甲状腺素 | 51-48-9

• 物质功能分类: 原料药 - 激素及调节内分泌功能类药 - 甲状腺激素及抗甲状腺药
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 甲状腺素
• 中文别名: L-甲状腺素；O-(4-羟基-3,5-二碘苯基)-3,5-二碘-L-酪氨酸；L-甲状腺激素；甲四碘胺；甲状腺素左旋甲状腺素；2-甲状腺素；甲四碘安,LEVOTHYROXINE；3,5,3',5'-四碘甲状腺胺酸；左旋甲状腺素；D-ALPHA-生育酚；D-Α-生育酚；3,3',5,5''-四碘代-L-甲状腺原氨酸；L-Β-(3,5-二磺-4-羟基苯氧基)-3,5-二磺苯丙氨酸；左甲状腺素
• 英文名称: L-thyroxine
• 英文别名: Levothyroxine；L-Thyroxin；thyroxine；(2S)-2-ammonio-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoate；(2S)-2-azaniumyl-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoate
• CAS: 51-48-9
• 化学式: C₁₅H₁₁I₄NO₄
• mdl: MFCD00063058
• 分子量: 776.875
• InChiKey: XUIIKFGFIJCVMT-LBPRGKRZSA-N

物化性质

• 熔点：
  235 °C
• 比旋光度：
  -5 º (1N NaOH:EtOH 1:2)
• 密度：
  2.4440 (estimate)
• 闪点：
  9℃
• 溶解度：
  以50mg/ml溶于4M氢氧化铵的甲醇溶液
• 沸点：
  576.3±50.0 °C(Predicted)
• 物理描述：
  Solid
• 颜色/状态：
  Crystals
• 蒸汽压力：
  2.05X10-16 mm Hg at 25 °C (est)
• 稳定性/保质期：

  在常温常压下保持稳定，请避免光照、明火及高温环境。

• 旋光度：
  Specific optical rotation: -4.4 deg at 20 °C/D (3% in 0.13N sodium hydroxide in 70% ethanol)
• 分解：
  When heated to decomposition it emits toxic fumes.
• 解离常数：
  pKa1 = 0.27 (carboxylic); pKa2 = 7.43 (phenol); pKa3 = 9.43 (amine) (est)
• 碰撞截面：
  216.2 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  92.8
• 氢给体数：
  3
• 氢受体数：
  5

ADMET

代谢

大约70%的分泌的T4通过脱碘作用转化为等量的T3和反向三碘甲状腺原氨酸（rT3），后者在产热方面是无效的。T4通过其主要代谢途径逐渐转化为T3，通过连续脱碘作用，其中大约80%的循环T3来自外周T4。肝脏是T4和T3降解的主要场所，T4的脱碘作用也发生在包括肾脏和其他组织在内的多个额外场所。T4和T3的消除涉及肝脏与葡萄糖醛酸和硫酸的共轭作用。这些激素作为共轭物在肠道中被水解并重新吸收，从而经历肠肝循环。到达结肠的共轭化合物被水解并以自由化合物的形式随粪便排出。还鉴定出了其他一些T4的次要代谢物。

Approximately 70% of secreted T₄ is deiodinated to equal amounts of T₃ and reverse triiodothyronine (rT₃), which is calorigenically inactive. T₄ is slowly eliminated through its major metabolic pathway to T₃ via sequential deiodination, where approximately 80% of circulating T₃ is derived from peripheral T₄. The liver is the major site of degradation for both T₄ and T₃, with T₄ deiodination also occurring at a number of additional sites, including the kidney and other tissues. Elimination of T₄ and T₃ involves hepatic conjugation to glucuronic and sulfuric acids. The hormones undergo enterohepatic circulation as conjugates are hydrolyzed in the intestine and reabsorbed. Conjugated compounds that reach the colon are hydrolyzed and eliminated as free compounds in the feces. Other minor T₄ metabolites have been identified.

