阿仑膦酸 | 66376-36-1

• 物质功能分类: 原料药 - 水、电解质及酸碱平衡调节药 - 电解质平衡调节药
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 中文名称: 阿仑膦酸
• 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；阿仑唑奈
• 英文名称: 4-amino-1-hydroxybutylidenebisphosphonic acid
• 英文别名: ALENDRONATE；alendronic acid；alendronate sodium；(4-Azaniumyl-1-hydroxy-1-phosphonobutyl)-hydroxyphosphinate
• CAS: 66376-36-1
• 化学式: C₄H₁₃NO₇P₂
• mdl: MFCD00868112
• 分子量: 249.097
• InChiKey: OGSPWJRAVKPPFI-UHFFFAOYSA-N

物化性质

• 熔点：
  230-235°C
• 沸点：
  616.7±65.0 °C(Predicted)
• 密度：
  1.857±0.06 g/cm3(Predicted)
• 溶解度：
  水基（少量溶解）、甲醇（少量溶解）、水（非常少量）
• 物理描述：
  Solid
• 颜色/状态：
  Fine white powder
• 蒸汽压力：
  4.90X10-13 mm Hg at 25 °C (est)
• 解离常数：
  pKa1 = 2.72; pKa2 = 8.73; pKa3 = 10.5; pKa4 = 11.6 (all at 25 °C)
• 稳定性/保质期：
  在常温常压下保持稳定，请远离氧化剂。

计算性质

• 辛醇/水分配系数(LogP)：
  -6.5
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  161
• 氢给体数：
  6
• 氢受体数：
  8

ADMET

代谢

尿排泄是消除阿仑膦酸的唯一方法，收集尿液时未检测到代谢物。

Urinary excretion is the sole method of elimination of alendronic acid and no metabolites are detected upon urine collection.

来源:DrugBank

代谢

没有证据表明阿仑膦酸在动物或人类中会被代谢。

There is no evidence that alendronate is metabolized in animals or humans.

来源:Hazardous Substances Data Bank (HSDB)

代谢

没有证据表明阿仑膦酸在人体或动物中会被代谢。 消除途径：在单次静脉注射[14C]阿仑膦酸后，大约50%的放射性物质在72小时内通过尿液排出，而在粪便中几乎没有或没有检测到放射性物质。 半衰期：>10年

There is no evidence that alendronate is metabolized in humans or animals. Route of Elimination: Following a single IV dose of [14C]alendronate, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no radioactivity was recovered in the feces. Half Life: >10 years

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

阿仑膦酸对骨组织的作用部分基于其对羟基磷灰石的亲和力，羟基磷灰石是骨矿基质的一部分。阿仑膦酸还针对法尼基焦磷酸酯（FPP）合酶。含氮双膦酸盐（如帕米膦酸、阿仑膦酸、利塞膦酸、伊班膦酸和唑来膦酸）似乎作为异戊二烯二磷酸脂质的类似物发挥作用，从而抑制FPP合酶，该酶是美伐仑酸途径中的酶。在破骨细胞中抑制这种酶可以阻止异戊二烯脂质（FPP和GGPP）的生物合成，这些脂质对于小GTPase信号蛋白的翻译后法尼基化和香叶基化是必不可少的。这种活性抑制破骨细胞活动并减少骨吸收和转换。在绝经后妇女中，它降低了骨转换的升高速率，平均而言，导致骨质量的净增加。

The action of Alendronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Alendronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 药物性肝损伤

化合物：阿仑膦酸酯

Compound:alendronate

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

药物性肝损伤标注：低药物性肝损伤关注

DILI Annotation:Less-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

标签部分：无匹配

Label Section:No match

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 美国食品药品监督管理局批准的药物标签用于研究药物诱导的肝损伤，《药物发现今日》，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按人类发展药物诱导肝损伤风险排名的最大参考药物清单。《药物发现今日》2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

阿仑膦酸在女性中的平均口服生物利用度为0.64%，在男性中为0.59%。如果阿仑膦酸在饭后一小时内服用，其生物利用度会降低多达40%。

Mean oral bioavailability of alendronic acid in women is 0.64% and in men is 0.59%. Bioavailability of alendronic acid decreases by up to 40% if it is taken within an hour of a meal.

来源:DrugBank

吸收、分配和排泄

• 消除途径

单剂量服用放射性标记的阿仑膦酸治疗后，72小时内尿液中可回收约50%。粪便中未检测到阿仑膦酸。男性排泄的阿仑膦酸少于女性，但种族和年龄不影响消除。

Administration of radiolabeled alendronic acid results in 50% recovery in urine within 72 hours. No alendronic acid is recovered in the feces. Men excrete less alendronic acid than women, though race and advanced age do not affect elimination.

