炔雌醇环戊醚 | 152-43-2

• 物质功能分类: 生物 - 细胞培养 - 添加剂
• 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: 炔雌醇环戊醚
• 中文别名: 环戊雌三醇；雌三醇环戊醚；炔雌醚；乙炔雌二醇环戊醚
• 英文名称: quinestrol
• 英文别名: 17α-ethinylestradiol 3-cyclopentyl ether；(8R,9S,13S,14S,17R)-3-cyclopentyloxy-17-ethynyl-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-ol
• CAS: 152-43-2
• 化学式: C₂₅H₃₂O₂
• mdl: MFCD00079189
• 分子量: 364.528
• InChiKey: PWZUUYSISTUNDW-VAFBSOEGSA-N

物化性质

• 熔点：
  107-108°
• 比旋光度：
  D25 +5° (c = 0.5 in dioxane)
• 沸点：
  435.69°C (rough estimate)
• 密度：
  1.0693 (rough estimate)
• 溶解度：
  可溶于氯仿（轻微）、二恶烷（轻微）、DMSO（轻微）、甲醇（轻微）
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

主要代谢为母化合物炔雌醇。炔雌醇在肝脏中代谢。从数量上看，无论是大鼠还是人类，炔雌醇的主要代谢途径是芳香羟基化，这与天然雌激素相同。

Metabolized principally to the parent compound, ethinyl estradiol. Ethinyl estradiol is metabolized in the liver. Quantitatively, the major metabolic pathway for ethinyl estradiol, both in rats and in humans, is aromatic hydroxylation, as it is for the natural estrogens.

来源:DrugBank

代谢

主要代谢为母化合物炔雌醇。炔雌醇在肝脏中代谢。从数量上看，无论是大鼠还是人类，炔雌醇的主要代谢途径是芳香羟基化，这与天然雌激素相同。

Metabolized principally to the parent compound, ethinyl estradiol. Ethinyl estradiol is metabolized in the liver. Quantitatively, the major metabolic pathway for ethinyl estradiol, both in rats and in humans, is aromatic hydroxylation, as it is for the natural estrogens.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

雌激素扩散进入目标细胞并与蛋白质受体（雌激素受体）相互作用。雌激素与目标细胞受体相互作用。当雌激素受体结合了其配体后，它能够进入目标细胞的细胞核，并调节基因转录，从而形成信使RNA。mRNA与核糖体相互作用产生特定的蛋白质，表达雌二醇对目标细胞的效果。雌激素增加了肝脏对性激素结合球蛋白（SHBG）、甲状腺结合球蛋白（TBG）和其他血清蛋白的合成，并抑制了前垂体分泌的促卵泡激素（FSH）。目标细胞包括女性生殖道、乳腺、下丘脑和垂体。雌激素与黄体酮的结合抑制了下丘脑-垂体系统，减少了促性腺激素释放激素（GnRH）的分泌。

Estrogens diffuse into their target cells and interact with a protein receptor (the estrogen receptor). Estrogen interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

副作用包括肝肾功能不全、高血压、心脏病、睾丸退化、早秃和痤疮。

Side effects include liver and kidney dysfunction, high blood pressure, heart disease, degeneration of the testicles, premature baldness, and acne.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

经口服吸收。

Absorbed following oral administration.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

过量症状包括恶心和呕吐，女性可能会出现撤退性出血。

Symptoms of overdose include nausea and vomiting, and withdrawal bleeding may occur in females.

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

• 吸收

经口服吸收。

Absorbed following oral administration.

