氟尼缩松 | 3385-03-3

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 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: 氟尼缩松
• 中文别名: 6-氟-11,16Α,17,21-四羟基孕-1,4-二烯-3,20-二酮-16,17-安奈德
• 英文名称: flunisolide
• 英文别名: (1S,2S,4R,8S,9S,11S,12S,13R,19S)-19-fluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one
• CAS: 3385-03-3
• 化学式: C₂₄H₃₁FO₆
• 分子量: 434.505
• InChiKey: XSFJVAJPIHIPKU-XWCQMRHXSA-N

物化性质

• 熔点：
  237-240°C (dec.)
• 沸点：
  581.8±50.0 °C(Predicted)
• 密度：
  1.1517 (estimate)
• 溶解度：
  DMF：30mg/mL； DMSO：30mg/mL；乙醇：30mg/mL；乙醇:PBS (pH 7.2) (1:2): 0.2 mg/mL
• 物理描述：
  Solid
• 碰撞截面：
  199.8 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]
• 稳定性/保质期：
  在常温常压下保持稳定

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  7

ADMET

代谢

主要在肝脏中，转化为S型β-羟基代谢物。

Primarily hepatic, converted to the S beta-OH metabolite.

来源:DrugBank

毒理性

• 在妊娠和哺乳期间的影响

哺乳期使用总结：尽管没有进行测量，吸入型皮质类固醇被母体吸收进入血液和分泌到母乳中的量可能太小，不足以影响哺乳的婴儿。审阅者和专家小组认为吸入型和口服型皮质类固醇在哺乳期间使用是可以接受的。 ◉ 对哺乳婴儿的影响：任何皮质类固醇都没有报告有影响。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:Although not measured, the amounts of inhaled corticosteroids absorbed into the maternal bloodstream and excreted into breastmilk are probably too small to affect a breastfed infant. Reviewers and an expert panel consider inhaled and oral corticosteroids acceptable to use during breastfeeding. ◉ Effects in Breastfed Infants:None reported with any corticosteroid. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 蛋白质结合

大约40%，在口服吸入后

Approximately 40% after oral inhalation

来源:DrugBank

吸收、分配和排泄

• 吸收

迅速吸收

Absorbed rapidly

来源:DrugBank

安全信息

• 危险品运输编号：
  UN 2811 6.1 / PGI
• WGK Germany：
  3
• RTECS号：
  TU3900000
• 储存条件：
  常温下应存放在避光、通风干燥处，并密封保存。

SDS

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Section 1. Chemical Product and Company Identification
Flunisolide, Anhydrous
Common Name/
Trade Name
Flunisolide, Anhydrous

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Section 4. 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. Cover the irritated skin with an emollient. Remove
contaminated clothing and shoes. Wash clothing before reuse. Thoroughly clean shoes before reuse. Get
medical attention.
Serious Skin Contact Wash with a disinfectant soap and cover the contaminated skin with an anti-bacterial cream. Seek immediate
medical attention.
Inhalation If inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get
medical attention.
Serious Inhalation Evacuate the victim to a safe area as soon as possible. Loosen tight clothing such as a collar, tie, belt or
waistband. Seek medical attention.
Ingestion If swallowed, do not induce vomiting unless directed to do so by medical personnel. Never give anything by
mouth to an unconscious person. Loosen tight clothing such as a collar, tie, belt or waistband. Get medical
attention immediately.
Serious Ingestion Not available.

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Section 5. Fire and Explosion Data
Flammability of the Product May be combustible at high temperature.
Auto-Ignition Temperature Not available.
Flash Points Not available.
Flammable Limits Not available.
Products of Combustion These products are carbon oxides (CO, CO2), halogenated compounds.
Fire Hazards in Presence of Slightly flammable to flammable in presence of heat.
Various Substances Non-flammable in presence of shocks.
Explosion Hazards in Presence Risks of explosion of the product in presence of mechanical impact: Not available.
of Various Substances Risks of explosion of the product in presence of static discharge: Not available.
Fire Fighting Media SMALL FIRE: Use DRY chemical powder.
and Instructions LARGE FIRE: Use water spray, fog or foam. Do not use water jet.
Special Remarks on Not available.
Fire Hazards
Special Remarks on Explosion Not available.
Hazards

