戊酸雌二醇 | 979-32-8

• 物质功能分类: 原料药 - 激素及调节内分泌功能类药 - 雌激素及孕激素类药
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 中文名称: 戊酸雌二醇
• 中文别名: 17-戊酸-17-BETA-雌二酯；3,5(10)-三烯-17B-醇17-戊酸酯；17-戊酸-Beta-雌二醇酯；17-戊酸-β-雌二醇酯；3-羟基雌甾-1,3,5(10)-三烯-17b-醇17-戊酸酯；3-羟基雌甾-1,3,5(10)-三烯-17b-醇 17-戊酸酯
• 英文名称: estradiol 17-valerate
• 英文别名: Estradiol Valerate；[(8R,9S,13S,14S,17S)-3-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] pentanoate
• CAS: 979-32-8
• 化学式: C₂₃H₃₂O₃
• 分子量: 356.505
• InChiKey: RSEPBGGWRJCQGY-RBRWEJTLSA-N

物化性质

• 熔点：
  144°C
• 沸点：
  438.83°C (rough estimate)
• 密度：
  1.1024 (rough estimate)
• 溶解度：
  几乎不溶于水，溶于醇。
• 碰撞截面：
  171 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]
• 稳定性/保质期：

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

外源性雌激素和内源性雌激素通过相同的机制进行代谢。雌激素部分通过细胞色素P450进行代谢。

Exogenous estrogens are metabolized using the same mechanism as endogenous estrogens. Estrogens are partially metabolized by cytochrome P450.

来源:DrugBank

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：戊酸雌二醇在母乳喂养期间尚未进行研究。注射用戊酸雌二醇曾被用来抑制泌乳，通常与睾酮联合使用。一般来说，对于希望哺乳的母亲应避免使用。 口服戊酸雌二醇在美国仅以一种含有二烯诺吉斯特的组合口服避孕产品形式存在。根据现有证据，专家意见认为在母乳喂养期间首选非激素方法，并且在哺乳妇女中，尤其是产后前4周内，建议首选仅含孕激素的避孕药而不是复方口服避孕药。有关更多信息，请咨询有关口服避孕药组合的记录。 ◉ 对哺乳婴儿的影响：截至修订日期，未找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：戊酸雌二醇注射液曾被用作治疗手段来抑制泌乳，通常与睾酮联合使用。 一项回顾性队列研究比较了在青春期接受高剂量雌激素（每天服用3毫克己烯雌酚或150微克炔雌醇）以减少成人身高的371名女性与未接受雌激素的409名女性。两组之间在哺乳持续时间上没有发现差异，这表明青春期使用高剂量雌激素对后来的哺乳没有影响。

◉ Summary of Use during Lactation:Estradiol valerate has not been studied during breastfeeding. Injectable estradiol valerate has been used to suppress lactation, usually in combination with testosterone. Generally, it should be avoided in mothers wishing to breastfeed. Oral estradiol valerate is only available in the United States in a combination oral contraceptive product that also contains dienogest. Based on the available evidence, expert opinion holds that nonhormonal methods are preferred during breastfeeding and progestin-only contraceptives are preferred over combined oral contraceptives in breastfeeding women, especially during the first 4 weeks postpartum. For further information, consult the record entitled, Contraceptives, Oral, Combined. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Estradiol valerate injection was previously used therapeutically to suppress lactation, usually in combination with testosterone. A retrospective cohort study compared 371 women who received high-dose estrogen (either 3 mg of diethylstilbestrol or 150 mcg of ethinyl estradiol daily) during adolescence for adult height reduction to 409 women who did not receive estrogen. No difference in breastfeeding duration was found between the two groups, indicating that high-dose estrogen during adolescence has no effect on later breastfeeding.

来源:Drugs and Lactation Database (LactMed)

吸收、分配和排泄

• 吸收

肌肉注射：当与芳基和烷基团结合用于肌肉注射时，油性制剂的吸收速率会减慢，作用持续时间延长，以至于单次肌注雌二醇戊酸酯或雌二醇环戊酸酯可以在几周内被吸收。Natazia：口服雌二醇戊酸酯后，通过肠道粘膜吸收或首次肝脏通过过程中，分解为17β-雌二醇和戊酸。这会产生雌二醇及其代谢物，雌酮和其他代谢物。在28天序贯疗法的第一天空腹条件下单次吞咽含有3毫克雌二醇戊酸酯的药片后，雌二醇的最大血清浓度为73.3 pg/mL，中位时间大约为6小时（范围为1.5-12小时），雌二醇浓度曲线下的面积[AUC(0-24h)]为1301 pg·h/mL。

