倍氯米松 | 4419-39-0

• 物质功能分类: 原料药 - 激素及调节内分泌功能类药 - 肾上腺皮质激素类药
• 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: 倍氯米松
• 中文别名: 倍氯美松；9α-氯-11β,17α,21-三羟基-16β-甲基孕甾-1,4-二烯-3,20-二酮；9α-氯-16β-甲基孕甾-1,4-二烯-11β,17α,21-三醇-3,20-二酮
• 英文名称: beclomethasone
• 英文别名: 11β,17α,21-trihydroxy-9α-chloro-16β-methylpregna-1,4-diene-3,20-dione；beclometasone；9-chloro-11β,17,21-trihydroxy-16β-methyl-pregna-1,4-diene-3,20-dione；9-chloro-11β,17,21-trihydroxy-16β-methyl-pregna-1,4 diene-3,20-dione；beclomethazone；(8S,9R,10S,11S,13S,14S,16S,17R)-9-chloro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one
• CAS: 4419-39-0
• 化学式: C₂₂H₂₉ClO₅
• 分子量: 408.922
• InChiKey: NBMKJKDGKREAPL-DVTGEIKXSA-N

物化性质

• 熔点：
  217- 222°C (dec.)
• 沸点：
  600.2±55.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)
• 溶解度：
  二恶烷（少量，超声处理）、DMSO（少量溶解）、乙酸乙酯（少量溶解）、甲烷
• 碰撞截面：
  189.2 Ų [M+H]+ [CCS Type: TW]

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  94.8
• 氢给体数：
  3
• 氢受体数：
  5

ADMET

毒理性

• 在妊娠和哺乳期间的影响

母乳喂养期间使用总结：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排入母乳中的量可能太小，不足以影响哺乳的婴儿。专家意见认为，吸入和口服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：目前没有报告任何皮质类固醇对哺乳婴儿有影响。有三名婴儿在母亲通过吸入器使用倍氯米松双丙酸酯治疗期间，被哺乳了6个月。 ◉ 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. Expert opinion considers inhaled and oral corticosteroids acceptable to use during breastfeeding. ◉ Effects in Breastfed Infants:None reported with any corticosteroid. Three infants were breastfed for 6 months during maternal treatment with beclomethasone dipropionate by inhaler. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

安全信息

• 安全说明：
  S24/25
• WGK Germany：
  3
• 海关编码：
  29372900
• 危险品运输编号：
  NONH for all modes of transport
• 储存条件：
  2-8℃

SDS

---

Section 1. Chemical Product and Company Identification
Beclomethasone
Common Name/
Trade Name
Beclomethasone

---

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 if irritation occurs.
Skin Contact Wash with soap and water. Cover the irritated skin with an emollient. Get medical attention if irritation develops.
Serious Skin Contact Not available.
Inhalation If inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get
medical attention.
Serious Inhalation Not available.
Ingestion Do NOT induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an
unconscious person. If large quantities of this material are swallowed, call a physician immediately. Loosen tight
clothing such as a collar, tie, belt or waistband.
Serious Ingestion Not available.

---

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
Explosion Hazards in Presence 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.
of Various Substances
SMALL FIRE: Use DRY chemical powder.
Fire Fighting Media
and Instructions LARGE FIRE: Use water spray, fog or foam. Do not use water jet.
As with most organic solids, fire is possible at elevated temperatures
Special Remarks on
Fire Hazards
Special Remarks on Explosion Fine dust dispersed in air in sufficient concentrations, and in the presence of an ignition source is a potential dust
Hazards explosion hazard.

---

Section 6. Accidental Release Measures
Small Spill Use appropriate tools to put the spilled solid in a convenient waste disposal container. Finish cleaning by
spreading water on the contaminated surface and dispose of according to local and regional authority
requirements.
Large Spill Use a shovel to put the material into a convenient waste disposal container. Finish cleaning by spreading water
on the contaminated surface and allow to evacuate through the sanitary system.
Beclomethasone

---

Section 7. Handling and Storage
Precautions Keep away from heat. Keep away from sources of ignition. Ground all equipment containing material. Do not
breathe dust.
Storage Keep container tightly closed. Keep container in a cool, well-ventilated area. Do not store above 8°C (46.4°F).
Refrigerate.

---

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
Safety glasses. Lab coat. Dust respirator. Use a dust respirator if ventilation is inadequate and handling of
product creates visible dust clouds. 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.

