阿司咪唑 | 68844-77-9

• 物质功能分类: 原料药 - 抗变态反应药 - 抗组胺药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 阿司咪唑
• 中文别名: 1-[(4-氟苯基)甲基]-N-[1-[2-(4-甲氧苯基)乙基]-4-哌啶基]-1H-苯并咪唑-2-胺；1-(4-氟苄基)-2-(1-[4-甲氧基苯乙基]哌啶-4-基)氨基苯并咪唑
• 英文名称: astemizole
• 英文别名: [3H]-astemizole；1-(4-fluorobenzyl)-N-(1-(4-methoxyphenethyl)piperidin-4-yl)-1H-benzo[d]imidazol-2-amine；astemizol；astermizole；AST；1-(4-fluorophenylmethyl)-N-{1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl}-1H-benzimidazol-2-amine；1-[(4-fluorophenyl)methyl]-N-[1-[2-(4-methoxyphenyl)ethyl]piperidin-4-yl]benzimidazol-2-amine
• CAS: 68844-77-9
• 化学式: C₂₈H₃₁FN₄O
• 分子量: 458.579
• InChiKey: GXDALQBWZGODGZ-UHFFFAOYSA-N

物化性质

• 熔点：
  172.9°C
• 沸点：
  627.3±65.0 °C(Predicted)
• 密度：
  1.1587 (estimate)
• 溶解度：
  二甲基亚砜：>20mg/mL
• 物理描述：
  Solid
• 颜色/状态：
  White crystals
• 蒸汽压力：
  1.5X10-12 mm Hg at 25 °C (est)
• 分解：
  When heated to decomposition it emits toxic fumes of /hydrogen fluoride and nitrogen oxides/.
• 解离常数：
  pKa = 8.13 (tertiary cyclohexane nitrogen) (est)
• 稳定性/保质期：
  远离氧化物。

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  42.3
• 氢给体数：
  1
• 氢受体数：
  5

ADMET

代谢

几乎完全在肝脏代谢，并主要随粪便排出。

Almost completely metabolized in the liver and primarily excreted in the feces.

来源:DrugBank

代谢

口服阿司咪唑吸收良好，但会经历广泛的首过代谢，转化为O-去甲基阿司咪唑。去甲基阿司咪唑在小肠和肝脏的微囊系统中形成，这表明细胞色素P450（P450s）在阿司咪唑的首过代谢中发挥作用。然而，参与阿司咪唑O-去甲基化的人类P450s尚未被鉴定，十二个已知的药物代谢P450s的参与也被否认。在P450鉴定研究中，发现阿司咪唑O-去甲基化在小肠的活动性高于肝脏（约3倍）。这些数据提示CYP2J可能参与其中，因为属于该亚家族的P450在小肠中主要表达。...

Orally administered astemizole is well absorbed but undergoes an extensive first-pass metabolism to O-desmethylastemizole. Desmethylastemizole is formed in the human microsomal systems of the small intestine as well as the liver, which suggests the role of cytochromes P450 (P450s) in the first-pass metabolism of astemizole. Human P450s involved in the O-demethylation of astemizole have, however, not been identified, and the involvement of twelve known drug-metabolizing P450s were denied. During the course of the P450 identification study, higher activities of the astemizole O-demethylation in the rabbit small intestine than in the liver (about 3-fold) were found. These data suggest the possible involvement of CYP2J, since P450 included in this subfamily is dominantly expressed in the small intestine of rabbits. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

... 在人肝脏微粒体系统中检测到阿司咪唑的三个代谢物，即去甲基阿司咪唑（DES-AST）、6-羟基阿司咪唑（6OH-AST）和诺阿司咪唑（NOR-AST），比例为7.4:2.8:1。使用重组P450和抗体的实验表明，CYP3A4在阿司咪唑的主要代谢途径中，即DES-AST的形成中，起到了微不足道的角色，尽管CYP3A4可能介导了相对较小的代谢途径到6OH-AST和NOR-AST。重组CYP2D6催化了6OH-AST和DES-AST的形成。然而，用人肝脏微粒体的研究表明，单一P450在DES-AST形成中起到了主要作用。 ...