来源:DrugBank

代谢

在兔中产生L-酪氨酸，在大鼠中产生/从表中/。

Yields l-tyrosine in rabbit, in rat /From table/

来源:Hazardous Substances Data Bank (HSDB)

代谢

在人、大鼠、狗、兔中产生3,3',5-三碘-L-甲状腺素。/根据表格/

Yields 3,3',5-triiodo-L-thyronine in man, rat, dog, rabbit. /From table/

来源:Hazardous Substances Data Bank (HSDB)

代谢

在狗、人和大鼠中产生L-甲状腺素-4'-β-D-葡萄糖苷酸。在狗中产生L-甲状腺素-4'-硫酸盐。/根据表格/

Yields l-thyroxine-4'-beta-d-glucuronide in dog, in man, in rat. Yields l-thyroxine-4'-sulfate in dog. /From table/

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠中产生3,3',5,5'-四碘甲状腺原酸。在大鼠中产生L-甲状腺素。/根据表格/

Yields 3,3',5,5'-tetraiodothyropyruvic acid in rat. Yields l-thyronine in rat. /From table/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：左甲状腺素以晶体或针状形式存在。作为一种药物，左甲状腺素钠用于治疗先天或后天性甲状腺功能减退的替代或补充疗法。它还用于治疗或预防各种类型的甲状腺功能正常的甲状腺肿，包括甲状腺结节、亚急性或慢性淋巴细胞性甲状腺炎（桥本甲状腺炎）、多结节性甲状腺肿，以及在治疗促甲状腺激素依赖性分化良好的甲状腺癌中作为手术和放射性碘治疗的辅助。左甲状腺素钠的注射剂型用于治疗黏液性昏迷。左甲状腺素还曾在兽医医学中使用。人类暴露和毒性：左甲状腺素过量的症状和体征是甲状腺功能亢进的表现。此外，可能出现混乱和定向障碍。已报告有脑栓塞、休克、昏迷和死亡的情况。研究表明，在极低出生体重婴儿开始给予左甲状腺素钠时需要特别注意。儿童摄入左甲状腺素通常病程良性，但过量可能导致严重并发症，包括癫痫和心律失常，这两种情况都应予以监测。在一项遗传毒性研究中，测试了甲状腺素在培养的人淋巴细胞中诱导姐妹染色单体交换和微核的能力。甲状腺素仅在较高浓度下表现出微弱的断裂作用。动物研究：单一急性过量在小动物中不太可能导致严重的甲状腺功能亢进，而慢性过量则可能。在狗和猫中可能会观察到呕吐、腹泻、从过度活跃到嗜睡的转变、高血压、心动过速、呼吸过速、呼吸困难以及异常的瞳孔光反射。在狗中，临床体征可能在摄入后1-9小时内出现。四只新西兰白兔在妊娠的第25和26天通过肌内注射给予250微克/千克的左甲状腺素。母体和胎儿血浆中游离左甲状腺素浓度高于对照组，在新生期的第14天观察到最高浓度。治疗导致胎儿高血糖和胎儿肝脏糖原含量的减少。尚未进行动物研究以评估左甲状腺素的致癌潜力、致突变潜力或对生育能力的影响。

IDENTIFICATION AND USE: Levothyroxine occurs as crystals or needles. As a drug, levothyroxine sodium is used as replacement or supplemental therapy in congenital or acquired hypothyroidism. It is also used in the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto's thyroiditis), multinodular goiter and, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer. The injection form of levothyroxine sodium is indicated for the treatment of myxedema coma. Levothyroxine has also been used in veterinary medicine. HUMAN EXPOSURE AND TOXICITY: The signs and symptoms of levothyroxine overdosage are those of hyperthyroidism. In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. Studies indicate that careful attention is necessary when initiating the administration of levothyroxine sodium to very-low-birth-weight infants. Ingestion of levothyroxine in children typically follows a benign course, but overdose can result in significant complications, including seizures and arrhythmias, both of which should be monitored for. In one genotoxicity study, the ability of thyroxine to induce sister chromatid exchange and micronuclei was tested in cultured human lymphocytes. Thyroxine exhibited weak clastogenic effects only at high concentrations. ANIMAL STUDIES: A single acute overdose in small animals is less likely to cause severe thyrotoxicosis than chronic overdosage. Vomiting, diarrhea, transition from hyperactivity to lethargy, hypertension, tachycardia, tachypnea, dyspnea, and abnormal pupillary light reflexes may be noted in dogs and cats. In dogs, clinical signs may appear within 1-9 hours after ingestion. Four pregnant New Zealand white rabbits received intramuscular levothyroxine at 250 ug/kg on days 25 and 26 of gestation. Maternal and fetal plasma-free levothyroxine concentration was higher than in controls, with the highest concentration noted at 14 days of neonatal period. Treatment resulted in fetal hyperglycemia and depletion of fetal liver glycogen content. Animal studies have not been performed to evaluate levothyroxine carcinogenic potential, mutagenic potential or effects on fertility.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 药物性肝损伤