IM Injection: When conjugated with aryl and alkyl groups for parenteral administration, the rate of absorption of oily preparations is slowed with a prolonged duration of action, such that a single intramuscular injection of estradiol valerate or estradiol cypionate is absorbed over several weeks. Natazia: After oral administration of estradiol valerate, cleavage to 17β-estradiol and valeric acid takes place during absorption by the intestinal mucosa or in the course of the first liver passage. This gives rise to estradiol and its metabolites, estrone and other metabolites. Maximum serum estradiol concentrations of 73.3 pg/mL are reached at a median of approximately 6 hours (range: 1.5–12 hours) and the area under the estradiol concentration curve [AUC(0–24h)] was 1301 pg·h/mL after single ingestion of a tablet containing 3 mg estradiol valerate under fasted condition on Day 1 of the 28-day sequential regimen.

来源:DrugBank

吸收、分配和排泄

• 消除途径

雌二醇、雌酮和雌三醇与葡萄糖醛酸和硫酸盐结合物一起通过尿液排出。

Estradiol, estrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates.

来源:DrugBank

安全信息

• 危险品标志：
  T
• 安全说明：
  S45,S53
• 危险类别码：
  R60,R61
• WGK Germany：
  3
• 海关编码：
  29372390
• RTECS号：
  KG5793000
• 储存条件：
  室温

SDS

β-Estradiol 17-Valerate
SAFETY DATA SHEET

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Section 1. IDENTIFICATION
Product name: β-Estradiol 17-Valerate

---

Section 2. HAZARDS IDENTIFICATION
GHS classification
PHYSICAL HAZARDS Not classified
HEALTH HAZARDS
Carcinogenicity Category 2
Reproductive toxicity Category 1B
ENVIRONMENTAL HAZARDS Not classified
GHS label elements, including precautionary statements
Pictograms or hazard symbols
Signal word Danger
Hazard statements Suspected of causing cancer
May damage fertility or the unborn child
Precautionary statements:
[Prevention] Obtain special instructions before use.
Do not handle until all safety precautions have been read and understood.
Use personal protective equipment as required.
[Response] IF exposed or concerned: Get medical advice/attention.
[Storage] Store locked up.
[Disposal] Dispose of contents/container through a waste management company authorized by
the local government.

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substance
Substance/mixture:
Components: β-Estradiol 17-Valerate
Percent: >98.0%(GC)
CAS Number: 979-32-8
Chemical Formula: C23H32O3

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Section 4. FIRST AID MEASURES
Remove victim to fresh air and keep at rest in a position comfortable for breathing.
Inhalation:
Get medical advice/attention.
Remove/Take off immediately all contaminated clothing. Gently wash with plenty of
Skin contact:
soap and water. Get medical advice/attention.
β-Estradiol 17-Valerate

---

Section 4. FIRST AID MEASURES
Rinse cautiously with water for several minutes. Remove contact lenses, if present
Eye contact:
and easy to do. Get medical advice/attention.
Get medical advice/attention.Rinse mouth.
Ingestion:
Protection of first-aiders: A rescuer should wear personal protective equipment, such as rubber gloves and air-
tight goggles.

---

Section 5. FIRE-FIGHTING MEASURES
Dry chemical, foam, water spray, carbon dioxide.
Suitable extinguishing
media:
Precautions for firefighters: Fire-extinguishing work is done from the windward and the suitable fire-extinguishing
method according to the surrounding situation is used. Uninvolved persons should
evacuate to a safe place. In case of fire in the surroundings: Remove movable
containers if safe to do so.
When extinguishing fire, be sure to wear personal protective equipment.
Special protective
equipment for firefighters:

---

Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions, Use extra personal protective equipment (P3 filter respirator for toxic particles). Keep
protective equipment and people away from and upwind of spill/leak. Entry to non-involved personnel should
emergency procedures: be controlled around the leakage area by roping off, etc.
Environmental precautions: Prevent product from entering drains.
Methods and materials for Sweep dust to collect it into an airtight container, taking care not to disperse it.
containment and cleaning Adhered or collected material should be promptly disposed of, in accordance with
up: appropriate laws and regulations.

