苯噻啶 | 15574-96-6

• 物质功能分类: 原料药 - 解热镇痛药 - 抗偏头痛药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 环七噻吩
• 中文名称: 苯噻啶
• 中文别名: 新度美安；4-(9,10-二氢-4H-苯并[4,5]环庚烷并[1,2-b]噻吩-4-亚基)-1-甲基哌啶
• 英文名称: pizotifen
• 英文别名: 4-(9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-yliden)-1-methyl-piperidine；pizotyline；CPD000466272；NSC291564；4-(9,10-dihydro-benzo[4,5]cyclohepta[1,2-b]thiophen-4-ylidene)-1-methyl-piperidine；1-methyl-4-(6-thiatricyclo[8.4.0.03,7]tetradeca-1(14),3(7),4,10,12-pentaen-2-ylidene)piperidine
• CAS: 15574-96-6
• 化学式: C₁₉H₂₁NS
• mdl: MFCD00864192
• 分子量: 295.448
• InChiKey: FIADGNVRKBPQEU-UHFFFAOYSA-N

物化性质

• 熔点：
  140-142°C
• 沸点：
  436.7±45.0 °C(Predicted)
• 密度：
  1.164±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：≥8mg/mL
• 碰撞截面：
  175.4 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]
• 保留指数：
  2367;2412;2358.3;2375;2375

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.368
• 拓扑面积：
  31.5
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

匹佐替芬在肝脏中被广泛代谢，它主要通过N-葡萄糖醛酸化反应形成主要代谢物，即N-葡萄糖醛酸苷。N-葡萄糖醛酸苷占血浆中至少50%，以及尿液中60-70%的放射性排泄物。

Pizotifen is extensively metabolized in the liver, where it primarily undergoes N-glucuronidation to form the main metabolite, N-glucuronide conjugate. N-glucuronide conjugate accounts for at least 50% of the plasma and 60-70% of the urinary-excreted radioactivity.

来源:DrugBank

毒理性

• 蛋白质结合

吡唑他芬的血浆蛋白结合率大于90%。

Plasma protein binding of pizotifen is > 90%.

来源:DrugBank

吸收、分配和排泄

• 吸收

吡唑坦经口服给药后的吸收半衰期在成年男性中为0.5至0.8小时，几乎完全吸收率为80%。最大血药浓度在给药后5小时达到，绝对生物利用度为78%。

The absorption half-life of pizotifen following oral administration is 0.5 to 0.8 hours in an adult male with nearly complete absorption rate of 80%. Maximum blood levels are reached 5 hours post-administration and the absolute bioavailability is 78%.

来源:DrugBank

吸收、分配和排泄

• 消除途径

大约三分之一的口服总剂量会排入粪便中。不到1%的总剂量会以未改变的母药形式通过尿液排出，多达55%的剂量会以代谢物的形式排出。

About one third of the total orally administered dose is excreted into the feces. Less than 1% of the total dose is excreted in the urine as the unchanged parent drug, and up to 55% of the dose is excreted as its metabolites.

来源:DrugBank

吸收、分配和排泄

• 分布容积

一个成年男性的分布体积为833L用于匹莫亭，70L用于N-葡萄糖醛酸苷。

The volume of distribution in an adult male is 833L for pizotifen and 70L for the N-glucuronide conjugate.

来源:DrugBank

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S37/39
• 危险类别码：
  R22,R36/37/38,R63
• WGK Germany：
  3
• RTECS号：
  TM7165000
• 危险性防范说明：
  P201,P202,P264,P270,P280,P301+P312+P330,P308+P313,P405,P501
• 危险性描述：
  H302,H361
• 储存条件：
  Refrigerator

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : Pizotifen
CAS-No. : 15574-96-6
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]
Acute toxicity, Oral (Category 4)
Reproductive toxicity (Category 2)
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Harmful if swallowed. Possible risk of harm to the unborn child.
Label elements
Labelling according Regulation (EC) No 1272/2008 [CLP]
Pictogram
Signal word Warning
Hazard statement(s)
H302 Harmful if swallowed.
H361 Suspected of damaging fertility or the unborn child.
Precautionary statement(s)
P281 Use personal protective equipment as required.
Supplemental Hazard none
Statements
According to European Directive 67/548/EEC as amended.
Hazard symbol(s)
R-phrase(s)
R22 Harmful if swallowed.
R63 Possible risk of harm to the unborn child.
S-phrase(s)
S36/37 Wear suitable protective clothing and gloves.
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Formula : C19H21NS
Molecular Weight : 295,44 g/mol
Component Concentration
PIZOTIFEN
CAS-No. 15574-96-6 -
EC-No. 239-632-9

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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
Flush eyes with water as a precaution.
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
Nausea, Headache, Dizziness, Drowsiness, dry mouth, To the best of our knowledge, the chemical, physical,
and toxicological properties have not been thoroughly investigated.
Indication of any immediate medical attention and special treatment needed
no data available

