扎达维林 | 101975-10-4

• 物质功能分类: 原料药 - 呼吸系统用药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 扎达维林
• 中文别名: 6-[4-(二氟甲氧基)-3-甲氧基苯基]-3(2H)-吡哒嗪酮；查达外林
• 英文名称: zardaverine
• 英文别名: 6-(4-difluoromethoxy-3-methoxyphenyl)-3(2H)pyridazinone；3-[4-(difluoromethoxy)-3-methoxyphenyl]-1H-pyridazin-6-one
• CAS: 101975-10-4
• 化学式: C₁₂H₁₀F₂N₂O₃
• mdl: MFCD00867059
• 分子量: 268.22
• InChiKey: HJMQDJPMQIHLPB-UHFFFAOYSA-N

物化性质

• 密度：
  1.38±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO：100 mg/mL（372.83 mM；需要超声）

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  59.9
• 氢给体数：
  1
• 氢受体数：
  6

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : Zardaverine
CAS-No. : 101975-10-4
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
Not a hazardous substance or mixture according to Regulation (EC) No. 1272/2008.
This substance is not classified as dangerous according to Directive 67/548/EEC.
Label elements
The product does not need to be labelled in accordance with EC directives or respective national laws.
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Synonyms : 6-(4-Difluoromethoxy-3-methoxyphenyl)-3(2H)-pyridazinone
Formula : C12H10F2N2O3
Molecular Weight : 268,22 g/mol

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Section 4. FIRST AID MEASURES
Description of first aid measures
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration.
In case of skin contact
Wash off with soap and plenty of water.
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.
Most important symptoms and effects, both acute and delayed
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. 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
Avoid dust formation. Avoid breathing vapors, mist or gas.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
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
Provide appropriate exhaust ventilation at places where dust is formed.Normal measures for preventive fire
protection.
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
General industrial hygiene practice.
Personal protective equipment
Eye/face protection
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
Choose body protection in relation to its type, to the concentration and amount of dangerous
substances, and to the specific work-place., The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
Respiratory protection is not required. Where protection from nuisance levels of dusts are desired,
use type N95 (US) or type P1 (EN 143) dust masks. 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
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
no data available
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
no data available
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 May be 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
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.
Additional Information
RTECS: Not available

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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.
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

扎达维林是一种磷酸二酯酶3A (PDE3A) 调节剂，其IUPAC名称为3-[4-(二氟甲氧基)-3-甲氧基苯基]-1H-哒嗪-6-酮。

扎达维林是哒嗪酮衍生物，作为一种磷酸二酯酶抑制剂，它对PDE3和4具有选择性。该药物可用作抗哮喘药和支气管扩张药。

作为一种新型的PDE3和4抑制剂，扎达维林的IC50分别为0.5 uM和0.8 uM。

反应信息

• 作为反应物：
  描述：

  西潘茶碱 、 5-[4-甲氧基-3-[(2S)-降冰片烷-2-基]氧基-苯基]-1,3-二嗪农-2-酮 、 茶碱 、 3-异丁基-1-甲基黄嘌呤 、 (R)-中位丙基am 、 扎达维林 、 长春西汀 、 咯利普兰 、 阿罗茶碱 、 罗氟司特 、 普马芬群 生成 多索茶碱
  参考文献：
  名称：

  Methods of treating psychiatric conditions comprising administration of muscarinic agents in combination with SSRIs

  摘要：

  该即时披露描述了通过刺激或增加神经元生成来治疗中枢神经系统和外周神经系统的疾病和状况的方法。该披露包括基于毒蕈碱受体调节的组合物和方法，例如通过抑制乙酰胆碱酯酶（AChE）活性，单独或与另一种神经生成剂结合，以刺激或促进新神经细胞的形成。

  公开号：

  US07678363B2
• 作为产物：
  描述：

  香草乙酮 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 1-(4-(difluoromethoxy)-3-methoxyphenyl)ethan-1-one 、 扎达维林
  参考文献：
  名称：