来源:DrugBank

吸收、分配和排泄

• 分布容积

28升。

28L.

来源:DrugBank

吸收、分配和排泄

• 清除

71毫升/分钟。

71mL/min.

来源:DrugBank

吸收、分配和排泄

相对于静脉注射参考剂量，女性在隔夜禁食后并在标准化早餐前两小时服用阿仑膦酸钠，剂量从5毫克到70毫克时，平均口服生物利用度为0.64%。男性服用10毫克片剂的口服生物利用度（0.59%）与女性在隔夜禁食后并在早餐前两小时服用时的生物利用度相似。

Relative to an intravenous iv reference dose, the mean oral bioavailability of alendronate in women was 0.64% for doses ranging from 5 to 70 mg when administered after an overnight fast and two hours before a standardized breakfast. Oral bioavailability of the 10 mg tablet in men (0.59%) was similar to that in women when administered after an overnight fast and 2 hours before breakfast.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  8
• RTECS号：
  SZ6521833
• 海关编码：
  2931900090
• 包装等级：
  II
• 危险类别：
  8
• 危险性防范说明：
  P280,P305+P351+P338,P310
• 危险品运输编号：
  1759
• 危险性描述：
  H314
• 储存条件：
  存放在密封容器内，并置于阴凉、干燥处。请确保储存位置远离氧化剂。

SDS

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Section I.Chemical Product and Company Identification
Chemical Name Alendronic Acid
Portland OR
Synonym Phosphonic acid, P,P'-(4-amino-1-
hydroxybutylidene)bis- (CA INDEX NAME);
4-Amino-1-hydroxybutane-1,1-diphosphonic Acid
Chemical Formula C4H13NO7P2
CAS Number 66376-36-1

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Section II. Composition and Information on Ingredients
Toxicology Data
Chemical Name CAS Number Percent (%) TLV/PEL
66376-36-1 Min. 98.0 (T) Not available. Not available.
Alendronic Acid

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Section III. Hazards Identification
Acute Health Effects Corrosive 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 Effects CARCINOGENIC 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.

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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 Contact In 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.
Inhalation If 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.
Ingestion DO 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.

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Section V. Fire and Explosion Data
Not available.
Auto-Ignition
Flammability May be combustible at high temperature.
Flammable Limits
Flash Points Not available.
Not available.
Combustion Products These products are toxic carbon oxides (CO, CO 2), nitrogen oxides (NO, NO2), phosphates.
Fire Hazards
Not available.
Explosion Hazards Risks 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 Instructions LARGE FIRE: Use water spray, fog or foam. DO NOT use water jet.
Consult with local fire authorities before attempting large scale fire-fighting operations.

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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.

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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.

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Section VIII. Exposure Controls/Personal Protection
Engineering Controls Use 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 Protection Face 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 Limits Not available.

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Section IX. Physical and Chemical Properties
Physical state @ 20°C Solid. (White ~ light yellow, crystal.) Solubility
Not available.
Not available.
Specific Gravity
Molecular Weight 249.1 Partition Coefficient
Not available.
Boiling Point Vapor Pressure
Not available. Not applicable.
Not available. Not available.
Melting Point Vapor Density
Refractive Index Not available. Volatility Not available.
Critical Temperature Not available. Odor Not available.
Viscosity Not available. Taste Not available.

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Section X. Stability and Reactivity Data
Stability

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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.

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Section XI. Toxicological Information
RTECS Number SZ6521833
Routes of Exposure Eye Contact. Ingestion. Inhalation.
Toxicity Data Not 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 Effects Corrosive 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.

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Section XII. Ecological Information
Ecotoxicity Not available.
Environmental Fate Not available.

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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.

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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

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Section XV. Other Regulatory Information and Pictograms
TSCA Chemical Inventory This 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.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

Alendronic acid 是一种双膦酸盐，属于法呢基二磷酸合酶 (FDPS) 抑制剂。它能抑制破骨细胞介导的骨吸收，并对绝经后骨质疏松症、恶性高钙血症和 Paget 病具有疗效。

体外研究

双膦酸盐在治疗骨质疏松症中广泛使用，其中阿仑膦酸是最常开具的药物之一。这些药物能够强有力地抑制骨重塑过程，这一过程对于骨折愈合至关重要。

化学性质

Alendronic acid 是一种细微白色粉末，熔点为233～235℃（分解）。其pKa值分别为：2.72±0.05；8.73±0.05；10.5±0.1；11.6±0.1（在2512，0.1mol/L氯化钾中）。