... Three metabolites of astemizole were detected in a /human/ liver microsomal system, i.e. desmethylastemizole (DES-AST), 6-hydroxyastemizole (6OH-AST) and norastemizole (NOR-AST) at the ratio of 7.4:2.8:1. Experiments with recombinant P450s and antibodies indicate a negligible role for CYP3A4 on the main metabolic route of astemizole, i.e. formation of DES-AST, although CYP3A4 may mediate the relatively minor metabolic routes to 6OH-AST and NOR-AST. Recombinant CYP2D6 catalyzed the formation of 6OH-AST and DES-AST. Studies with human liver microsomes, however, suggest a major role for a mono P450 in DES-AST formation. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

第二代、相对不镇静的组胺H1受体拮抗剂（H1-RA）在全球范围内广泛用于治疗过敏性鼻炎结膜炎和慢性荨麻疹的症状。关于这些药物的药代动力学和药效学的信息虽然还不完整，但现在已足够允许优化治疗。本文总结了已发表的关于这些H1-RA的药代动力学和药效学信息，并划定了需要更多数据的领域。大多数第二代H1-RA的血清浓度相对较低，通常通过放射免疫分析测量。口服给药后，2或3小时内观察到峰值浓度。由于缺乏静脉制剂，生物利用度尚未得到很好的研究。大多数H1-RA在肝脏细胞色素P450系统中代谢：特非那丁、阿司咪唑、洛拉他丁、氮卓司丁和依巴斯汀有一个或多个活性代谢物，这些代谢物在血清中的浓度高于相应的母化合物，因此可以通过高效液相色谱法测量。西替利嗪是第一代H1受体拮抗剂羟嗪的活性代谢物，在体内不再代谢到任何程度，并通过肾脏排泄消除。勒卡巴汀也主要通过排泄消除。血清消除半衰期值在不同的一代H1-RA之间差异很大，特非那丁、阿司咪唑、洛拉他丁、西替利嗪、氮卓司丁和依巴斯汀及其活性代谢物的半衰期为24小时或更短，氮卓司丁的活性代谢物（去甲基氮卓司丁）的血清消除半衰期值约为2天，而阿司咪唑的活性代谢物（去甲基阿司咪唑）的值为9.5天。从少数发表的研究中，计算出第二代H1-RA的表观分布体积，似乎组织分布广泛。在儿童中，H1-RA的半衰期通常比成人短；没有关于阿司咪唑、洛拉他丁、氮卓司丁或依巴斯汀在儿童中药代动力学的已发表信息。在一些老年成人中，特非那丁、洛拉他丁和西替利嗪的半衰期可能比年轻健康成人长。关于第二代H1-RA在肝功能受损患者中药代动力学的已发表数据很少。西替利嗪的半衰期在肾功能受损者中延长。关于H1-RA在新生儿、妊娠或哺乳期间药代动力学的信息非常缺乏。

Second-generation, relatively nonsedating histamine H1-receptor antagonists (H1-RA) are extensively used worldwide for the symptomatic treatment of allergic rhinoconjunctivitis and chronic urticaria. Information about the pharmacokinetics and pharmacodynamics of these medications, while still incomplete, is now sufficient to permit optimisation of therapy. Published pharmacokinetic and pharmacodynamic information on these H1-RA is summarised here, and areas where more data are required are delineated. Serum concentrations of most second-generation H1-RA are relatively low, and are usually measured by radioimmunoassay. After oral administration, peak concentrations are observed within 2 or 3 h. Bioavailability has not been well studied, due to the lack of intravenous formulations. Most H1-RA are metabolised in the hepatic cytochrome P450 system: terfenadine, astemizole, loratadine, azelastine, and ebastine have 1 or more active metabolites which are present in serum in higher concentrations than the respective parent compound, and therefore can be measured by high performance liquid chromatography. Cetirizine, an active metabolite of the first generation H1-receptor antagonist hydroxyzine, is not further metabolised to any great extent in vivo, and is eliminated via renal excretion. Levocabastine is also eliminated primarily by excretion. Serum elimination half-life values differ greatly from 1 H1-RA to another, and are 24 h or less for terfenadine, astemizole, loratadine, cetirizine, azelastine and ebastine, and the active metabolites of terfenadine, loratadine and ebastine. The active metabolite of azelastine (demethylazelastine) has a serum elimination half-life value of about 2 days, while that of astemizole (demethyl-astemizole) has a value of 9.5 days. From the few published studies in which the apparent volumes of distribution of the second-generation H1-RA have been calculated, it appears that tissue distribution is extensive. In children, the half-lives of H1-RA are generally shorter than are found in adults; there is no published information on the pharmacokinetics of astemizole, loratadine, azelastine, or ebastine in children. In some elderly adults, terfenadine, loratadine and cetirizine may have longer half-lives than in young healthy adults. There is little published data on the pharmacokinetics of the second-generation H1-RA in patients with impaired hepatic function. The half-life of cetirizine is prolonged in those with impaired renal function. There is a paucity of information on the pharmacokinetics of H1-RA in neonates, in pregnancy or during lactation.