来源:DrugBank

安全信息

• 危险品标志：
  T
• 危险类别码：
  R20/21/22,R46,R61
• WGK Germany：
  3
• RTECS号：
  RC8948000
• 安全说明：
  S22,S36/37/39,S45,S53
• 储存条件：
  室温

SDS

Revision number: 5
Quinestrol
SAFETY DATA SHEET

---

Section 1. IDENTIFICATION
Quinestrol
Product name:


5
Revision number:

---

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

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substance
Substance/mixture:
Quinestrol
Components:
>97.0%(LC)(T)
Percent:
152-43-2
CAS Number:
17α-Ethynylestradiol 3-Cyclopentyl Ether
Synonyms:
C25H32O2
Chemical Formula:

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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.
Quinestrol

---

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:
A rescuer should wear personal protective equipment, such as rubber gloves and air-
Protection of first-aiders:
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
Use extra personal protective equipment (P3 filter respirator for toxic particles). Keep
Personal precautions,
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
Handling is performed in a well ventilated place. Wear suitable protective equipment.
Technical measures:
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.
Comply with laws.
Packaging material:

---

Section 8. EXPOSURE CONTROLS / PERSONAL PROTECTION
Install a closed system or local exhaust. Also install safety shower and eye bath.
Engineering controls:
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.
Impervious gloves.
Hand protection:
Safety goggles. A face-shield, if the situation requires.
Eye protection:
Skin and body protection: Impervious protective clothing. Protective boots, if the situation requires.

---

Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Solid
Physical state (20°C):
Crystal- Powder
Form:
White - Almost white
Colour:
No data available
Odour:
pH: No data available
Melting point/freezing point:110°C
Quinestrol

---

Section 9. PHYSICAL AND CHEMICAL PROPERTIES
No data available
Boiling point/range:
No data available
Flash point:
Flammability or explosive
limits:
No data available
Lower:
No data available
Upper:
No data available
Relative density:
Solubility(ies):
No data available
[Water]
[Other solvents]
Dioxane
Soluble:

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Section 10. STABILITY AND REACTIVITY
Stable under proper conditions.
Chemical stability:
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
No data available
Acute Toxicity:
Skin corrosion/irritation: No data available
No data available
Serious eye
damage/irritation:
No data available
Germ cell mutagenicity:
Carcinogenicity:
No data available
IARC =
No data available
NTP =
No data available
Reproductive toxicity:
RC8948000
RTECS Number:

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

---

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
Does not correspond to the classification standard of the United Nations
Hazards Class:
Not listed
UN-No:
Quinestrol

---

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

生物活性

quinestrol 是一种合成雌激素，具有在乳腺癌和前列腺癌相关研究中的应用潜力。
用途：作为雌激素类药物使用。

反应信息

• 作为反应物：
  描述：

  炔雌醇环戊醚 在 吡啶 、 苯甲酸 、 三氯氧磷 作用下， 以 2,2,2-三氟乙醇 为溶剂， 反应 67.0h， 生成 2-bromo-6-(((8S,9S,13S,14S)-3-(cyclopentyloxy)-13-methyl-7,8,9,11,12,13,14,15-octahydro-6H-cyclopenta[a]phenanthren-17-yl)ethynyl)-10-methyl-6,7,8,9-tetrahydropyrido[1,2-a]indole
  参考文献：
  名称：

  Development of a Non‐Directed Petasis‐Type Reaction by an Aromaticity‐Disrupting Strategy

  摘要：

  AbstractThe Petasis‐type reaction, which couples an imine and boronic acid, is an important tool for C−C bond formation in organic synthesis. However, the generality of this transformation has been limited by the requirement for a directing heteroatom to enable reactivity. Herein, we report the development of a non‐directed Petasis‐type reaction that allows for the coupling of trifluoroborate salts with α‐hydroxyindoles. By disrupting aromaticity to generate a reactive iminium ion, in conjunction with using trifluoroborate nucleophiles, the method generates a new C−C bond without the need for a directing group. This reaction is operationally simple, providing α‐functionalized indoles in up to 99 % yield using sp, sp2, and sp3‐hybridized trifluoroborate nucleophiles. Finally, this reaction is applied as a novel bioconjugation strategy to link biologically active molecules and toward the convergent synthesis of non‐natural heterodimeric bisindole alkaloid analogs.