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Section 6. Accidental Release Measures
Small Spill Use appropriate tools to put the spilled solid in a convenient waste disposal container.
Large Spill Poisonous solid.
Stop leak if without risk. Do not get water inside container. Do not touch spilled material. Use water spray to
reduce vapors. Prevent entry into sewers, basements or confined areas; dike if needed. Eliminate all ignition
Flunisolide, Anhydrous

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Section 7. Handling and Storage
Precautions Keep locked up.. Keep away from heat. Keep away from sources of ignition. Empty containers pose a fire risk,
evaporate the residue under a fume hood. Ground all equipment containing material. Do not ingest. Do not
breathe dust. Wear suitable protective clothing. In case of insufficient ventilation, wear suitable respiratory
equipment. If ingested, seek medical advice immediately and show the container or the label. Avoid contact with
skin and eyes.
Storage Keep container tightly closed. Keep container in a cool, well-ventilated area. Do not store above 25°C (77°F).

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Section 8. 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 Splash goggles. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent.
Gloves.
Personal Protection in Case of Splash goggles. Full suit. Dust respirator. Boots. Gloves. A self contained breathing apparatus should be used
a Large Spill 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 9. Physical and Chemical Properties
Physical state and appearance Solid. Odor Not available.
Not available.
Taste
Molecular Weight 434.51 g/mole
Not available.
Color
Not available.
pH (1% soln/water)
Boiling Point Not available.
Not available.
Melting Point
Critical Temperature Not available.
Specific Gravity Not available.
Vapor Pressure Not applicable.
Vapor Density Not available.
Not available.
Volatility
Odor Threshold Not available.
Water/Oil Dist. Coeff. Not available.
Ionicity (in Water) Not available.
Dispersion Properties Not available.
Solubility Not available.

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Section 10. Stability and Reactivity Data
Stability The product is stable.
Instability Temperature Not available.
Conditions of Instability Excess heat
Incompatibility with various Not available.
substances
Flunisolide, Anhydrous
Corrosivity Not available.
Special Remarks on Not available.
Reactivity
Special Remarks on Not available.
Corrosivity
Polymerization Will not occur.

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Section 11. Toxicological Information
Routes of Entry Inhalation. Ingestion.
Toxicity to Animals Acute oral toxicity (LD50): >0.5 mg/kg [Mouse].
Chronic Effects on Humans Not available.
Other Toxic Effects on Hazardous in case of skin contact (irritant), of ingestion, of inhalation.
Humans
Special Remarks on Not available.
Toxicity to Animals
Special Remarks on May cause adverse reproductive effects (paternal and maternal effects, fetotoxicity) and birth defects based on
Chronic Effects on Humans animal data. No human data found at this time.
Special Remarks on other Acute Potential Health Effects:
Toxic Effects on Humans Skin: May cause skin irritation.
Eyes: May cause eye irritation.
Inhalation: May cause respiratory tract irritation. May cause ulceration of nasal septum.
Ingestion: Harmful if swallowed. May cause gastrointestinal tract irritation. May affect behavior/Central Nervous
system (somnolence). May also affect metabolism (weight loss or decreased weight gain),and blood(aplastic
anemia).

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Section 12. Ecological Information
Ecotoxicity Not available.
BOD5 and COD Not available.
Products of Biodegradation Possibly hazardous short term degradation products are not likely. However, long term degradation products may
arise.
Toxicity of the Products The products of degradation are as toxic as the product itself.
of Biodegradation
Not available.
Special Remarks on the
Products of Biodegradation

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Section 13. Disposal Considerations
Waste Disposal Waste must be disposed of in accordance with federal, state and local environmental
control regulations.
Flunisolide, Anhydrous

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Section 14. Transport Information
DOT Classification CLASS 6.1: Poisonous material.
Identification : Toxic Solid, Organic, n.o.s. (Flunisolide) UNNA: 2811 PG: III
Not available.
Special Provisions for
Transport
DOT (Pictograms)
HARMFUL
STOW AWAY
FROM
FOODSTUFFS
6