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Section 5. FIRE-FIGHTING 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
no data available
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
Prevent further leakage or spillage if safe to do so. 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.
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
Complete suit protecting against chemicals, The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
Where risk assessment shows air-purifying respirators are appropriate use a full-face particle
respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering
controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. 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- log Pow: 3,803
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
Strong oxidizing agents
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 - 410 mg/kg
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
Suspected human reproductive toxicant
Specific target organ toxicity - single exposure
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Potential health effects
Inhalation May be harmful if inhaled. May cause respiratory tract irritation.
Ingestion Harmful if swallowed.
Skin May be harmful if absorbed through skin. May cause skin irritation.
Eyes May cause eye irritation.
Signs and Symptoms of Exposure
Nausea, Headache, Dizziness, Drowsiness, dry mouth, To the best of our knowledge, the chemical, physical,
and toxicological properties have not been thoroughly investigated.
Additional Information
RTECS: TM7165000

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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
N/A

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

抗组胺药物：苯噻啶

概述 苯噻啶又称新度美安、苹果酸苯噻啶，是一种化学合成的抗组胺药。其结构类似塞庚啶和阿米替林，具有强烈的抗5-羟色胺及抗组胺作用，并具备较弱的抗乙酰胆碱作用。它常用于预防偏头痛，此外还具有镇痛、镇静与抗抑郁等多重功效。苯噻啶可降低对酒精的耐受性，增加安定剂和镇静剂的作用效果。

适应症

1. 典型与非典型性偏头痛：能够减轻症状、减少发作频率及持续时间。
2. 红斑性肢痛症、血管神经性水肿、慢性荨麻疹及皮肤划痕症。
3. 类癌综合征引起的腹泻和面部潮红、颈动脉痛及真性红细胞增多导致的瘙痒等。

用法用量

• 片剂：0.5mg/片
• 成人剂量为每次0.5～1mg，每日1～3次。
• 起始阶段（第1～3天），每晚0.5mg；随后调整至每日午、晚餐后各0.5mg；自第七日起早晚及午间服用0.5mg。
• 根据个体情况逐步减少剂量：每周递减0.5mg，直至适当维持量。
• 一般建议服药两周后观察效果。多数患者服用时间为4～6个月，停药3～4周后再评估使用。

理化性质

• 类白色针状结晶，无味。
• 熔点为147.5—151.5℃。
• 可溶于乙醇、氯仿等有机溶剂或酸溶液中；不溶于水。
• 合成自2-氯甲基噻吩。

用药说明

• 长期服用：毒性较小，可安全使用。建议连续服药半年后暂停观察效果，并避免体内药物蓄积。
• 长期使用者需定期检查血象变化。
• 禁忌与注意事项：
  • 不宜与单胺氧化酶抑制剂合用。
  • 患有闭角形青光眼或前列腺肥大导致尿闭症的患者应禁用。

不良反应

1. 嗜睡与食欲增加：通常在最初使用的一至两周内出现，随着持续服药可能逐渐减轻或消失。驾驶人员、高空作业者需谨慎。
2. 其他副作用包括但不限于肌肉酸痛或痉挛、不安腿综合症、液体滞留、轻微头痛、面部潮红、性欲减退、癫痫发作加重、多梦、心悸、皮疹、月经紊乱、失眠及白细胞减少等。
3. 对青光眼、前列腺肥大患者及孕妇禁用。长期使用需关注血象变化。

用途 主要用于抗偏头痛治疗。

反应信息

• 作为反应物：
  描述：

  苯噻啶 在 sodium hydride 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 、 甲苯 、 mineral oil 为溶剂， 反应 42.5h， 生成 ethyl 4-[2-(2-ethoxycarbonylvinyl)-9,10-dihydro-1-thiabenzo[f]azulen-4-ylidene]piperidine-1-carboxylate
  参考文献：
  名称：

  PROCESS FOR PRODUCING THIABENZOAZULENE-PROPIONIC ACID DERIVATIVE

  摘要：

  本发明揭示了一种生产噻苯并噻唑蓝-丙酸衍生物的方法，该衍生物可用作抗组胺剂等药物的活性成分。根据本发明的生产方法，可以生产出噻苯并噻唑蓝-丙酸衍生物，其中噻苯并噻唑蓝骨架的2位被丙酸取代。因此，通过合成出的噻苯并噻唑蓝-丙酸衍生物具有优秀的对组胺H1受体的拮抗作用和低的颅内转移，因此可用作药物组合物的活性成分，例如抗组胺剂。

  公开号：

  US20120123127A1

文献信息

• [EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
  申请人：GILEAD APOLLO LLC

  公开号：WO2017075056A1

  公开（公告）日：2017-05-04

  The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.