左甲状腺素

Compound:levothyroxine

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

严重程度等级：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

口服给药的T4从胃肠道的吸收率在40%到80%之间，其中大部分左甲状腺素剂量从空肠和近端回肠吸收。T4的吸收在空腹时增加，在吸收不良综合症和某些食物如大豆、牛奶和膳食纤维存在时减少。吸收也可能随着年龄的增长而减少。此外，许多药物影响T4的吸收，包括胆酸螯合剂、硫糖铝、质子泵抑制剂以及钙（包括酸奶和乳制品）、镁、铁和铝的补充剂。为了防止形成不溶性螯合物，左甲状腺素通常应在空腹时服用，至少在饭前2小时，并与任何相互作用剂至少间隔4小时。

Absorption of orally administered T4 from the gastrointestinal tract ranges from 40% to 80% with the majority of the levothyroxine dose absorbed from the jejunum and upper ileum. T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybeans, milk, and dietary fiber. Absorption may also decrease with age. In addition, many drugs affect T4 absorption including bile acide sequestrants, sucralfate, proton pump inhibitors, and minerals such as calcium (including in yogurt and milk products), magnesium, iron, and aluminum supplements. To prevent the formation of insoluble chelates, levothyroxine should generally be taken on an empty stomach at least 2 hours before a meal and separated by at least 4 hours from any interacting agents.

来源:DrugBank

吸收、分配和排泄

• 消除途径

甲状腺激素主要通过肾脏消除。一部分结合的激素到达结肠时未发生变化，并随粪便排出。大约20%的T4通过大便排出。随着年龄的增长，T4的尿液排泄量会减少。

Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged and is eliminated in the feces. Approximately 20% of T₄ is eliminated in the stool. Urinary excretion of T₄ decreases with age.

来源:DrugBank

吸收、分配和排泄

循环中的甲状腺激素有超过99%与血浆蛋白结合，包括甲状腺素结合球蛋白（TBG）、甲状腺素结合前白蛋白（TBPA）和白蛋白（TBA），它们对每种激素的容量和亲和力各不相同。TBG和TBPA对T4的高亲和力部分解释了T4与T3相比血清水平更高、代谢清除速度更慢和半衰期更长。与少量游离激素存在反向平衡的蛋白结合甲状腺激素。只有未结合的激素才具有代谢活性。许多药物和生理条件都会影响甲状腺激素与血清蛋白的结合。甲状腺激素不易通过胎盘屏障。

Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), and albumin (TBA), whose capacities and affinities vary for each hormone. The higher affinity of both TBG and TBPA for T4 partially explains the higher serum levels, slower metabolic clearance, and longer half-life of T4 compared to T3. Protein-bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone. Only unbound hormone is metabolically active. Many drugs and physiologic conditions affect the binding of thyroid hormones to serum proteins. Thyroid hormones do not readily cross the placental barrier.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

注射用左旋甲状腺素钠通过静脉给药。给药后，合成的左旋甲状腺素与体内自然分泌的激素无法区分。

Levothyroxine Sodium for Injection is administered via the intravenous route. Following administration, the synthetic levothyroxine cannot be distinguished from the natural hormone that is secreted endogenously.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

口服给药的T4从胃肠道（GI）的吸收率在40%到80%之间。大部分左旋甲状腺素剂量从空肠和近端回肠吸收。与等量口服左旋甲状腺钠溶液相比，Synthroid片剂的相对生物利用度大约为93%。T4的吸收在空腹时增加，在吸收不良综合症和某些食物（如大豆婴儿配方奶粉）中减少。饮食纤维会降低T4的生物利用度。此外，吸收率也可能随着年龄的增长而降低。此外，许多药物和食物都会影响T4的吸收。