---

Section 7. HANDLING AND STORAGE
Precautions for safe handling
Technical measures: Handling is performed in a well ventilated place. Wear suitable protective equipment.
Prevent dispersion of dust. Wash hands and face thoroughly after handling.
Use a closed system if possible. Use a local exhaust if dust or aerosol will be
generated.
Advice on safe handling: Avoid all contact!
Conditions for safe storage, including any
incompatibilities
Keep container tightly closed. Store in a cool and dark place.
Storage conditions:
Store locked up.
Store away from incompatible materials such as oxidizing agents.
Packaging material: Comply with laws.

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Section 8. EXPOSURE CONTROLS / PERSONAL PROTECTION
Engineering controls: Install a closed system or local exhaust. Also install safety shower and eye bath.
Personal protective equipment
Respiratory protection: Dust respirator, self-contained breathing apparatus(SCBA), supplied air respirator,
etc. Use respirators approved under appropriate government standards and follow
local and national regulations.
Hand protection: Impervious gloves.
Eye protection: Safety goggles. A face-shield, if the situation requires.
Skin and body protection: Impervious protective clothing. Protective boots, if the situation requires.

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Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Physical state (20°C): Solid
Form: Crystal- Powder
Colour: White - Very pale yellow
Odour: Odorless
pH: No data available
Melting point/freezing point:148°C
β-Estradiol 17-Valerate

---

Section 9. PHYSICAL AND CHEMICAL PROPERTIES
No data available
Boiling point/range:
Flash point: No data available
Flammability or explosive
limits:
No data available
Lower:
Upper: No data available
No data available
Relative density:
Solubility(ies):
Insoluble (3.6mg/L, 27°C)
[Water]
[Other solvents]
Ether, Ethanol, Dioxane
Very soluble:
Soluble: Methanol, Chloroform

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Section 10. STABILITY AND REACTIVITY
Chemical stability: Stable under proper conditions.
Possibility of hazardous No special reactivity has been reported.
reactions:
Incompatible materials: Oxidizing agents
Hazardous decomposition Carbon monoxide, Carbon dioxide
products:

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Section 11. TOXICOLOGICAL INFORMATION
Acute Toxicity: No data available
Skin corrosion/irritation: No data available
Serious eye No data available
damage/irritation:
Germ cell mutagenicity: No data available
scu-mus TDLo:400 ug/kg/1W-I
Carcinogenicity:
scu-rat TDLo:104 mg/kg/2Y-I
IARC = No data available
NTP = No data available
Reproductive toxicity: No data available
RTECS Number: KG5793000

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Section 12. ECOLOGICAL INFORMATION
Ecotoxicity:
No data available
Fish:
Crustacea: No data available
No data available
Algae:
Persistence / degradability: No data available
No data available
Bioaccumulative
potential(BCF):
Mobility in soil
Log Pow: No data available
No data available
Soil adsorption (Koc):
Henry's Law No data available
constant(PaM3/mol):

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Section 13. DISPOSAL CONSIDERATIONS
Recycle to process, if possible. Consult your local regional authorities. You may be able to dissolve or mix material
with a 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 14. TRANSPORT INFORMATION
Hazards Class: Does not correspond to the classification standard of the United Nations
Not listed
UN-No:
β-Estradiol 17-Valerate

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Section 15. REGULATORY INFORMATION
Safe management ordinance of dangerous chemical product (State Council announces on January 26, 2002
and revised on February 16,2011): Safe use and production, the storage of a dangerous chemical, transport,
loading and unloading were prescribed.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

用途

戊酸雌二醇是天然雌二醇的戊酸盐，具有雌激素的作用，能促进和调节女性生殖器管及副性征的正常发育，并参与卵巢轴功能的调节。戊酸雌二醇用于治疗闭经、更年期综合症、减少乳汁分泌以及前列腺癌等。

生物活性

Estradiol valerate是一种人工合成的酯，主要用于治疗更年期症状和激素不足。

靶点

Target	Value
ER

体外研究

在MCF-7细胞中，雌二醇（10 nM）在Ser225位点增强了磷酸化作用，表明快速激活鞘氨醇激酶同工酶SphK1。雌二醇（20 nM）刺激了1-磷酸鞘氨醇(S1P)和二氢-S1P从MCF-7细胞的快速释放。SphK1和雌激素受体是S1P 和二氢-S1P形成的主要原因。ABCC1或ABCG2与siRNAs或药理学抑制剂的下调减少了Estradiol (10 nM)介导的S1P 和二氢-S1P从MCF-7细胞的释放。雌二醇（10 nM）抑制了雌激素受体α介导的MCF-7人乳腺癌细胞中miR-21的表达，并通过抑制miR-21的表达激活了MCF-7细胞中几个miR-21靶点基因受体活性。雌二醇（10 nM）增加了MCF-7细胞中内源性miR-21靶基因在蛋白质水平的表达，但不影响RNA水平的表达。