  DOI：

  10.1002/anie.202218921
• 作为产物：
  描述：

  19-acetoxyandrosta-1,4-diene-3,17-dione 在 正丁基锂 、 三氟甲磺酸 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 4.0h， 生成 炔雌醇环戊醚
  参考文献：
  名称：

  3-醚化雌酮的环保合成

  摘要：

  常规醚化使用有毒或难降解的烷基化剂。提出了一种生态友好的串联醚化/芳香化反应，以从容易获得的二烯酮1制备雌酮3-仲醚。用该方法从市售的起始原料合成了三种市售的3-醚化雌激素药物。

  DOI：

  10.1016/j.tet.2016.03.002

文献信息

• [EN] TARGETED DRUG DELIVERY THROUGH AFFINITY BASED LINKERS<br/>[FR] ADMINISTRATION CIBLÉE D'UN MÉDICAMENT FAISANT APPEL À DES COUPLEURS FONDÉS SUR L'AFFINITÉ
  申请人：INVICTUS ONCOLOGY PVT LTD

  公开号：WO2015148126A1

  公开（公告）日：2015-10-01

  The current invention discloses targeted drug delivery conjugates comprising a targeting moiety linked to a drug via a molecule having an affinity for the targeting moiety. Typically, the conjugate comprises a targeting ligand and a molecule of interest, e.g., a therapeutic agent. The targeting ligand and the molecule of interest are linked to each other via an affinity ligand. The affinity ligand is further covalently or non-covalently linked to a drug or therapeutic agent. The drug can be modified to make it more soluble and so that it cleaves from the linking molecule at the target site.

  当前的发明揭示了包括通过具有与靶向基团亲和力的分子连接到药物的靶向药物传递共轭物。通常，该共轭物包括一个靶向配体和一个感兴趣的分子，例如，一个治疗剂。靶向配体和感兴趣的分子通过一个亲和配体相互连接。该亲和配体进一步以共价或非共价方式连接到药物或治疗剂。药物可以被修改以使其更溶解，并使其在靶点处从连接分子中解离。
• Oligonucleotides comprising a non-phosphate backbone linkage
  申请人：Manoharan Muthiah

  公开号：US20060287260A1

  公开（公告）日：2006-12-21

  One aspect of the present invention relates to a ribonucleoside substituted with a phosphonamidite group at the 3′-position. In certain embodiments, the phosphonamidite is an alkyl phosphonamidite. Another aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a non-phosphate linkage occurs in only one strand. In certain embodiments, a non-phosphate linkage occurs in both strands. In certain embodiments, a ligand is bound to one of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, a ligand is bound to both of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a ligand is bound to the oligonucleotide strand. In certain embodiments, the oligonucleotide comprises at least one modified sugar moiety.

  本发明的一个方面涉及在3'-位置用磷酰胺基团取代的核糖核苷。在某些实施例中，磷酰胺基团是烷基磷酰胺基团。本发明的另一个方面涉及包含至少一个非磷酸酯连接的双链寡核苷酸。代表性的非磷酸酯连接包括磷酸酯、羟胺、羟基肼基、酰胺和碳酸酯连接。在某些实施例中，非磷酸酯连接是磷酸酯连接。在某些实施例中，非磷酸酯连接仅出现在一条链中。在某些实施例中，非磷酸酯连接出现在两条链中。在某些实施例中，配体结合到包含双链寡核苷酸的寡核苷酸链中的一条链上。在某些实施例中，配体结合到包含双链寡核苷酸的寡核苷酸链中的两条链上。在某些实施例中，寡核苷酸链包含至少一个修饰的糖基团。本发明的另一个方面涉及包含至少一个非磷酸酯连接的单链寡核苷酸。代表性的非磷酸酯连接包括磷酸酯、羟胺、羟基肼基、酰胺和碳酸酯连接。在某些实施例中，非磷酸酯连接是磷酸酯连接。在某些实施例中，配体结合到寡核苷酸链上。在某些实施例中，寡核苷酸包含至少一个修饰的糖基团。
• Oligonucleotides comprising a C5-modified pyrimidine
  申请人：Manoharan Muthiah