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Section 15. Other Regulatory Information and Pictograms
California prop. 65: This product contains the following ingredients for which the State of California has found to
Federal and State
cause cancer, birth defects or other reproductive harm, which would require a warning under the statute:
Regulations
Flunisolide, Anhydrous
California prop. 65: This product contains the following ingredients for which the State of California has found to
cause reproductive harm (female) which would require a warning under the statute: Flunisolide, Anhydrous
California prop. 65: This product contains the following ingredients for which the State of California has found to
cause birth defects which would require a warning under the statute: Flunisolide, Anhydrous
California
California prop. 65: This product contains the following ingredients for which the State of California has found
Proposition 65
to cause birth defects which would require a warning under the statute: Flunisolide, Anhydrous
Warnings
Other Regulations OSHA: Hazardous by definition of Hazard Communication Standard (29 CFR 1910.1200).
EINECS: This product is on the European Inventory of Existing Commercial Chemical Substances.
WHMIS (Canada) Not controlled under WHMIS (Canada).
Other Classifications
DSCL (EEC) R28- Very toxic if swallowed. S1/2- Keep locked up and out of the reach of
R36/38- Irritating to eyes and skin. children.
S28- After contact with skin, wash immediately
with plenty of water.
S36/37- Wear suitable protective clothing and
gloves.
S45- In case of accident or if you feel unwell,
seek medical advice immediately (show the
label where possible).
S46- If swallowed, seek medical advice
immediately and show this container or label.
Health Hazard
HMIS (U.S.A.) 2 National Fire Protection
1 Flammability
1 Association (U.S.A.)
Fire Hazard
2 0 Reactivity
Health
Reactivity
0
Specific hazard
Personal Protection
E
WHMIS (Canada)
(Pictograms)
DSCL (Europe)
(Pictograms)
Flunisolide, Anhydrous
TDG (Canada)
(Pictograms)
6
ADR (Europe)
(Pictograms)
Protective Equipment
Gloves.
Lab coat.
Dust respirator. Be sure to use an
approved/certified respirator or
equivalent.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

Flunisolide 是一种皮质类固醇，常用于过敏性鼻炎的研究。其主要作用机制是激活糖皮质激素受体，这意味着 Flunisolide 具有显著的抗炎效果。

反应信息

• 作为反应物：
  描述：

  氟尼缩松 在 Wilkinson's catalyst 、 氢气 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 65.0h， 以76%的产率得到氟氢缩松
  参考文献：
  名称：

  6α-Fluoro- 和 6α,9α-difluoro-11β,21-dihydroxy-16α,17α-propylmethylenedioxypregn-4-ene-3,20-dione：合成和评价其 C-22 差向异构体的活性和动力学

  摘要：

  摘要 人们普遍认为，糖皮质激素的抗炎作用与其在受体水平上的不良反应是分不开的。然而，通过结构改变来改变药代动力学可以为类固醇提供比目前使用的更好的治疗指数。因此，合成并研究了丁醛和 6α-氟-或 6α,9α-二氟-16α-羟基皮质醇之间的新 16α,17α-缩醛。相应的 16α,17α-二醇的缩醛化或它们的 16α,17α-丙酮化物在二恶烷中的转缩醛化产生 C-22 差向异构体的混合物，这些混合物通过制备色谱法进行拆分。或者，通过在存在惰性材料的烃中进行缩醛化和转缩醛化，使用一种有效的方法立体选择性地生产 22R-差向异构体。(22R)-6α,9α-difluoro-11β,21-dihydroxy-16α,17α-propylmethylenedioxypregn-4-ene-3,20-dione 的 C-22 构型通过单晶 X 射线衍射明确确定。本发明化合物，尤其是刚刚提到的22R-差

  DOI：

  10.1016/s0039-128x(97)00107-4
• 作为产物：
  描述：

  泼尼松杂质5 在 高氯酸 、 甲烷磺酸 、 chromium(III) chloride hexahydrate 、 巯基乙酸 、 sodium hydroxide 、 锌 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.5h， 生成 氟尼缩松
  参考文献：
  名称：

  [EN] NOVEL PROCESS FOR PREPARATION OF GLUCOCORTICOID STEROIDS
  [FR] NOUVEAU PROCÉDÉ DE PRÉPARATION DE STÉROÏDES DE TYPE GLUCOCORTICOÏDE

  摘要：

  本发明揭示了一种制备16,17-孕烷衍生物的16,17-缩醛的方法，其具有式(I)的结构，其中每个取代基独立地选择自; R1为H或CH3; R2为C1-C6直链或支链烷基，炔基或环烷基; 芳基或杂环芳基; 或R1和R2结合形成饱和的、不饱和的C3-C6环或杂环环; R3和R4相同或不同，每个独立地表示H或卤素; R5为-OH或-OCOR，其中R表示H或C1-C6直链、支链或环烷基，可能被取代。

  公开号：

  WO2016120891A1

文献信息

• DISUBSTITUTED TRIFLUOROMETHYL PYRIMIDINONES AND THEIR USE
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US20160221965A1

  公开（公告）日：2016-08-04

  The present application relates to novel 2,5-disubstituted 6-(trifluoromethyl)pyrimidin-4(3H)-one derivatives, to processes for their preparation, to their use alone or in combinations for the treatment and/or prevention of diseases, and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for treatment and/or prevention of cardiovascular, renal, inflammatory and fibrotic diseases.