Absorption of orally administered T4 from the gastrointestinal (GI) tract ranges from 40% to 80%. The majority of the levothyroxine dose is absorbed from the jejunum and upper ileum. The relative bioavailability of Synthroid tablets, compared to an equal nominal dose of oral levothyroxine sodium solution, is approximately 93%. T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybean infant formula. Dietary fiber decreases bioavailability of T4. Absorption may also decrease with age. In addition, many drugs and foods affect T4 absorption.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险等级：
  IRRITANT
• 危险品标志：
  Xn,F,T
• 安全说明：
  S22,S24/25
• 危险类别码：
  R20/21/22,R40,R11,R23/24/25,R39/23/24/25
• WGK Germany：
  3
• 海关编码：
  2942000000
• 危险品运输编号：
  UN1230 - class 3 - PG 2 - Methanol, solution
• RTECS号：
  YP2833500
• 储存条件：
  应充氩气密封，在阴凉干燥处避光保存。

SDS

Name:	L-Thyroxine 99% Material Safety Data Sheet
Synonym:	None Known
CAS:	51-48-9

Section 1 - Chemical Product MSDS Name:L-Thyroxine 99% Material Safety Data Sheet
Synonym:None Known

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
51-48-9	L-Thyroxine	99%	200-101-1

Hazard Symbols: XN
Risk Phrases: 20/21/22

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Harmful by inhalation, in contact with skin and if swallowed.The toxicological properties of this material have not been fully investigated.Light sensitive.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
No information found.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid if irritation develops or persists. Wash clothing before reuse. Flush skin with plenty of soap and water.
Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion. Runoff from fire control or dilution water may cause pollution.
Extinguishing Media:
In case of fire, use water, dry chemical, chemical foam, or alcohol-resistant foam. Use agent most appropriate to extinguish fire.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Use with adequate ventilation. Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation. Store protected from light.
Storage:
Keep container closed when not in use. Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances. Hormones and antibiotics room. Store protected from light.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Good general ventilation should be sufficient to control airborne levels. Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower.
Exposure Limits CAS# 51-48-9: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to minimize contact with skin.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: cream
Odor: none reported
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: Decomposes
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature: Not available.
Solubility in water: Insoluble in water
Specific Gravity/Density: Not available.
Molecular Formula: C15H11I4NO4
Molecular Weight: 776.6993

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, light, dust generation, excess heat, strong oxidants.
Incompatibilities with Other Materials:
Oxidizing agents, strong bases.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, irritating and toxic fumes and gases, carbon dioxide, nitrogen, hydrogen iodide.
Hazardous Polymerization: Has not been reported.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 51-48-9: YP2833500 LD50/LC50:
Not available.
Carcinogenicity:
L-Thyroxine - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XN
Risk Phrases:
R 20/21/22 Harmful by inhalation, in contact with
skin and if swallowed.
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
S 28A After contact with skin, wash immediately with
plenty of water.
S 37 Wear suitable gloves.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 51-48-9: 1
Canada
CAS# 51-48-9 is listed on Canada's DSL List.
CAS# 51-48-9 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 51-48-9 is listed on the TSCA inventory.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

L-Thyroxine (NSC 36397) 是甲状腺素的合成形式，是一种激素替代药物。

靶点

Human Endogenous Metabolite

体内研究

脱碘酶（DIOs）催化四碘甲腺原氨酸（前体激素）转化为活性甲状腺激素，并与促甲状腺激素 (TSH) 水平相关。DIO1 和 DIO2 促进甲状腺激素的分泌激活，而 DIO3 则负责分泌的失活。DIO1 和 DIO2 的活动在负反馈调节垂体 TSH 分泌中起着关键作用。L-Thyroxine (T4) 和 Triiodothyronine (T3) 能够调节离子通道、泵和调控收缩蛋白的表达。此外，甲状腺激素已被证明影响钙稳态和相关于兴奋和收缩的流量，通过 L-Thyroxine 和 Triiodothyronine 修饰其药理控制与分泌。在喂食12周无碘饮食的大鼠中，Triiodothyronine 和 L-Thyroxine 的水平显著下降（p<0.001）。低剂量L-Thyroxine 治疗组的 L-Thyroxine 水平升高 (p=0.02)，而 Triiodothyronine 水平与对照组相似（p=0.19）。高剂量 L-Thyroxine 治疗组的 Triiodothyronine 和 L-Thyroxine 的血清浓度显著增加，分别相比非治疗性甲减组 (p<0.001) 和对照值 (p=0.03) 显著升高。