来源:Hazardous Substances Data Bank (HSDB)

代谢

阿司咪唑及其代谢物在大鼠和小鼠中的抗过敏作用被研究。所有测试的阿司咪唑代谢物在抑制小鼠回肠收缩和组胺诱导的支气管收缩方面都比原化合物更活跃。去甲基阿司咪唑在抑制小鼠小脑中的美吡拉明结合方面与阿司咪唑大致相同。在异源性被动皮肤过敏反应（PCA）和同源性PCA中，代谢物引起的几乎与阿司咪唑相同的等效抑制。阿司咪唑或去甲基阿司咪唑没有观察到H2-拮抗活性。

The antiallergic effects of astemizole and its metabolites were studied in rats and guinea pigs. All of the metabolites of astemizole tested were more active than the parent compound in inhibiting contraction of the ileum and bronchoconstriction induced by histamine in guinea pigs. Desmethylastemizole was about the same as astemizole in inhibiting mepyramine binding in guinea pig cerebellum. In heterologous passive cutaneous anaphylaxis (PCA) and homologous PCA, the metabolites caused almost equipotent inhibition to that seen with astemizole. No H2-antagonistic activity was seen with astemizole or desmethylastemizole.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

阿司咪唑与组胺竞争在胃肠道、子宫、大血管和支气管肌肉中的H1受体结合位点。这种可逆的结合抑制了由组胺活动引起的肿胀、红斑和瘙痒的形成。由于该药物不易穿过血脑屏障，并且优先在与大脑周围而不是内部的H1受体上结合，因此对中枢神经系统的影响最小。阿司咪唑还可能作用于H3受体，产生不良反应。

Astemizole competes with histamine for binding at H₁-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle. This reversible binding of astemizole to H₁-receptors suppresses the formation of edema, flare, and pruritus resulting from histaminic activity. As the drug does not readily cross the blood-brain barrier and preferentially binds at H1 receptors in the peripehery rather than within the brain, CNS depression is minimal. Astemizole may also act on H₃-receptors, producing adverse effects.

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

心血管不良事件。在某些情况下，严重心律失常的识别之前有晕厥发作。同样，也有罕见报道使用阿司咪唑出现低血压、心悸和眩晕的情况，这可能反映了未检测到的室性心律失常。(L1864)

Cardiovascular adverse events. In some cases, recognition of severe arrhythmias has been preceded by episodes of syncope. Similarly, rare cases of hypotension, palpitations, and dizziness have also been reported with Astemizole use, which may reflect undetected ventricular arrhythmia. (L1864)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口腔。从胃肠道快速吸收。

Oral. Rapidly absorbed from the gastrointestinal tract.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性数据

LD50：2052毫克/千克（小鼠）（A308）

LD50: 2052mg/kg (Mouse) (A308)

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

• 吸收

从胃肠道迅速吸收。

Rapidly absorbed from the gastrointestinal tract.

