2C adrenergic receptor agonists using such compounds or pharmaceutical compositions.

  在其多种实施形式中，本发明涉及一类新型的苯基吗啡啶和苯基硫代吗啡啶化合物，这些化合物可用作α2C肾上腺素受体激动剂，包含这些化合物的药物组合物，以及使用这些化合物或药物组合物治疗、预防、抑制或改善与α2C肾上腺素受体激动剂相关的一种或多种疾病的方法。
• [EN] FUMAGILLOL COMPOUNDS AND METHODS OF MAKING AND USING SAME<br/>[FR] COMPOSÉS DE FUMAGILLOL, ET LEURS PROCÉDÉS DE FABRICATION ET D'UTILISATION
  申请人：ZAFGEN INC

  公开号：WO2018031877A1

  公开（公告）日：2018-02-15

  Disclosed herein, in part, are fumagillol compounds and methods of use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making fumagillol compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.

  本文披露了富马醇类化合物及其在治疗医学疾病（如肥胖症）中的用途方法。提供了富马醇类化合物的药物组合物和制备方法。这些化合物被认为对蛋氨酸氨肽酶2具有活性。
• [EN] FACTOR XIa INHIBITORS<br/>[FR] INHIBITEURS DU FACTEUR XIA
  申请人：MERCK SHARP & DOHME

  公开号：WO2017074832A1

  公开（公告）日：2017-05-04

  The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma Kallikrein.

  本发明提供了一种化合物（I）的化合物，以及包含一种或多种所述化合物的药物组合物，并且提供了使用所述化合物用于治疗或预防血栓形成、栓塞、高凝血性或纤维变化的方法。这些化合物是选择性因子XIa抑制剂或因子XIa和血浆激肽酶的双重抑制剂。
• [EN] COMPOSITIONS FOR USE IN TREATING PULMONARY ARTERIAL HYPERTENSION<br/>[FR] COMPOSITIONS UTILISÉES POUR TRAITER L'HYPERTENSION ARTÉRIELLE PULMONAIRE
  申请人：PELOTON THERAPEUTICS INC

  公开号：WO2016145032A1

  公开（公告）日：2016-09-15

  The present disclosure provides methods of treating pulmonary arterial hypertension (PAH) in a subject in need thereof. Compositions for use in these methods are also provided.

  本公开提供了治疗需要的受试者肺动脉高压（PAH）的方法。还提供了用于这些方法的组合物。
• [EN] NATRIURETIC PEPTIDE RECEPTOR A AGONISTS USEFUL FOR THE TREATMENT OF CARDIOMETABOLIC DISEASES, KIDNEY DISEASE AND DIABETES<br/>[FR] AGONISTES DU RÉCEPTEUR A DU PEPTIDE NATRIURÉTIQUE UTILES POUR LE TRAITEMENT DE MALADIES CARDIOMÉTABOLIQUES, D'UNE MALADIE RÉNALE ET DU DIABÈTE
  申请人：MERCK SHARP & DOHME

  公开号：WO2020236688A1

  公开（公告）日：2020-11-26

  The present invention relates to Compounds of Formula I: I and pharmaceutically acceptable salts or prodrug thereof. The present invention also relates to compositions comprising at least one compound of Formula I, and methods of using the compounds of Formula I for treatment of cardiometabolic diseases including high blood pressure, heart failure, kidney disease, and diabetes in a subject.

  本发明涉及公式I的化合物：I及其药用可接受的盐或前药。本发明还涉及包含至少一种公式I化合物的组合物，以及使用公式I化合物治疗心脏代谢疾病，包括高血压、心力衰竭、肾脏疾病和糖尿病的方法。