用途

阿仑膦酸是一种二膦酸类骨吸收抑制剂，用于治疗骨质疏松症。

生产方法

将1摩尔4-氨基丁酸加入95℃熔融的1.5摩尔磷酸中，然后在60分钟内滴加2摩尔三卤化磷。当反应物硬化后，再加热3小时。随后，加入300毫升水进行水解，并冷却后倾入1500毫升甲醇中，收集沉淀以得到64.6%的阿仑膦酸。

反应信息

• 作为反应物：
  描述：

  阿仑膦酸 在 sodium carbonate 作用下， 以 水 为溶剂， 反应 3.0h， 以79%的产率得到sodium alendronate
  参考文献：
  名称：

  阿仑膦酸钠碱金属盐中超分子相互作用分析：新型阿仑膦酸钠多晶型物的合成、结构和性质

  摘要：

  合成了一种新的无水阿仑膦酸钠多晶型物 C4H12NO7P2Na，并通过单晶 X 射线衍射、红外光谱和热分析对其进行了表征。标题化合物在单斜 P21/c 空间群中结晶。不对称单元由一个阿仑膦酸阴离子和一个钠阳离子组成。经典强 OH…O、NH…O 和非经典弱 CH…O 氢键的相互作用在晶体中创建 3D 框架。与之前报道的阿仑膦酸钠盐相反，其中 Na+ 阳离子被六配位球包围，在化合物 (1) 中，Na+ 阳离子在扭曲的三角双锥几何中是五配位的。为了根据分子间相互作用对分子排列进行详细研究，将标题化合物与阿仑膦酸和其他已知的碱金属阿仑膦酸盐（从剑桥晶体结构数据库检索）进行比较。使用 Hirshfeld 表面分析对相互接触进行定性和定量比较。它强调了强 O…H/H…O 和微妙的 H…H 接触在总表面积中起着重要作用。Me+...H/H...Me+ 和 Me+...O/O...Me+ 触点也很有意义。

  DOI：

  10.1007/s11224-018-1140-2
• 作为产物：
  描述：

  sodium alendronate 在 盐酸 、 乙醇 、 水 作用下， 反应 2.0h， 生成 阿仑膦酸
  参考文献：
  名称：

  [EN] ANTIRESORPTIVE MUTUAL SALT OF RALOXIFENE AND BISPHOSPHONIC ACID
  [FR] SELS ANTIRESORBANTS DE RALOXIFENE ET D'ACIDE BIPHOSPHONIQUE

  摘要：

  来自拉洛西芬和双磷酸盐的相互盐表现出两种成分之间意想不到的协同效应，以增强骨密度（BMD）、控制血钙密度并降低血清胆固醇水平。

  公开号：

  WO2005047282A1

文献信息

• Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis
  作者：Salvatore Savino、Annamaria Toscano、Rosa Purgatorio、Emanuela Profilo、Antonio Laghezza、Paolo Tortorella、Mariacristina Angelelli、Saverio Cellamare、Rosa Scala、Domenico Tricarico、Carlo Marya Thomas Marobbio、Filippo Perna、Paola Vitale、Mariangela Agamennone、Vincenzo Dimiccoli、Anna Tolomeo、Antonio Scilimati

  DOI：10.1016/j.ejmech.2018.08.044

  日期：2018.10

  ethane-1,1-diyl]bis(phosphonic acid) (10) was effective in reducing PC3 and RAW 264.7 cell number in crystal-violet and cell-dehydrogenase activity assays at 100 μM concentration. 10 reduced differentiated osteoclasts number similarly with zoledronic acid in osteoclastogenesis assay. At nanomolar concentrations, 10 was more effective than zoledronic acid in inducing mineralization in MC3T3 and murine

  双膦酸盐，例如唑来膦酸，阿仑膦酸和利塞膦酸是临床上用于预防骨密度损失和骨质疏松症的一类药物。合成了新的PCP双膦酸酯，用于靶向人甲羟戊酸途径的关键酶人法呢基焦磷酸合酶（h FPPS）和人香叶基Geranylgeranyl焦磷酸合酶（h GGPPS），并且能够在多种细胞系（PC3，MG63， MC3T3，RAW 264.7，J774A.1，骨髓细胞及其与PC3的共配基涉及骨骼的体内稳态，骨骼形成和死亡。在16种化合物中，[1-羟基-2-（嘧啶-2-基氨基）乙烷-1,1-二基]双（膦酸）（10）在100μM浓度的结晶紫和细胞脱氢酶活性测定中可有效减少PC3和RAW 264.7细胞数量。在破骨细胞生成测定中，与唑来膦酸相似地减少了10个分化的破骨细胞数量。在纳摩尔浓度下，10在诱导MC3T3和鼠骨髓细胞中的矿化作用上比唑来膦酸更有效。此外，10显着抑制h FPPS的活性，IC 50为0.31μM
• Syntheses of Phosphonic Esters of Alendronate, Pamidronate and Neridronate
  作者：Erwann Guénin、Maelle Monteil、Nadia Bouchemal、Thierry Prangé、Marc Lecouvey