体内研究

在切除卵巢的C57BL/6J小鼠体内，戊酸雌二醇（80 μg/kg/day, s.c.）显著降低了总腹膜细胞和巨噬细胞的绝对数，以双F4/80-和CD11b-阳性着色为特点。切除卵巢的小鼠体内，戊酸雌二醇通过抑制PI3K活性，增强了LPS诱导的TGC引发的巨噬细胞中促炎性细胞因子的表达。戊酸雌二醇的促炎性作用通过下调巯基乙酸盐诱发的巨噬细胞中雌激素受体α的活性而被废止。

用途

用于闭经、更年期综合症，减少乳汁分泌以及前列腺癌等。

反应信息

• 作为反应物：
  描述：

  戊酸雌二醇 以 丙酮 为溶剂， 反应 360.0h， 生成 3,7α-dihydroxyestra-1,3,5(10)-trien-17-one monohydrate
  参考文献：
  名称：

  使用转移的电子密度参数研究了3,7α-二羟基estra-1,3,5（10）-trien-17-一水合物的生物转化，光谱研究，晶体结构和静电性质。

  摘要：

  研究了戊酸雌二醇的生物转化产物，即3,7α-二羟基雌二醇1,3,5（10）-trien-17-1一水合物C 18 H 22 O 3 ·H 2 O，其使用UV-Vis技术进行了研究， IR，1 H和1313 C NMR光谱技术以及质谱分析。根据在100 K下收集的数据，使用单晶X射线衍射确定其晶体结构。使用独立原子模型（IAM）和来自ELMAM2数据库的转移的电子密度参数对结构进行精制。该结构通过氢键和范德华相互作用网络稳定。氢键的拓扑结构已通过“分子中的原子”框架的Bader理论进行了分析。转移的多极原子模型的分子静电势揭示了由于分子内大量的电荷离域而导致的跨分子电荷分布的不对称特性。还计算了分子偶极矩，这表明该分子具有强极性特征。

  DOI：

  10.1107/s2053229618004953
• 作为产物：
  描述：

  3-benzoyloxy-17β-valeryloxy-estra-1,3,5(10)-triene 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成 戊酸雌二醇
  参考文献：
  名称：

  制备一些雌三醇酯。

  摘要：

  通过将雌三醇与羧酸一起回流或加热，可从雌三醇（I）中获得雌三醇 16-单乙酸酯。在更苛刻的条件下，可以得到雌三醇 16、17-二乙酸酯。酯交换反应也得到了相同的结果。雌三醇三乙酸酯和雌二醇二乙酸酯与硼氢化钠反应，分别生成雌三醇 16、17-二乙酸酯和雌二醇 17-乙酸酯。3，16α-二羟基雌甾-1，3，5 (10)-三烯-17-酮二乙酸酯（III）经硼氢化钠处理转化为雌三醇 16-乙酸酯（IIa）。在较温和的条件下，可得到雌三醇 3，16-二乙酸酯（VI）。

  DOI：

  10.1248/cpb.11.510

文献信息

• Heterocyclic derivatives for the treatment of cancer and other proliferative diseases
  申请人：——

  公开号：US20020143182A1

  公开（公告）日：2002-10-03

  The invention relates to certain heterocyclic compounds useful for the treatment of cancer and other diseases, having the Formula (I): 1 wherein: (a) m is an integer 0 or 1; (b) R 12 is an alkyl, a substituted alkyl, a cycloalkyl, a substituted cycloalkyl, a heterocyclic, a substituted heterocyclic, a heteroaryl, a substituted heteroaryl, an aryl or a substituted aryl residue; (c) Ar 3 is an aryl, a substituted aryl, a heteroaryl or a substituted heteroaryl residue; (d) Ar 4 is an aryl, a substituted aryl, a heteroaryl or a substituted heteroaryl residue; (e) R 5 is hydrogen, hydroxy, alkyl or substituted alkyl; (f) - - - - - represents a bond present or absent; and (g) W, X, Y and Z are independently or together C(O)—, C(S), S, O, or NH; or a pharmaceutically acceptable salt thereof.