---

Section 9. Physical and Chemical Properties
Physical state and appearance Solid. (Solid powder.) Odor Not available.
Taste Not available.
Molecular Weight 408.92 g/mole
Color White.
pH (1% soln/water) Not available.
Boiling Point Not available.
Melting Point 198°C (388.4°F)
Critical Temperature Not available.
Not available.
Specific Gravity
Vapor Pressure Not applicable.
Vapor Density Not available.
Volatility Not available.
Odor Threshold Not available.
Not available.
Water/Oil Dist. Coeff.
Ionicity (in Water) Not available.
Not available.
Dispersion Properties
Solubility Not available.

---

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

---

Section 11. Toxicological Information
Routes of Entry Inhalation. Ingestion.
Toxicity to Animals LD50: Not available.
LC50: Not available.
Chronic Effects on Humans Not available.
Other Toxic Effects on Slightly hazardous in case of skin contact (irritant), of ingestion, of inhalation.
Humans
Special Remarks on Not available.
Toxicity to Animals
Special Remarks on
Not available.
Chronic Effects on Humans
Special Remarks on other Acute Potential Health Effects:
Toxic Effects on Humans Skin: May cause skin irritation.
Eyes: Dust may cause eye irritation.
Inhalation: A massive single dose is unlikely to cause adverse effects. Dust may cause respiratory tract
(nasopharyngeal) irritaiton with nasopharyngitis, nasal burning, rhinorrhea, hoarseness, bronchospasm, coughing
and possible nasal septum perforation. It may also cause headache, nausea, vomiting.
Ingestion: May cause gastrointestinal tract irritation with nausea, vomiting.
Other adverse effects of inhalation or ingestion may include: decreased or blurred vision, frequent urination,
increased thirst, increased appetite, indegestion, nervousness, trouble sleeping weight gain, dizziness, flushing of
the face or cheeks, hiccups, and increased sweating.
Chronic Potential Health Effects:
Inhalation or Ingestion: Prolonged or repeated inhalation or ingestion may cause possible hypersensitization; acne
or other skin problems; hip or shoulder pain; osteoporosis; gradual blurring or loss of vision (cataracts or
glaucoma); eye pain or redness; tearing and sensitivity of eyes to light; rounding out of the face; purple lines on
arms, face, legs, trunk, groin; unusual increase in hair growth; hypertension; menstrual irregularities; muscle
weakness; unusual bruising; rapid weight gain; swelling of feet or lower legs; irregular heartbeat; muscle cramps
or pain; unusual tiredness or weakness; impaired wound healing; headache; insomnia; pain in back, ribs, arms or
legs; continuing abdominal or stomach pain or burning; nausea; vomiting; bloody or black tarry stools; tendon
rupture; thin, fragile skin.
Medical Conditions Aggravated by Exposure: Hypersensitivity to material; ocular herpes simplex; AIDS or HIV
infection; heart disease; congestive heart failure; recent heart attack; intestinal anastomoses; strongyloides
infestation; diabetes mellitus; mayasthenia gravis; impaired kidney function or disease; esophagitis; gastritis or
peptic ulcer; chicken pox or measles (including recent exposure); tuberculosis; system fungal infections.

---

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 more toxic than the product itself.
of Biodegradation
Special Remarks on the Not available.
Products of Biodegradation
Beclomethasone

---

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

---

Section 14. Transport Information
DOT Classification Not a DOT controlled material (United States).
Not applicable.
Identification
Not applicable.
Special Provisions for
Transport
DOT (Pictograms)

---

Section 15. Other Regulatory Information and Pictograms
No products were found.
Federal and State
Regulations
California California prop. 65: This product contains the following ingredients for which the State of California has found
to cause cancer which would require a warning under the statute: No products were found.
Proposition 65
Warnings
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: No products were found.
Other Regulations EINECS: This product is on the European Inventory of Existing Commercial Chemical Substances. EINECS no.
224-585-9.
WHMIS (Canada) Not controlled under WHMIS (Canada).
Other Classifications
DSCL (EEC) This product is not classified according Not applicable.
to the EU regulations.
Health Hazard
HMIS (U.S.A.) 1 National Fire Protection
1 Flammability
1 Association (U.S.A.)
Fire Hazard
1 0 Reactivity
Health
Reactivity
0
Specific hazard
Personal Protection
E
WHMIS (Canada)
(Pictograms)
DSCL (Europe)
(Pictograms)
TDG (Canada)
(Pictograms)
Beclomethasone
ADR (Europe)
(Pictograms)
Protective Equipment
Gloves.
Lab coat.
Dust respirator. Be sure to use an
approved/certified respirator or
equivalent.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