化学性质

白色结晶。熔点 235-236℃（分解），比旋光度 [α]^20_D -4.4°（3%，0.13 mol/L 氢氧化钠，70% 乙醇）, 在 0.4 mol/L NaOH溶液中最大吸收波长为 325nm，在 0.4mol/L HCl 溶液中最大吸收波长为 295nm。本品溶于碱溶液，不溶于水、乙醇和乙醚。

用途

生化研究；拟甲状腺素药物。

生产方法

以3,5-二碘-L-酪氨酸为主要原料。

反应信息

• 作为反应物：
  描述：

  甲状腺素 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 0.25h， 生成 L-thyroxine disodium
  参考文献：
  名称：

  [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF LEVOTHYROXINE SODIUM WITH REDUCED LEVELS OF IMPURITIES
  [FR] PROCÉDÉ AMÉLIORÉ POUR LA PRÉPARATION DE LÉVOTHYROXINE SODIQUE PRÉSENTANT DES TAUX RÉDUITS D'IMPURETÉS

  摘要：

  该发明涉及一种改进的工艺，用于制备具有降低杂质水平的左旋甲状腺素钠。该发明还提供了不含3,5-二碘甲状腺原氨酸或甲状腺素d-对映体的左旋甲状腺素钠五水合物。该发明还提供了含有亚甲二碘甲状腺原氨酸低于0.5% wt/wt的左旋甲状腺素钠五水合物。

  公开号：

  WO2009136249A1
• 作为产物：
  描述：

  3,5-二碘-L-酪氨酸 在 氢碘酸 、 溶剂黄146 、 二异丙胺 、 甲胺 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 正丁醇 为溶剂， 反应 12.0h， 生成 甲状腺素
  参考文献：
  名称：

  [EN] NOVEL PROCESS FOR THE PREPARATION OF LEVOTHYROXINE SODIUM
  [FR] NOUVEAU PROCÉDÉ POUR LA PRÉPARATION DE LÉVOTHYROXINE SODIQUE

  摘要：

  该发明提供了一种新型工艺，用于制备高纯度左旋甲状腺素钠，即(S)-2-氨基-3-[4-(4-羟基-3，5-二碘苯氧基)-3,5-二碘苯基]丙酸钠盐，通过两个工艺中间体，即3,5-二碘L-酪氨酸铜络合物和新型双(对甲氧基苯基)碘化物。该发明还提供了不含基因毒性杂质的左旋甲状腺素五水合物，以及甲状腺素水平低于0.04%重量/重量。

  公开号：

  WO2015011573A1
• 作为试剂：
  描述：

  Bis (p-anisyl)iodonium bromide 、 L-thyroxine, sodium salt hexahydrate 、 、 、 N-乙酰基-3,5-二碘-L-酪氨酸乙酯 、 、 、 、 在 铜 作用下， 以 甲状腺素 为溶剂， 以to afford (S)—N-acetyl-3,5-diiodo-4-p-methoxyphenoxyphenylalanine ethyl ester的产率得到N-acetyl-O-(4-methoxyphenyl)-3,5-diiodo-L-tyrosine ethyl ester
  参考文献：
  名称：

  Process for the preparation of levothyroxine sodium

  摘要：

  本发明提供了一种制备高纯左甲状腺素钠的新工艺，即通过两种工艺中间体，即3,5-二碘-L-酪氨酸铜络合物和新型双(对甲氧基苯基)碘离子碘化物，制备(S)-2-氨基-3-[4-(4-羟基-3,5-二碘苯氧基)-3,5-二碘苯基]丙酸钠盐。该发明还提供了不含基因毒性杂质和甲状腺素水平低于0.04%重量/重量的左甲状腺素五水合物。

  公开号：

  US09428444B2

文献信息

• [EN] COMPOUNDS FOR THE TREATMENT OF AMYLOID-ASSOCIATED DISEASES<br/>[FR] COMPOSÉS POUR LE TRAITEMENT DE MALADIES ASSOCIÉES À LA SUBSTANCE AMYLOÏDE
  申请人：REMYND NV

  公开号：WO2016083490A1

  公开（公告）日：2016-06-02

  This invention provides novel compounds of formulae (I) or (II) or a stereoisomer, enantiomer, racemic, or tautomer thereof, (I) (II) wherein the substituents are as defined in the specification. The present invention also relates to the novel compounds for use as a medicine, more in particular for the prevention or treatment of amyloid-related diseases, more specifically certain neurological disorders, such as disorders collectively known as tauopathies, disorders characterized by cytotoxic α-synuclein amyloidogenesis. The present invention also relates to the use of said novel compounds for the manufacture of medicaments useful for treating such amyloid-related diseases. The present invention further relates to pharmaceutical compositions including said novel compounds and to methods for the preparation of said novel compounds.