  本发明提供了化合物I和II，这些化合物可用作乙酰辅酶A羧化酶（ACC）的抑制剂，以及它们的组合物和使用方法。
• [EN] QUINAZOLINE DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO<br/>[FR] DÉRIVÉS DE QUINAZOLINE, COMPOSITIONS ET UTILISATIONS ASSOCIÉES
  申请人：UNIV EMORY

  公开号：WO2013181135A1

  公开（公告）日：2013-12-05

  The disclosure relates to quinazoline derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to inhibitors of NADPH-oxidases (Nox enzymes) and/or myeloperoxidase.

  该披露涉及喹唑啉衍生物、组合物以及相关方法。在某些实施例中，该披露涉及NADPH-氧化酶（Nox酶）和/或髓过氧化物酶的抑制剂。
• TRIAZOLE ACC INHIBITORS AND USES THEREOF
  申请人：Gilead Apollo, LLC

  公开号：US20170166584A1

  公开（公告）日：2017-06-15

  The present invention provides triazole compounds useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.

  本发明提供了三唑化合物，可用作乙酰辅酶A羧化酶（ACC）的抑制剂，以及其组合物和使用方法。
• [EN] ISOTOPE ENHANCED AMBROXOL FOR LONG LASTING AUTOPHAGY INDUCTION<br/>[FR] AMBROXOL À ISOTOPE AMÉLIORÉ POUR INDUCTION D'AUTOPHAGIE DURABLE
  申请人：STC UNM

  公开号：WO2018148113A1

  公开（公告）日：2018-08-16

  The present invention is directed to 13C and/or 2H isotope enhanced ambroxol ("isotope enhanced ambroxol") and its use in the treatment of autophagy infections, especially mycobacterial and other infections, disease states and/or conditions of the lung, such as tuberculosis, especially including drug resistant and multiple drag resistant tuberculosis. Pharmaceutical compositions comprising isotope enhanced amhroxol, alone or in combination with an additional bioactive agent, especially rifamycin antibiotics, including an additional autophagy modulator (an agent which is active to promote or inhibit autophagy), thus being useful against, an autophagy mediated disease state and/or condition), especially an antophagy mediated disease state and/or condition which occurs in the lungs, for example, a Mycobacterium infection. Chronic Obstructive Pulmonary Disease (COPD), asthma, pulmonary fibrosis, cystic fibrosis, Sjogren's disease and lung cancer (small cell and non-small cell lung cancer, among other disease states and/or conditions, especially of the lung. Methods of treating autophagy disease states and/or conditions, especially including autophagy disease states or conditions which occur principally in the lungs of a patient represent a further embodiment of the present invention. An additional embodiment includes methods of synthesizing compounds according to the present invention as otherwise disclosed herein.

  本发明涉及13C和/或2H同位素增强的氨溴索（“同位素增强的氨溴索”）及其在治疗自噬感染，特别是结核分枝杆菌和其他感染、疾病状态和/或肺部疾病条件中的用途，如肺结核，特别是包括耐药和多重耐药结核病。包括同位素增强的氨溴索的药物组合物，单独或与额外的生物活性剂（特别是利福霉素类抗生素，包括额外的自噬调节剂（一种能够促进或抑制自噬的剂），因此对抗自噬介导的疾病状态和/或条件有用），特别是在肺部发生的自噬介导的疾病状态和/或条件，例如分枝杆菌感染。慢性阻塞性肺病（COPD）、哮喘、肺纤维化、囊性纤维化、干燥综合征和肺癌（小细胞和非小细胞肺癌等其他肺部疾病状态和/或条件，特别是肺部疾病状态和/或条件。治疗自噬疾病状态和/或条件的方法，特别包括治疗主要发生在患者肺部的自噬疾病状态或条件的方法，代表本发明的另一实施例。另一实施例包括根据本发明在此披露的其他方法合成化合物的方法。
• [EN] COMPOUNDS (CYSTEIN BASED LIPOPEPTIDES) AND COMPOSITIONS AS TLR2 AGONISTS USED FOR TREATING INFECTIONS, INFLAMMATIONS, RESPIRATORY DISEASES ETC.<br/>[FR] COMPOSÉS (LIPOPEPTIDES À BASE DE CYSTÉINE) ET COMPOSITIONS EN TANT QU'AGONISTES DES TLR2 UTILISÉS POUR TRAITER DES INFECTIONS, INFLAMMATIONS, MALADIES RESPIRATOIRES ENTRE AUTRES
  申请人：IRM LLC

  公开号：WO2011119759A1

  公开（公告）日：2011-09-29

  The invention provides a novel class of compounds viz. generally lipopeptides like Pam3CSK4, immunogenic compositions and pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with Toll-Like Receptors 2. In one aspect, the compounds are useful as adjuvants for enhancing the effectiveness a vaccine.

  这项发明提供了一类新型化合物，即一般类似Pam3CSK4的脂肽类化合物，包括含有这类化合物的免疫原组合物和药物组合物，以及使用这类化合物治疗或预防与Toll样受体2相关的疾病或紊乱的方法。在一个方面，这些化合物可用作增强疫苗效果的佐剂。

表征谱图