66376-36-1

• 常用中文名：阿仑膦酸
• 常用英文名：Alendronic acid
• CAS号：66376-36-1
• 分子式：C₄H₁₃NO₇P₂
• 分子量：249.09600
• 相关类别： 原料药 水、电解质及酸碱平衡调节药 电解质平衡调节药
• 发布时间：2018-09-01 07:33:59
• 更新时间：2024-01-06 22:21:39
• Alendronic acid,一种双膦酸盐,是法呢基二磷酸合酶 (FDPS) 抑制剂。Alendronic acid 抑制破骨细胞介导的骨吸收。Alendronic acid 对绝经后骨质疏松症,恶性高钙血症和 Paget 病具有疗效。

名称

• 中文名: 阿仑膦酸
• 英文名: alendronic acid
• 中文别名: 阿仑磷酸; 4-氨基-1-羟基丁亚基-1,1-二磷酸; (4-氨基-1-羟基亚丁基)双磷酸
• 英文别名: (4-Amino-1-hydroxybutane-1,1-diyl)diphosphonic acid; (4-amino-1-hydroxy-1-phosphonobutyl)phosphonic acid

物化性质

• 密度: 1.857 g/cm3
• 沸点: 616.7ºC at 760 mmHg
• 熔点: 230-235ºC
• 分子式: C₄H₁₃NO₇P₂
• 分子量: 249.09600
• 闪点: 326.7ºC
• 精确质量: 249.01700
• PSA: 180.93000
• 外观性状: 白色结晶粉末
• 储存条件:

  存放在密封容器内，并放在阴凉，干燥处。储存的地方必须远离氧化剂。

• 稳定性:

  常温常压下稳定，远离氧化剂。

• 水溶解性: 水溶性：不溶
• 分子结构:

  1、 摩尔折射率：45.50

  2、 摩尔体积（cm³/mol）：134.1

  3、 等张比容（90.2K）：443.2

  4、 表面张力（dyne/cm）：119.3

  5、 极化率（10^-24cm³）：18.03

• 计算化学:

  1、 疏水参数计算参考值（XlogP）：-6.5

  2、 氢键供体数量：6

  3、 氢键受体数量：8

  4、 可旋转化学键数量：5

  5、 拓扑分子极性表面积（TPSA）：161

  6、 重原子数量：14

  7、 表面电荷：0

  8、 复杂度：257

  9、 同位素原子数量：0

  10、 确定原子立构中心数量：0

  11、 不确定原子立构中心数量：0

  12、 确定化学键立构中心数量：0

  13、 不确定化学键立构中心数量：0

  14、 共价键单元数量：1

• 更多:

  1. 性状：微白色粉末。

  2. 密度（g/mL,25/4℃）：未确定

  3. 相对蒸汽密度（g/mL,空气=1）：未确定

  4. 熔点（ºC）：230-235

  5. 沸点（ºC,常压）：未确定

  6. 沸点（ºC,5.2kPa）：未确定

  7. 折射率：未确定

  8. 闪点（ºC）：未确定

  9. 比旋光度（º）：未确定

  10. 自燃点或引燃温度（ºC）：未确定

  11. 蒸气压（kPa,25ºC）：未确定

  12. 饱和蒸气压（kPa,60ºC）：未确定

  13. 燃烧热（KJ/mol）：未确定

  14. 临界温度（ºC）：未确定

  15. 临界压力（KPa）：未确定

  16. 油水（辛醇/水）分配系数的对数值：未确定

  17. 爆炸上限（%,V/V）：未确定

  18. 爆炸下限（%,V/V）：未确定

  19. 溶解性：溶于水，易溶于乙醇，几乎不溶于氯仿。

生物活性

• 描述: Alendronic acid,一种双膦酸盐,是法呢基二磷酸合酶 (FDPS) 抑制剂。Alendronic acid 抑制破骨细胞介导的骨吸收。Alendronic acid 对绝经后骨质疏松症,恶性高钙血症和 Paget 病具有疗效。
• 相关类别:
  研究领域 >> 癌症
  信号通路 >> 其他 >> 其他
• 体外研究: 双膦酸盐广泛应用于骨质疏松症的治疗,其中阿仑膦酸是最常用的处方药。双膦酸盐对骨重塑有强大的抑制作用,这一过程对骨折愈合至关重要【2】。
• 参考文献:

  [1]. Teixeira S, et al. Alendronic Acid as Ionic Liquid: New Perspective on Osteosarcoma. Pharmaceutics. 2020 Mar 24;12(3). pii: E293.

  [2]. Duckworth AD, et al. Effect of Alendronic Acid on Fracture Healing: A Multicenter Randomized Placebo-Controlled Trial. J Bone Miner Res. 2019 Jun;34(6):1025-1032.