  该发明涉及某些对治疗癌症和其他疾病有用的杂环化合物，其具有以下式（I）： 1 其中： (a) m是整数0或1； (b) R12是烷基，取代烷基，环烷基，取代环烷基，杂环基，取代杂环基，杂芳基，取代杂芳基，芳基或取代芳基残基； (c) Ar3是芳基，取代芳基，杂芳基或取代杂芳基残基； (d) Ar4是芳基，取代芳基，杂芳基或取代杂芳基残基； (e) R5是氢，羟基，烷基或取代烷基； (f) - - - - - 代表存在或不存在的键；以及 (g) W、X、Y和Z独立或一起是C(O)、C(S)、S、O或NH；或其药学上可接受的盐。
• Gold catalyzed efficient preparation of dihydrobenzofuran from 1,3-enyne and phenol
  作者：Yu-Jiang Wang、Yuan Zhang、Zou Qiang、Jia-Ying Liang、Zili Chen

  DOI：10.1039/d1cc05260h

  日期：——

  A gold catalyzed formal intermolecular [2+3] cyclo-coupling of 1,3-enynes with phenols was developed to prepare dihydrobenzofuran derivatives with the addition of 2,6-dichloropyridine N-oxide, in which, a highly ortho-selective phenol SEAr functionalization was achieved by using 1,3-enynes as α-oxo vinyl gold carbenoid surrogates.

  开发了金催化的 1,3-烯炔与苯酚的正式分子间 [2+3] 环偶联，通过添加 2,6-二氯吡啶N-氧化物制备二氢苯并呋喃衍生物，其中，高度邻位选择性的苯酚 S E Ar 官能化是通过使用 1,3-烯炔作为 α-氧代乙烯基金卡宾酸替代物来实现的。
• [EN] AMIDOIMIDAZOPYRIDAZINES AS MKNK-1 KINASE INHIBITORS<br/>[FR] AMIDOIMIDAZOPYRIDAZINES À TITRE D'INHIBITEURS DE KINASES MKNK-1
  申请人：BAYER PHARMA AG

  公开号：WO2014118135A1

  公开（公告）日：2014-08-07

  The present invention relates to amido-substituted imidazopyridazine compounds of general formula (I) : in which A, R1, R2, R3, R4 and n are as defined in the claims, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper- proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients.

  本发明涉及一般式(I)的酰胺取代咪唑吡啶化合物，其中A、R1、R2、R3、R4和n如权利要求中所定义，以及制备所述化合物的方法，用于制备所述化合物的有用中间体化合物，包括所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗或预防疾病的药物组合物，特别是用作唯一药剂或与其他活性成分结合。
• SELF-ASSEMBLY OF THERAPEUTIC AGENT-PEPTIDE NANOSTRUCTURES
  申请人：Ohio State Innovation Foundation

  公开号：US20140155577A1

  公开（公告）日：2014-06-05

  Disclosed are conjugates of hydrophobic drugs linked to protected or unprotected amino acids or peptides. The disclosed conjugates are amphiphilic and can self assemble into nanotubes. Nanotubes comprising the conjugates are also described and can have high loading of the drug and protect it from degradation or elimination. The nanotubes are well suited to deliver hydrophobic and unstable drugs to individuals.

  揭示了与受保护或未受保护的氨基酸或肽连接的疏水药物的共轭物。所述的共轭物是两性的，可以自组装成纳米管。还描述了包含这些共轭物的纳米管，可以具有高药物载荷并保护药物免受降解或排泄。这些纳米管非常适合向个体输送疏水和不稳定的药物。
• HETEROAROMATIC COMPOUNDS FOR USE AS HIF INHIBITORS
  申请人：Härter Michael

  公开号：US20110301122A1

  公开（公告）日：2011-12-08

  The present application relates to novel substituted aryl compounds, processes for their preparation, their use for treatment and/or prevention of diseases and their use for the preparation of medicaments for treatment and/or prevention of diseases, in particular for treatment and/or prevention of hyperproliferative and angiogenic diseases and those diseases which arise from metabolic adaptation to hypoxic states. Such treatments can be carried out as monotherapy or also in combination with other medicaments or further therapeutic measures.

  本申请涉及新型取代芳基化合物，其制备方法，它们用于治疗和/或预防疾病以及用于制备治疗和/或预防疾病的药物，特别是用于治疗和/或预防过度增殖和血管生成性疾病以及那些由于代谢适应缺氧状态而引起的疾病。这种治疗可以作为单独治疗进行，也可以与其他药物或进一步的治疗措施结合使用。