  公开号：US20050288244A1

  公开（公告）日：2005-12-29

  One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one ligand. In certain embodiments, a ligand is bound to only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, both of the oligonucleotide strands of the double-stranded oligonucleotide independently comprise a bound ligand. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. In certain embodiments, a phosphate linkage in one or both of the strands of the oligonucleotide has been replaced with a phosphorothioate or phosphorodithioate linkage. In a preferred embodiment, the ligand is cholesterol or 5β-cholanic acid. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one ligand. In certain embodiments, the oligonucleotide comprises at least one modified sugar moiety. In certain embodiments, a phosphate linkage of the oligonucleotide has been replaced with a phosphorothioate or phosphorodithioate linkage. In a preferred embodiment, the ligand is cholesterol or 5β-cholanic acid. The ligand improves the pharmacokinetic properties of the oligonucleotide.

  本发明的一个方面涉及包含至少一个配体的双链寡核苷酸。在某些实施例中，配体仅结合到构成双链寡核苷酸的两个核苷酸链中的一个。在某些实施例中，双链寡核苷酸的两个核苷酸链都独立地包含一个结合的配体。在某些实施例中，核苷酸链包含至少一个修饰的糖基。在某些实施例中，核苷酸链的一个或两个链中的磷酸酯键已被磷硫酸酯或磷二硫酸酯键替代。在一个首选实施例中，配体是胆固醇或5β-胆烷酸。本发明的另一个方面涉及包含至少一个配体的单链寡核苷酸。在某些实施例中，核苷酸包含至少一个修饰的糖基。在某些实施例中，核苷酸的磷酸酯键已被磷硫酸酯或磷二硫酸酯键替代。在一个首选实施例中，配体是胆固醇或5β-胆烷酸。配体改善了寡核苷酸的药代动力学性能。
• Hydroxylated nebivolol metabolites
  申请人：O'Donnell P. John

  公开号：US20070014733A1

  公开（公告）日：2007-01-18

  Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy-6,6′difluoro-, 4-hydroxy-5-phenol-6,6′difluoro-, and 4-hydroxy-8-pheno-6,6′difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof. In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.

  羟基化奈必洛尔代谢物在急性给药后以浓度依赖性方式增加人内皮细胞制剂的一氧化氮释放。此外，羟基化奈必洛尔代谢物，包括但不限于4-羟基-6,6'-二氟代-、4-羟基-5-苯酚-6,6'-二氟代-和4-羟基-8-苯并-6,6'-二氟代-，在慢性给药后能够增加人内皮细胞的一氧化氮释放能力。本发明提供了羟基化奈必洛尔代谢物和包含奈必洛尔和/或至少一种羟基化奈必洛尔代谢物和/或至少一种用于治疗心血管疾病的附加化合物的组合物，以及可药用的盐。此外，本发明还提供了通过给药至少一种能够释放治疗有效量的一氧化氮到受血管疾病影响的靶向部位的羟基化奈必洛尔代谢物来治疗和/或预防血管疾病的方法。本发明还涉及通过给药至少一种羟基化奈必洛尔代谢物来治疗和/或预防偏头痛。本发明还可以与治疗代谢综合征障碍的其他治疗联合使用，或作为单一治疗。
• Nitric Oxide Releasing Prodrugs of Therapeutic Agents
  申请人：SATYAM Apparao

  公开号：US20110263526A1

  公开（公告）日：2011-10-27

  The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents which are represented herein as compounds of formula (I) wherein the drugs or therapeutic agents contain one or more functional groups independently selected from a carboxylic acid, an amino, a hydroxyl and a sulfhydryl group. The invention also relates to processes for the preparation of the nitric oxide releasing prodrugs (the compounds of formula (I)), to pharmaceutical compositions containing them and to methods of using the prodrugs.

  本发明涉及已知药物或治疗剂的一氧化氮释放前药，其在此处表示为式(I)的化合物，其中药物或治疗剂包含一个或多个功能基团，独立地选自羧酸、氨基、羟基和巯基。该发明还涉及制备一氧化氮释放前药（式(I)的化合物）的方法，含有它们的药物组合物以及使用这些前药的方法。