来源:DrugBank

吸收、分配和排泄

蛋白质结合率：96%

Protein binding: 96%

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

达峰时间：1小时内。

Time to peak concentration: Within 1 hour.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

尚不清楚阿司咪唑是否分布到人乳中。阿司咪唑会分布到狗的乳汁中。

It is not known whether astemizole is distributed into human breast milk. Astemizole is distributed into the milk of dogs.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在随餐服用阿司咪唑后，该药物的口服生物利用度降低了60%。

Following concomitant administration of astemizole with food, oral bioavailability of the drug is decreased by 60%.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S26,S36
• 危险类别码：
  R22,R36/37/38
• WGK Germany：
  3
• 海关编码：
  2933990090
• RTECS号：
  DD8968000
• 储存条件：
  存放在密封容器中，并放置在阴凉、干燥处。储存地点须远离氧化剂。

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : Astemizole
CAS-No. : 68844-77-9
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

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Section 2. HAZARDS IDENTIFICATION
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008 [EU-GHS/CLP]
Skin irritation (Category 2)
Eye irritation (Category 2)
Specific target organ toxicity - single exposure (Category 3)
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Harmful if swallowed. Irritating to eyes, respiratory system and skin.
Label elements
Labelling according Regulation (EC) No 1272/2008 [CLP]
Pictogram
Signal word Warning
Hazard statement(s)
H315 Causes skin irritation.
H319 Causes serious eye irritation.
H335 May cause respiratory irritation.
Precautionary statement(s)
P261 Avoid breathing dust/ fume/ gas/ mist/ vapours/ spray.
P305 + P351 + P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove
contact lenses, if present and easy to do. Continue rinsing.
Supplemental Hazard none
Statements
According to European Directive 67/548/EEC as amended.
Hazard symbol(s)
R-phrase(s)
R22 Harmful if swallowed.
R36/37/38 Irritating to eyes, respiratory system and skin.
S-phrase(s)
S26 In case of contact with eyes, rinse immediately with plenty of water and
seek medical advice.
S36 Wear suitable protective clothing.
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Formula : C28H31FN4O
Molecular Weight : 458,57 g/mol
Component Concentration
Astemizole
CAS-No. 68844-77-9 -
EC-No. 272-441-9

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Section 4. FIRST AID MEASURES
Description of first aid measures
General advice
Consult a physician. Show this safety data sheet to the doctor in attendance.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Consult a physician.
In case of eye contact
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.
Most important symptoms and effects, both acute and delayed
Indication of any immediate medical attention and special treatment needed
no data available

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Section 5. FIREFIGHTING MEASURES
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, nitrogen oxides (NOx), Hydrogen fluoride
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

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Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure
adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed
containers for disposal.
Reference to other sections
For disposal see section 13.

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Section 7. HANDLING AND STORAGE
Precautions for safe handling
Avoid contact with skin and eyes. Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Recommended storage temperature: 2 - 8 °C
Store with desiccant. Light sensitive.
Specific end uses
no data available

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Section 8. EXPOSURE CONTROLS/PERSONAL PROTECTION
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and
at the end of workday.
Personal protective equipment
Eye/face protection
Safety glasses with side-shields conforming to EN166 Use equipment for eye protection tested
and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique
(without touching glove's outer surface) to avoid skin contact with this product. Dispose of
contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and
the standard EN 374 derived from it.
Body Protection
impervious clothing, The type of protective equipment must be selected according to the
concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher
level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges.
Use respirators and components tested and approved under appropriate government standards
such as NIOSH (US) or CEN (EU).

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Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Information on basic physical and chemical properties
a) Appearance Form: solid
b) Odour no data available
c) Odour Threshold no data available
d) pH no data available
e) Melting point/freezing no data available
point
f) Initial boiling point and no data available
boiling range
g) Flash point no data available
h) Evaporation rate no data available
i) Flammability (solid, gas) no data available
j) Upper/lower no data available
flammability or
explosive limits
k) Vapour pressure no data available
l) Vapour density no data available
m) Relative density no data available
n) Water solubility no data available
o) Partition coefficient: n- no data available
octanol/water
p) Autoignition no data available
temperature
q) Decomposition no data available
temperature
r) Viscosity no data available
s) Explosive properties no data available
t) Oxidizing properties no data available
Other safety information
no data available

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Section 10. STABILITY AND REACTIVITY
Reactivity
no data available
Chemical stability
no data available
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
no data available
Hazardous decomposition products
Other decomposition products - no data available