适应症

用于治疗湿疹、过敏性皮炎、神经性皮炎、扁平苔藓、盘状红斑狼疮、掌跖脓疱病、接触性皮炎、局限性银屑病及皮肤瘙痒症等。丙酸倍氯米松气雾剂还可用于慢性或过敏性哮喘以及过敏性鼻炎。

生物活性

Beclometasone（倍氯美松）是一种糖皮质激素受体激动剂。

靶点

Glucocorticoid Receptor

体外研究

4小时后给予25 μM倍氯美松可抑制正常生理中性粒细胞的迁移和伤口引起的炎症所导向的中性粒细胞趋化作用。在胚胎植入前4小时孵育于25 μM倍氯美松中的肿瘤细胞浸润和微转移也减少。此外，赖氨氧化酶抑制剂β-氨基丙酮腈（βAPN）显著减少了胶原纤维并增强了CHT-TF诱导的中性粒细胞迁移，导致肿瘤细胞侵袭增加及随后形成微转移灶。值得注意的是，βAPN 抑制炎症引起的中性粒细胞趋化作用，表明在βAPN处理的胚胎中，肿瘤细胞侵袭增加与非病理性的中性粒细胞迁移增强相关联，而非与炎症相关。

化学性质

结晶化合物，熔点为198℃。

用途

用于制取倍氯米松二丙酸酯。

生产方法

由地塞米松制得。

反应信息

• 作为反应物：
  描述：

  倍氯米松 在 sodium carbonate 、 对甲苯磺酸 、 氯甲酸苯酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 9α-chloro-11β-hydroxy-16-methyl-21-propanoyloxypregna-1,4,6-triene-3,20-dione
  参考文献：
  名称：

  A new efficient method for conversion of corticosteroid 17.ALPHA.,21-cyclic ortho esters to 17.ALPHA.-acyloxy-21-chloro-21-deoxy derivatives.

  摘要：

  皮质激素17α，21-环状正酯（2）与各种氯甲酸酯（3）反应，以良好的收率生成了相应的17α-酰氧基-21-氯-21-去氧衍生物（4）。研究发现，几种新的衍生物，即17α-酰氧基-21-氯-11β-羟基-6α-甲基-1，4-孕甾二烯-3，20-二酮（4a-g），具有强效的血管收缩活性。

  DOI：

  10.1248/cpb.31.12
• 作为产物：
  描述：

  丙酸倍氯米松 在 potassium hydrogencarbonate 作用下， 以 甲醇 为溶剂， 反应 72.0h， 生成 倍氯米松
  参考文献：
  名称：

  Efficient Interfacially Driven Vehiculization of Corticosteroids by Pulmonary Surfactant

  摘要：

  Pulmonary surfactant is a crucial system to stabilize the respiratory air liquid interface. Furthermore, pulmonary surfactant has been proposed as an effective method for targeting drugs to the lungs. However, few studies have examined in detail the mechanisms of incorporation of drugs into surfactant, the impact of the presence of drugs on pulmonary surfactant performance at the interface under physiologically meaningful conditions, or the ability of pulmonary surfactant to use the air liquid interface to vehiculise drugs to long distances. This study focuses on the ability of pulmonary surfactant to interfacially vehiculize corticosteroids such as beclomethasone dipropionate (BDP) or Budesonide (BUD) as model drugs. The main objectives have been to (a) characterize the incorporation of corticosteroids into natural and synthetic surfactants,. (b) evaluate whether the presence of corticosteroids affects surfactant functionality, and (c) determine whether surfactant preparations enable the efficient spreading and distribution of BDP and BUD along the air liquid interface. We have compared the performance of a purified surfactant from porcine lungs and two clinical surfactants: Poractant alfa, a natural surfactant of animal origin extensively used to treat premature babies, and CHF5633, a new synthetic surfactant preparation currently under clinical trials. Both, natural and clinical surfactants spontaneously incorporated corticosteroids up to at least 10% by mass with respect to phospholipid content. The presence of the drugs did not interfere with their ability.to efficiently adsorb into air liquid interfaces and form surface active films able to reach and sustain very low surface tensions (<2 mN/m) under compression expansion cycling mimicking breathing dynamics. Furthermore, the combination of clinical surfactant with corticosteroids efficiently promoted the active diffusion of the drug to long distances along the air liquid interface. This effect could not be mimicked by vehiculisation of corticosteroids in liposomes or in micellar emulsions similar to the formulations currently in use to deliver anti-inflammatory corticosteroids through inhalation.