  本申请涉及新颖的2,5-二取代6-(三氟甲基)嘧啶-4(3H)-酮衍生物，其制备方法，其单独或与其他药物联合用于治疗和/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/或预防心血管、肾脏、炎症和纤维化疾病。
• [EN] 3,5-DIAMINO-6-CHLORO-N-(N-(4-PHENYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2- CARBOXAMIDE COMPOUNDS<br/>[FR] COMPOSÉS 3,5-DIAMINO -6-CHLORO-N-(N- (4-PHÉNYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2-CARBOXAMIDE
  申请人：PARION SCIENCES INC

  公开号：WO2014099673A1

  公开（公告）日：2014-06-26

  The present invention relates compounds of the formula: or pharmaceutically acceptable salts thereof, useful as sodium channel blockers, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, bronchiectasis, acute and chronic bronchitis, emphysema, and pneumonia.

  本发明涉及以下化合物的公式：或其药学上可接受的盐，用作钠通道阻滞剂，以及含有这些化合物的组合物，制备这些化合物的方法，以及在促进粘膜表面水合和治疗包括囊性纤维化、慢性阻塞性肺病、哮喘、支气管扩张、急性和慢性支气管炎、肺气肿和肺炎等疾病的治疗方法。
• CHLORO-PYRAZINE CARBOXAMIDE DERIVATIVES WITH EPITHELIAL SODIUM CHANNEL BLOCKING ACTIVITY
  申请人：Parion Sciences, Inc.

  公开号：US20140171447A1

  公开（公告）日：2014-06-19

  This invention provides compounds of the formula I: and their pharmaceutically acceptable salts, useful as sodium channel blockers, compositions containing the same, therapeutic methods and uses for the same and processes for preparing the same.

  这项发明提供了式I的化合物及其药用盐，可用作钠通道阻滞剂，包含这些化合物的组合物，以及用于这些化合物的治疗方法和用途，以及制备这些化合物的方法。
• Dual Pharmacophores - PDE4-Muscarinic Antagonistics
  申请人：Callahan James Francis

  公开号：US20090203657A1

  公开（公告）日：2009-08-13

  The present invention is directed to novel compounds of Formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use as dual chromaphores having inhibitory activity against PDE4 and muscarinic acetylcholine receptors (mAChRs), and thus being useful for treating respiratory diseases.

  本发明涉及具有式（I）的新化合物及其药用盐，药物组合物及其用作对PDE4和肌胆碱受体（mAChRs）具有抑制活性的双色素，因此可用于治疗呼吸道疾病。
• [EN] DUAL PHARMACOPHORES - PDE4-MUSCARINIC ANTAGONISTICS<br/>[FR] PHARMACOPHORES DUALS, ANTAGONISTES DES RÉCEPTEURS MUSCARINIQUES ET INHIBITEURS DE L'ACTIVITÉ PDE4
  申请人：GLAXO GROUP LTD

  公开号：WO2009100169A1

  公开（公告）日：2009-08-13

  The present invention is directed to novel compounds of Formula's (I) - (VI), and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use in therapy, for example as inhibitors of phosphodiesterase type IV (PDE4) and as antagonists of muscarinic acetylcholine receptors (mAChRs), in the treatment of and/or prophylaxis of respiratory diseases, including inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis (e.g. allergic rhinitis), atopic dermatitis or psoriasis.

  本发明涉及式(I) - (VI)的新化合物，以及其药学上可接受的盐、药物组合物及其在治疗中的应用，例如作为磷酸二酯酶IV (PDE4)的抑制剂和肌碱乙酰胆碱受体 (mAChRs)的拮抗剂，用于治疗和/或预防呼吸道疾病，包括炎症性和/或过敏性疾病，如慢性阻塞性肺病（COPD）、哮喘、鼻炎（例如过敏性鼻炎）、特应性皮炎或银屑病。