  6-(polyfluoroalkoxyphenyl) pyridazinones, their compositions, synthesis

  摘要：

  式I中，6-芳基-3-[2H]吡啶嗪酮 ##STR1## 其中R1和R2中的一个表示氢或（C1-C4）-烷氧基，另一个表示多氟（C1-C4）-烷氧基，其药理学耐受盐适用于支气管痉挛和心脏强效化合物。指出其制备过程和适当的药物。

  公开号：

  US04665074A1

文献信息

• [EN] PYRROLOTRIAZINONE DERIVATIVES AS PI3K INHIBITORS<br/>[FR] DÉRIVÉS DE PYRROLOTRIAZINONE EN TANT QU'INHIBITEURS DES PI3K
  申请人：ALMIRALL SA

  公开号：WO2014060432A1

  公开（公告）日：2014-04-24

  New pyrrolotriazinone derivatives having the chemical structure of formula (I), are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Phosphoinositide 3-Kinases (PI3Ks)

  新的吡咯三唑酮衍生物具有化学结构式（I），公开；以及它们的制备方法，包括它们的药物组合物和它们作为磷脂酰肌醇3-激酶（PI3Ks）抑制剂在治疗中的应用。
• New CRTh2 antagonists
  申请人：Almirall, S.A.

  公开号：EP2548876A1

  公开（公告）日：2013-01-23

  The present invention relates to compounds of formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by CRTh2 antagonist activity.

  本发明涉及式(I)的化合物，制备这种化合物的方法以及它们在治疗病理状况或疾病中的应用，该病理状况或疾病容易通过CRTh2拮抗活性得到改善。
• [EN] COMPOUNDS, COMPOSITIONS AND METHODS FOR CANCER PATIENT STRATIFICATION AND CANCER TREATMENT<br/>[FR] COMPOSÉS, COMPOSITIONS ET MÉTHODES POUR LA STRATIFICATION DE PATIENTS CANCÉREUX ET LE TRAITEMENT D'UN CANCER
  申请人：BAYER PHARMA AG

  公开号：WO2017134231A1

  公开（公告）日：2017-08-10

  The present invention features improved Compounds, especially (I) methods of identifying patients having Cancer using biomarkers (e.g., PDE3A, SLFN12 and/or CREB3Ll) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention (e.g., Compounds 1-6 disclosed herein).

  本发明的特点是改进的化合物，特别是（I）利用与药物敏感性相关的生物标志物（例如PDE3A、SLFN12和/或CREB3Ll）来识别患有癌症的患者的方法，并因此使用本发明的药剂（例如本文披露的化合物1-6）治疗分层患者人群。
• [EN] COMPOUNDS, COMPOSITIONS AND METHODS FOR CANCER TREATMENT<br/>[FR] COMPOSÉS, COMPOSITIONS ET MÉTHODES DE TRAITEMENT DU CANCER
  申请人：BROAD INST INC

  公开号：WO2018141835A1

  公开（公告）日：2018-08-09

  The present invention features improved compounds, especially the compound having the structure (1). Compositions and methods of identifying patients having cancer using biomarkers (e.g., PDE3A, PDE3B, SLFN12 and/or CREB3L1) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention.

  本发明的特点是改进的化合物，特别是具有结构（1）的化合物。使用与药物敏感性相关的生物标志物（例如PDE3A、PDE3B、SLFN12和/或CREB3L1）来识别患有癌症的患者的组合物和方法，从而治疗分层患者人群，使用本发明的药剂。
• Pyrazole derivatives as jak inhibitors
  申请人：Almirall, S.A.

  公开号：EP2360158A1

  公开（公告）日：2011-08-24

  New pyrazole derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).

  新的吡唑衍生物具有化学结构式（I），公开了它们的制备方法，包括它们的制药组合物以及它们作为Janus激酶（JAK）抑制剂在治疗中的用途。