  这项发明提供了式(I)或(II)或其立体异构体、对映异构体、消旋体或互变异构体的新化合物，其中取代基如规范中所定义。本发明还涉及用作药物的这些新化合物，更具体地用于预防或治疗与淀粉样蛋白相关的疾病，更具体地说是某些神经系统疾病，如被统称为tau病变的疾病，以及由细胞毒性α-突触核蛋白淀粉生成所特征化的疾病。本发明还涉及利用这些新化合物制备对治疗此类淀粉样蛋白相关疾病有用的药物。本发明还涉及包括这些新化合物的药物组合物以及这些新化合物的制备方法。
• Alpha-Ketoamide Inhibitors Of Cysteine Proteases
  申请人：Phelix Therapeutics

  公开号：US20190085024A1

  公开（公告）日：2019-03-21

  The disclosure provides compounds comprising a α-ketoamide linkage that is terminated on each end by an amino acid, such as compounds of Formula (I), wherein RA-RC are defined herein. Also provided are compositions containing these compounds and methods of inhibiting calpain activity, treating a calpain-mediated disorder, inhibiting cathepsin-B, cathepsin-L, cathepsin-S, or cathepsin-L activity, and methods of treating a cathepsin-B, cathepsin-L, cathepsin-S, or cathepsin-L mediated disorder using these compounds and compositions.

  该披露提供了包含α-酮酰胺键的化合物，该键在每端由氨基酸终止，例如式(I)中的化合物，其中RA-RC在此处定义。还提供了含有这些化合物的组合物以及抑制钙蛋白酶活性、治疗钙蛋白酶介导的疾病、抑制卡托普西-B、卡托普西-L、卡托普西-S或卡托普西-L活性的方法，以及使用这些化合物和组合物治疗卡托普西-B、卡托普西-L、卡托普西-S或卡托普西-L介导的疾病的方法。
• [EN] NOVEL COMPOUNDS, THEIR PREPARATION AND USE<br/>[FR] NOUVEAUX COMPOSES, LEUR PREPARATION ET LEUR UTILISATION
  申请人：NOVO NORDISK AS

  公开号：WO2005105736A1

  公开（公告）日：2005-11-10

  Novel compounds of the general formula (I), the use of these compounds as phar- maceutical compositions, pharmaceutical compositions comprising the compounds and methods of treatment employing these compounds and compositions. The present compounds may be useful in the treatment and/or prevention of conditions mediated by Peroxisome Proliferator-Activated Receptors (PPAR), in particular the PPARδ suptype.

  通用公式（I）的新化合物，这些化合物作为药物组成部分的用途，包括这些化合物的药物组成部分和使用这些化合物和组成部分的治疗方法。这些化合物可能在治疗和/或预防由过氧化物酶体增殖物激活受体（PPAR）介导的疾病中有用，特别是PPARδ亚型。
• [EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020257998A1

  公开（公告）日：2020-12-30

  Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.

  提供了一种将细胞毒性药物与一个侧链连接分子结合的共轭物。它提供了制备细胞毒性分子与细胞结合配体的共轭物的侧链连接方法，以及在靶向治疗癌症、感染和免疫性疾病中使用该共轭物的方法。
• [EN] CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES<br/>[FR] DÉRIVÉ DE DIMÈRE DE PYRROLOBENZODIAZÉPINE RÉTICULÉ (PBD) ET SES CONJUGUÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020006722A1

  公开（公告）日：2020-01-09

  A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.

  一种新型的交联细胞毒剂，吡咯苯并二氮杂环二聚体（PBD）衍生物，以及它们与细胞结合分子的结合物，一种制备这些结合物的方法以及这些结合物的治疗用途。

表征谱图