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Section 11. TOXICOLOGICAL INFORMATION
Information on toxicological effects
Acute toxicity
LD50 Oral - rat - > 2.560 mg/kg
Inhalation: Irritating to respiratory system.
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitization
no data available
Germ cell mutagenicity
no data available
Carcinogenicity
IARC: No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
Reproductive toxicity - rat - Subcutaneous
Effects on Newborn: Growth statistics (e.g., reduced weight gain). Effects on Newborn: Behavioral. Effects
on Newborn: Physical.
Specific target organ toxicity - single exposure
Inhalation - May cause respiratory irritation.
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Potential health effects
Inhalation May be harmful if inhaled. Causes respiratory tract irritation.
Ingestion May be harmful if swallowed.
Skin May be harmful if absorbed through skin. Causes skin irritation.
Eyes Causes serious eye irritation.
Additional Information
RTECS: DD8968000

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Section 12. ECOLOGICAL INFORMATION
Toxicity
no data available
Persistence and degradability
no data available
Bioaccumulative potential
no data available
Mobility in soil
no data available
Results of PBT and vPvB assessment
no data available
Other adverse effects
no data available

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Section 13. DISPOSAL CONSIDERATIONS
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company. Dissolve or mix the material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.
Contaminated packaging
Dispose of as unused product.

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Section 14. TRANSPORT INFORMATION
UN number
ADR/RID: - IMDG: - IATA: -
UN proper shipping name
ADR/RID: Not dangerous goods
IMDG: Not dangerous goods
IATA: Not dangerous goods
Transport hazard class(es)
ADR/RID: - IMDG: - IATA: -
Packaging group
ADR/RID: - IMDG: - IATA: -
Environmental hazards
ADR/RID: no IMDG Marine pollutant: no IATA: no
Special precautions for user
no data available

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Section 15. REGULATORY INFORMATION
This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006.
Safety, health and environmental regulations/legislation specific for the substance or mixture
no data available
Chemical Safety Assessment
no data available

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Section 16. OTHER INFORMATION
Further information
Copyright 2012 Co. LLC. License granted to make unlimited paper copies for internal use
only.
The above information is believed to be correct but does not purport to be all inclusive and shall be
used only as a guide. The information in this document is based on the present state of our knowledge
and is applicable to the product with regard to appropriate safety precautions. It does not represent any
guarantee of the properties of the product. Corporation and its Affiliates shall not be held
liable for any damage resulting from handling or from contact with the above product. See
and/or the reverse side of invoice or packing slip for additional terms and conditions of sale.

制备方法与用途

生物活性

Astemizole (R 43512) 是一种组胺 H1 受体拮抗剂，其 IC50 值为 4.7 nM。它还是一种有效的 ether à-go-go 1 (Eag1) 和 Eag 相关基因 (Erg) 钾通道抑制剂，并具有抗肿瘤和止痒作用。

靶点

Target	Value
Eag1
Erg potassium channel
H1 receptor	Cell-free assay

化学性质

Astemizole 是一种无臭的白色结晶，熔点为 149.1℃。它易溶于有机溶剂，几乎不溶于水。其紫外吸收峰在乙醇中的最大值分别为 219、249 和 286 nm（ε27：250．229，ε578：8634．280），盐酸溶液中为 209 和 277 nm（ε578：18073．394）。急性毒性实验表明，Astemizole 口服大鼠 LD50 值大于 2560 mg/kg。

用途

Astemizole 是一种新型 H1 组胺受体拮抗剂，具有较强的结合力和较长的持续时间。适用于慢性荨麻疹、枯草热、季节性过敏性鼻炎、过敏性结膜炎及过敏性哮喘等疾病的治疗。

生产方法

化合物 (I) 和碘甲烷在乙醇中回流 8 小时，环合得到化合物 (Ⅱ)，再通过水解脱去酯基获得化合物 (Ⅲ)。之后用对甲氧基苯乙基溴进行 N-烷基化，制得化合物 (IV)；再使用对氟苄基溴烷基化，最终合成阿司咪唑。