MSDS

Section I.Chemical Product and Company Identification Chemical Name Alendronic Acid Portland OR SynonymPhosphonic acid, P,P'-(4-amino-1- hydroxybutylidene)bis- (CA INDEX NAME); 4-Amino-1-hydroxybutane-1,1-diphosphonic Acid Chemical FormulaC4H13NO7P2 CAS Number66376-36-1 Section II.Composition and Information on Ingredients Toxicology Data Chemical NameCAS Number Percent (%)TLV/PEL 66376-36-1 Min. 98.0 (T) Not available.Not available. Alendronic Acid Section III. Hazards Identification Acute Health EffectsCorrosive to skin, eyes, and respiratory system. Liquid or spray mist may produce tissue damage, particularly in mucous membranes of the eyes, mouth and respiratory tract. Skin contact may produce burns. Eye contact can result in corneal damage or blindness. Inhalation of the spray mist may produce severe irritation of respiratory tract, characterized by coughing, choking, or shortness of breath. Corrosive materials may cause serious injury if ingested. Follow safe industrial hygiene practices and always wear proper protective equipment when handling this compound. Chronic Health EffectsCARCINOGENIC EFFECTS : Not available. MUTAGENIC EFFECTS : Not available. TERATOGENIC EFFECTS : Not available. DEVELOPMENTAL TOXICITY: Reproductive Effects. Rat TDLo Subcutaneous 2 mg/kg, female 11-20 days of pregnancy TOXIC Effects: Specific Developmental Abnormalities - Musculoskeletal system Repeated exposure of the eyes to a low level of dust can produce eye irritation. Repeated skin exposure can produce local skin destruction, or dermatitis. Repeated inhalation of dust can produce varying degree of respiratory irritation or lung damage. Section IV.First Aid Measures Eye Contact Check for and remove any contact lenses. In case of contact, immediately flush eyes with plenty of water for at least 15 minutes. Get medical attention. Skin ContactIn case of contact, immediately flush skin with plenty of water. Remove contaminated clothing and shoes. Wash clothing before reuse. Thoroughly clean shoes before reuse. Get medical attention. InhalationIf the victim is not breathing, perform mouth-to-mouth resuscitation. Loosen tight clothing such as a collar, tie, belt or waistband. If breathing is difficult, oxygen can be administered. Seek medical attention if respiration problems do not improve. IngestionDO NOT INDUCE VOMITING. Loosen tight clothing such as a collar, tie, belt or waistband. If the victim is not breathing, perform mouth-to-mouth resuscitation. Examine the lips and mouth to ascertain whether the tissues are damaged, a possible indication that the toxic material was ingested; the absence of such signs, however, is not conclusive. Section V.Fire and Explosion Data Not available. Auto-Ignition FlammabilityMay be combustible at high temperature. Flammable Limits Flash PointsNot available. Not available. Combustion ProductsThese products are toxic carbon oxides (CO, CO 2), nitrogen oxides (NO, NO2), phosphates. Fire Hazards Not available. Explosion HazardsRisks of explosion of the product in presence of mechanical impact: Not available. Risks of explosion of the product in presence of static discharge: Not available. Continued on Next Page Alendronic Acid Fire Fighting Media SMALL FIRE: Use DRY chemical powder. and InstructionsLARGE FIRE: Use water spray, fog or foam. DO NOT use water jet. Consult with local fire authorities before attempting large scale fire-fighting operations. Section VI.Accidental Release Measures Spill Cleanup Corrosive material. Stop leak if without risk. DO NOT get water inside container. DO NOT touch spilled material. Use water spray to reduce Instructions vapors. Prevent entry into sewers, basements or confined areas; dike if needed. Eliminate all sources of ignition. Consult federal, state, and/or local authorities for assistance on disposal. Section VII. Handling and Storage CORROSIVE. Keep container dry. Keep away from heat. Mechanical exhaust required. When not in use, tightly seal the Handling and Storage container and store in a dry, cool place. Avoid excessive heat and light. Do not breathe dust. Never add water to this Information product. Wear suitable protective clothing. If you feel unwell, seek medical attention and show the label when possible. Treat symptomatically and supportively. Always store away from incompatible compounds such as oxidizing agents. Section VIII. Exposure Controls/Personal Protection Engineering ControlsUse process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below recommended exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to airborne contaminants below the exposure limit. Personal ProtectionFace shield. Lab coat. Dust respirator. Boots. Gloves. A MSHA/NIOSH approved respirator must be used to avoid inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist BEFORE handling this product. Exposure LimitsNot available. Section IX. Physical and Chemical Properties Physical state @ 20°CSolid. (White ~ light yellow, crystal.)Solubility Not available. Not available. Specific Gravity Molecular Weight249.1Partition Coefficient Not available. Boiling PointVapor Pressure Not available.Not applicable. Not available.Not available. Melting PointVapor Density Refractive IndexNot available.VolatilityNot available. Critical TemperatureNot available.OdorNot available. ViscosityNot available.TasteNot available. Section X.Stability and Reactivity Data Stability This material is stable if stored under proper conditions. (See Section VII for instructions) Conditions of Instability Avoid excessive heat and light. Incompatibilities Reactive with oxidizing agents. Section XI. Toxicological Information RTECS NumberSZ6521833 Routes of ExposureEye Contact. Ingestion. Inhalation. Toxicity DataNot available. CARCINOGENIC EFFECTS : Not available. Chronic Toxic Effects MUTAGENIC EFFECTS : Not available. TERATOGENIC EFFECTS : Not available. DEVELOPMENTAL TOXICITY: Reproductive Effects. Rat TDLo Subcutaneous 2 mg/kg, female 11-20 days of pregnancy TOXIC Effects: Specific Developmental Abnormalities - Musculoskeletal system Repeated exposure of the eyes to a low level of dust can produce eye irritation. Repeated skin exposure can produce local skin destruction, or dermatitis. Repeated inhalation of dust can produce varying degree of respiratory irritation or lung damage. Continued on Next Page Alendronic Acid Acute Toxic EffectsCorrosive to skin, eyes, and respiratory system. Liquid or spray mist may produce tissue damage, particularly in mucous membranes of the eyes, mouth and respiratory tract. Skin contact may produce burns. Eye contact can result in corneal damage or blindness. Inhalation of the spray mist may produce severe irritation of respiratory tract, characterized by coughing, choking, or shortness of breath. Corrosive materials may cause serious injury if ingested. Follow safe industrial hygiene practices and always wear proper protective equipment when handling this compound. Section XII.Ecological Information EcotoxicityNot available. Environmental FateNot available. Section XIII. Disposal Considerations Recycle to process, if possible. Consult your local regional authorities. You may be able to dissolve or mix material with a Waste Disposal combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber system. Observe all federal, state and local regulations when disposing of the substance. Section XIV. Transport Information DOT Classification DOT Class 8: Corrosive material PIN Number Proper Shipping Name Corrosive solid, n.o.s. Packing Group (PG)III DOT Pictograms Section XV. Other Regulatory Information and Pictograms TSCA Chemical InventoryThis product is NOT on the EPA Toxic Substances Control Act (TSCA) inventory. The following notices are required by 40 CFR 720.36 (C) for those products not on the inventory list: (EPA) (i) These products are supplied solely for use in research and development by or under the supervision of a technically qualified individual as defined in 40 CFR 720.0 et sec. (ii) The health risks of these products have not been fully determined. Any information that is or becomes available will be supplied on an MSDS sheet. WHMIS Classification CLASS E: Corrosive solid. (Canada) EINECS Number (EEC) Not available. EEC Risk Statements R34- Causes burns. SECTION 16 - ADDITIONAL INFORMATION N/A