  DOI：10.1002/ejoc.200601067

  日期：2007.7

  Several synthetic pathways for obtaining phosphonic esters of the amino bisphosphonic acids (NBPs) pamidronate, alendronate and neridronate were investigated. The general guideline was to react N-protected amino acids activated as phthalimide esters or as acyl chlorides. Succinimide esters were found less reactive and quickly abandoned. gamma-Lactam formation arises when starting from Boc- or Cbz-protected

  研究了获得氨基双膦酸 (NBPs) pamidronate、alendronate 和 neridronate 膦酸酯的几种合成途径。一般指导原则是将 N 保护的氨基酸作为邻苯二甲酰亚胺酯或酰氯活化。发现琥珀酰亚胺酯的反应性较低并很快被废弃。当从 Boc 或 Cbz 保护的氨基酸开始时，会形成 γ-内酰胺。邻苯二甲酰亚胺 N-保护基团允许以高产率获得这三种 NBP 的烷基或芳基单酯、二酯（对称或非对称）和三酯。((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)。
• 신규 mTOR 억제제 화합물 및 이의 용도
  申请人：Ewha University - Industry Collaboration Foundation 이화여자대학교 산학협력단(220040083301) BRN ▼110-82-10456

  公开号：KR20210023576A

  公开（公告）日：2021-03-04

  본 발명의 신규 mTOR 억제제 화합물은 뼈에 대하여 선택적으로 약물 전달이 가능하며 뼈에서 오랜 기간 서서히 방출될 수 있도록, 골 지향성 리간드를 mTOR 억제 뼈 질환 치료제에 연결한 표적지향성 화합물에 관한 것이다.

  这项新型 mTOR 抑制剂化合物能够选择性地在骨骼中进行药物传递，并且能够在骨骼中缓慢释放长时间，这是关于将骨向性配体连接到 mTOR 抑制剂骨疾病治疗剂的靶向化合物的。
• Non-hydrolysable analogues of inorganic pyrophosphate as inhibitors of hepatitis C virus RNA-dependent RNA-polymerase
  作者：D. V. Yanvarev、A. N. Korovina、N. N. Usanov、S. N. Kochetkov

  DOI：10.1134/s1068162012020124

  日期：2012.3

  Inorganic pyrophosphate (PPi) is the product of the polymerization reaction catalyzed by DNA- and RNA-polymerases. A number of novel non-hydrolsable PPi analogues was synthesized; some of them inhibited the polymerization reaction catalyzed by hepatitis C virus RNA-dependent RNA-polymerase (NS5B). A new pharmacophore based on a non-hydrolysable methylenediphosphonate backbone has been developed. The

  无机焦磷酸盐 (PPi) 是由 DNA 和 RNA 聚合酶催化的聚合反应产物。合成了许多新型的不可水解的 PPi 类似物；其中一些抑制了丙型肝炎病毒 RNA 依赖性 RNA 聚合酶 (NS5B) 催化的聚合反应。已开发出基于不可水解的亚甲基二膦酸酯骨架的新药效团。介绍了 12 种双膦酸盐的构效关系分析，并说明了对 NS5B 聚合酶活性抑制至关重要的结构特征。
• Phospholipid compounds and formulations
  申请人：Applaud Medical, Inc.

  公开号：US10953023B1

  公开（公告）日：2021-03-23

  The present disclosure provides phospholipid-containing compounds, pharmaceutical compositions and microspheres that exhibit high affinity for mineralized metals. The present disclosure also provides strategies for using said compounds, compositions and microspheres in the treatment of nephrolithiasis or kidney stone disease, and methods of manufacturing and preparing said compounds and compositions.

  本公开提供含磷脂化合物、制药组合物和微球，这些化合物、组合物和微球具有高亲和力对矿化金属。本公开还提供使用这些化合物、组合物和微球治疗肾结石病或肾结石疾病的策略，以及制备这些化合物和组合物的方法。

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