分类

有毒物品

毒性分级

中毒

急性毒性

口服 - 大鼠 LD50: >2560 mg/kg; 口服 - 小鼠 LD50: 2560 mg/kg

燃烧特性

可燃；燃烧时会产生有毒氮氧化物和氟化物烟雾

人用药副作用

心律失常、昏迷、恶心、呕吐及嗜睡等

储运特性

通风低温干燥，避免与食品原料混存

灭火剂

干粉、泡沫、沙土、二氧化碳或雾状水

反应信息

• 作为反应物：
  描述：

  阿司咪唑 在 水 、 氢溴酸 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 14.0h， 生成 1-(4-fluorobenzyl)-N-(1-(4-(2-fluorobutoxy)phenethyl)piperidin-4-yl)-1H-benzo[d]imidazol-2-amine
  参考文献：
  名称：

  Radiosynthesis and characterization of astemizole derivatives as lead compounds toward PET imaging of τ-pathology

  摘要：

  由微管相关 tau 蛋白组成的神经纤维缠结是包括阿尔茨海默病在内的一系列神经退行性疾病的标志。因此，神经纤维缠结的体内成像是目前正电子发射断层扫描研究的重点。本文报告了利用合成聚集体作为神经纤维缠结模型的体外放射性配体结合试验的开发情况，以及对 tau 蛋白配体 astemizole 新型衍生物的评估。

  DOI：

  10.1039/c3md00017f
• 作为产物：
  描述：

  4-(2-(4-((1-((4-氟苯基)甲基)-1H-苯并咪唑-2-基)氨基)-1-哌啶基)乙基)-苯酚 在 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.42h， 生成 阿司咪唑
  参考文献：
  名称：

  Cardiovascular safety assay

  摘要：

  本发明提供了用于筛选试验化合物在受试者中引起心脏毒性能力的测定和试剂盒。所述测定和试剂盒基于这样的发现：利用astemizole与HERG钾通道的相互作用，可以在新药物和其他药物代理的开发过程中预测化合物的心脏毒性。

  公开号：

  US20070166229A1

文献信息

• Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20150231142A1

  公开（公告）日：2015-08-20

  The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.

  本发明涉及含有上皮钠通道活性抑制剂与至少一种ABC转运蛋白调节剂化合物（A式、B式、C式或D式）的药物组合物。该发明还涉及这些药物配方，以及使用这些组合物治疗CFTR介导的疾病，特别是囊性纤维化的方法。
• 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。
• SULFOXIMINE SUBSTITUTED QUINAZOLINES FOR PHARMACEUTICAL COMPOSITIONS
  申请人：BLUM Andreas

  公开号：US20140135309A1

  公开（公告）日：2014-05-15

  This invention relates to novel sulfoximine substituted quinazoline derivatives of formula I wherein Ar, R 1 and R 2 are as defined herein, and their use as MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.

  这项发明涉及公式I的新型磺酰胺取代的喹唑啉衍生物，其中Ar、R1和R2如本文所定义，并且它们作为MNK1（MNK1a或MNK1b）和/或MNK2（MNK2a或MNK2b）激酶抑制剂的用途，含有这些化合物的药物组合物，以及将其用作治疗或改善MNK1（MNK1a或MNK1b）和/或MNK2（MNK2a或MNK2b）介导的疾病的药剂的方法。
• [EN] SULFOXIMINE SUBSTITUTED QUINAZOLINES FOR PHARMACEUTICAL COMPOSITIONS<br/>[FR] QUINAZOLINES SUBSTITUÉES PAR SULFOXIMINE POUR COMPOSITIONS PHARMACEUTIQUES
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2014072244A1

  公开（公告）日：2014-05-15

  This invention relates to novel sulfoximine substituted quinazoline derivatives of formula (I), wherein Ar, R1 and R2 are as defined in the description and claims, and their use as MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.

  这项发明涉及一种新型的配方(I)的磺酰胺取代喹唑啉衍生物，其中Ar、R1和R2如描述和声明中所定义，并且它们作为MNK1（MNK1a或MNK1b）和/或MNK2（MNK2a或MNK2b）激酶抑制剂的用途，含有这些化合物的药物组合物，以及将其用作治疗或改善MNK1（MNK1a或MNK1b）和/或MNK2（MNK2a或MNK2b）介导的疾病的药剂的方法。