  DOI：

  10.1021/acs.langmuir.7b01177

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] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE TYROSINE KINASE DE BRUTON
  申请人：BIOCAD JOINT STOCK CO

  公开号：WO2018092047A1

  公开（公告）日：2018-05-24

  The present invention relates to a new compound of formula I: or pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: V1 is C or N, V2 is C(R2) or N, whereby if V1 is C then V2 is N, if V1 is C then V2 is C(R2), or if V1 is N then V2 is C(R2); each n, k is independently 0, 1; each R2, R11 is independently H, D, Hal, CN, NR'R", C(O)NR'R", C1-C6 alkoxy; R3 is H, D, hydroxy, C(O)C1-C6 alkyl, C(O)C2-C6 alkenyl, C(O)C2-C6 alkynyl, C1-C6 alkyl; R4 is H, Hal, CN, CONR'R", hydroxy, C1-C6 alkyl, C1-C6 alkoxy; L is CH2, NH, O or chemical bond; R1 is selected from the group of the fragments, comprising: Fragment 1, Fragment 2, Fragment 3 each A1, A2, A3, A4 is independently CH, N, CHal; each A5, A6, A7, A8, A9 is independently C, CH or N; R5 is H, CN, Hal, CONR'R", C1-C6 alkyl, non-substituted or substituted by one or more halogens; each R' and R" is independently selected from the group, comprising H, C1-C6 alkyl, C1-C6 cycloalkyl, aryl; R6 is selected from the group: [formula II] each R7, R8, R9, R10 is independently vinyl, methylacetylenyl; Hal is CI, Br, I, F, which have properties of inhibitor of Bruton's tyrosine kinase (Btk), to pharmaceutical compositions containing such compounds, and their use as pharmaceuticals for treatment of diseases and disorder.

  本发明涉及一种新的化合物，其化学式为I：或其药学上可接受的盐、溶剂化合物或立体异构体，其中：V1为C或N，V2为C(R2)或N，如果V1为C，则V2为N，如果V1为C，则V2为C(R2)，或者如果V1为N，则V2为C(R2)；每个n，k独立地为0或1；每个R2，R11独立地为H，D，Hal，CN，NR'R"，C(O)NR'R"，C1-C6烷氧基；R3为H，D，羟基，C(O)C1-C6烷基，C(O)C2-C6烯基，C(O)C2-C6炔基，C1-C6烷基；R4为H，Hal，CN，CONR'R"，羟基，C1-C6烷基，C1-C6烷氧基；L为CH2，NH，O或化学键；R1从包括的片段组中选择：片段1，片段2，片段3，每个A1，A2，A3，A4独立地为CH，N，CHal；每个A5，A6，A7，A8，A9独立地为C，CH或N；R5为H，CN，Hal，CONR'R"，C1-C6烷基，未取代或被一个或多个卤素取代；每个R'和R"独立地从包括H，C1-C6烷基，C1-C6环烷基，芳基的组中选择；R6从组中选择：[化学式II]每个R7，R8，R9，R10独立地为乙烯基，甲基乙炔基；Hal为CI，Br，I，F，具有布鲁顿酪氨酸激酶（Btk）抑制剂的性质，以及含有这种化合物的药物组合物，以及它们作为治疗疾病和紊乱的药物的用途。
• [EN] NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
  申请人：GALAPAGOS NV

  公开号：WO2017012647A1

  公开（公告）日：2017-01-26

  The present invention discloses compounds according to Formula (I), wherein R1, R3, R4, R5, L1, and Cy are as defined herein. The present invention also provides compounds, methods for the production of said compounds of the invention, pharmaceutical compositions comprising the same and their use in allergic or inflammatory conditions, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 and/or interferons. The present invention also methods for the prevention and/or treatment of the aforementioned diseases by administering a compound of the invention.

  本发明公开了根据式（I）的化合物，其中R1、R3、R4、R5、L1和Cy如本文所定义。本发明还提供了该发明的化合物、制备该化合物的方法、包括相同化合物的药物组合物以及它们在过敏或炎症症状、自身免疫疾病、增殖性疾病、移植排斥、涉及软骨周转障碍的疾病、先天软骨畸形和/或与IL6和/或干扰素过度分泌相关的疾病中的使用。本发明还提供了通过给予该发明的化合物来预防和/或治疗上述疾病的方法。
• [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。