毒性和生态

生态学数据: 通常对水是不危害的，若无政府许可，勿将材料排入周围环境。

安全

• 危险品运输编码: 1759
• RTECS号: SZ6521833
• 包装等级: III
• 海关编码: 2931900090

合成路线

56-12-2 ~92% 66376-36-1

文献：ORCHID CHEMICALS and PHARMACEUTICALS LTD. Patent: US2007/66569 A1, 2007 ; Location in patent: Page/Page column 2 ;

948317-79-1 ~83% 66376-36-1

文献：Guenin, Erwann; Monteil, Maelle; Bouchemal, Nadia; Prange, Thierry; Lecouvey, Marc European Journal of Organic Chemistry, 2007 , # 20 p. 3380 - 3391

69038-04-6 ~59% 66376-36-1

文献：Guenin, Erwann; Monteil, Maelle; Bouchemal, Nadia; Prange, Thierry; Lecouvey, Marc European Journal of Organic Chemistry, 2007 , # 20 p. 3380 - 3391

121268-17-5 ~% 66376-36-1

文献：WO2005/47282 A1, ; Page/Page column 8 ;

616-45-5 ~70% 66376-36-1

文献：Xu, Guangyu; Xie, Yuyuan; Wu, Xihan Organic Preparations and Procedures International, 2004 , vol. 36, # 2 p. 185 - 187

125040-13-3 ~% 66376-36-1

文献：Phosphorus, Sulfur and Silicon and the Related Elements, , vol. 63, # 1/2 p. 181 - 192

10314-06-4 ~% 66376-36-1

文献：Phosphorus, Sulfur and Silicon and Related Elements, , vol. 129, p. 99 - 110

上下游产品

上游产品  6
56-12-2 69038-04-6 121268-17-5 616-45-5
125040-13-3 10314-06-4
下游产品  1
121268-17-5

制备

1.将1mol 4-氨基丁酸加入95℃的熔融的1.5mol磷酸，然后在60min中滴加2mol三卤化磷。当反应物硬化后，再加热3h。加入300ml水进行水解，冷却后倾入1500ml甲醇，收集沉淀，得到64.6%的阿仑膦酸。

2.在4-氨基丁酸与磷酸中，滴加三卤化磷反应。当反应物硬化后，再加热，加入水进行水解，冷却后放入甲醇，收集即得阿仑膦酸。

海关

海关编码	2931900090
中文概述	2931900090. 其他有机-无机化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:AB(入境货物通关单,出境货物通关单). 最惠国关税:6.5%. 普通关税:30.0%
Summary	2931900090. other organo-inorganic compounds. VAT:17.0%. Tax rebate rate:13.0%. Supervision conditions:AB(certificate of inspection for goods inward,certificate of inspection for goods outward). MFN tariff:6.5%. General tariff:30.0%