2,5-己酮可可碱 | 117570-53-3

• 物质功能分类: 生物化工 - 抑制剂 - 血管生成(Angiogenesis)
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: 2,5-己酮可可碱
• 中文别名: 5,6-二甲基吨酮-4-乙酸；5,6-二甲基-9H-氧杂蒽-9-酮-4-乙酸；5,6-二甲基-9-氧-9-氢-氧杂蒽-4-乙酸(DMXAA,ASA404)；5,6-二甲基呫吨酮-4-乙酸
• 英文名称: vadimezan
• 英文别名: DMXAA；5,6-dimethylxanthenone-4-acetic acid；5,6-dimethylxanthone-4-acetic acid；ASA404；(5,6-dimethyl-9-oxo-9H-xanthen-4-yl)acetic acid；2-(5,6-dimethyl-9-oxoxanthen-4-yl)acetic acid
• CAS: 117570-53-3
• 化学式: C₁₇H₁₄O₄
• mdl: MFCD00870555
• 分子量: 282.296
• InChiKey: XGOYIMQSIKSOBS-UHFFFAOYSA-N

物化性质

• 熔点：
  259-261 °C
• 沸点：
  520.9±50.0 °C(Predicted)
• 密度：
  1.321±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO：17 mg/mL，可溶

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.176
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

DMXAA已知的人类代谢物包括(2S,3S,4S,5R)-6-[2-(5,6-二甲基-9-氧杂蒽-4-基)乙酰基]氧基-3,4,5-三羟基氧杂环己烷-2-羧酸和6-羟基-MXAA。

DMXAA has known human metabolites that include (2S,3S,4S,5R)-6-[2-(5,6-dimethyl-9-oxoxanthen-4-yl)acetyl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid and 6-hydroxy-MXAA.

来源:NORMAN Suspect List Exchange

安全信息

• 危险品标志：
  Xn,N
• 安全说明：
  S60,S61
• 危险类别码：
  R22,R50/53
• WGK Germany：
  3
• 危险品运输编号：
  UN 3077
• RTECS号：
  ZD5536200
• 海关编码：
  2932999099
• 危险标志：
  GHS07,GHS09
• 危险性描述：
  H302,H400
• 危险性防范说明：
  P273
• 储存条件：
  2-8°C

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : DMXAA
CAS-No. : 117570-53-3
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)
Acute aquatic toxicity (Category 1)
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Harmful if swallowed. Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic
environment.
Label elements
Labelling according Regulation (EC) No 1272/2008 [CLP]
Pictogram
Signal word Warning
Hazard statement(s)
H302 Harmful if swallowed.
H400 Very toxic to aquatic life.
Precautionary statement(s)
P273 Avoid release to the environment.
Supplemental Hazard none
Statements
According to European Directive 67/548/EEC as amended.
Hazard symbol(s)
R-phrase(s)
R22 Harmful if swallowed.
R50/53 Very toxic to aquatic organisms, may cause long-term adverse effects in
the aquatic environment.
S-phrase(s)
S60 This material and its container must be disposed of as hazardous waste.
S61 Avoid release to the environment. Refer to special instructions/ Safety
data sheets.
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Synonyms : 5,6-Dimethylxanthenone-4-acetic Acid
Formula : C17H14O4 C17H14O4
Molecular Weight : 282,29 g/mol
Component Concentration
5,6-Dimethyl-9-oxo-9H-xanthene-4-acetic acid
CAS-No. 117570-53-3 -

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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
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
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. Discharge into the
environment must be avoided.
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.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.
Recommended storage temperature: 2 - 8 °C
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
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- log Pow: 3,207
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 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: ZD5536200

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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
Very toxic to aquatic life.
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. Contact a licensed
professional waste disposal service to dispose of this material. 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: 3077 IMDG: 3077 IATA: 3077
UN proper shipping name
ADR/RID: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S. (5,6-Dimethyl-9-oxo-9H-
xanthene-4-acetic acid)
IMDG: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S. (5,6-Dimethyl-9-oxo-9H-
xanthene-4-acetic acid)
IATA: Environmentally hazardous substance, solid, n.o.s. (5,6-Dimethyl-9-oxo-9H-xanthene-4-acetic
acid)
Transport hazard class(es)
ADR/RID: 9 IMDG: 9 IATA: 9
Packaging group
ADR/RID: III IMDG: III IATA: III
Environmental hazards
ADR/RID: yes IMDG Marine pollutant: yes IATA: yes
Special precautions for user
Further information
EHS-Mark required (ADR 2.2.9.1.10, IMDG code 2.10.3) for single packagings and combination
packagings containing inner packagings with Dangerous Goods > 5L for liquids or > 5kg for solids.

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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

DMXAA（Vadimezan）是一种血管破坏剂 (VDA)，同时也是DT-diaphorase的竞争性抑制剂，在无细胞试验中Ki值为20 μM，IC50值为62.5 μM。此外，DMXAA还是一种STING激动剂，具有潜在的抗肿瘤活性。

在体外实验中，DMXAA能有效诱导IFN-β和TNF-α表达，尽管对TNF-α的影响较小。它也表现出抗病毒活性，并已进入三期临床试验阶段。

靶点

目标	值
DT-diaphorase (无细胞试验)	20 μM(Ki)
DT-diaphorase (无细胞试验)	20 μM(Ki)

体外研究

在体外，DMXAA抑制了纯化的DT-黄心肌酶活性，IC50为62.5 μM，Ki值为20 μM。对于DLD-1人结肠癌细胞系而言，它也能够抑制该酶的活性，IC50值为49.6 μM；然而，DMXAA并未对细胞色素b5还原酶和细胞色素P450还原酶产生显著影响。

此外，DMXAA作为抗病毒药物，在RAW 264.7巨噬细胞中抑制了VSV诱导的细胞毒性，并且也抑制了流感病毒感染。最新研究还表明，DMXAA能够非免疫调节地抑制VEGFR几种激酶成员如人脐静脉内皮细胞中的VEGFR2信号传导。

体内研究

在体内实验中，DMXAA显著延缓了化学致癌物诱导的细胞生长，并延长了肿瘤倍增时间以及从治疗到安乐死的时间。处理携带肿瘤的小鼠后，平均肿瘤倍增时间、平均肿瘤三倍大小的时间及从治疗到安乐死的平均时间分别提高了4.4-倍、1.8-2.7-倍。

DMXAA还能够显著保护感染H1N1流感PR8病毒的小鼠（剂量为200 p.f.u.），使存活率提高至60%，而对照组仅为20%。

反应信息

• 作为反应物：
  描述：

  2,5-己酮可可碱 在 sodium hydroxide 作用下， 以 水 、 丙酮 为溶剂， 生成 9H-占吨-4-乙酸,5,6-二甲基-9-羰基-,盐钠
  参考文献：
  名称：

  [EN] ORGANIC COMPOUNDS
  [FR] COMPOSÉS ORGANIQUES

  摘要：

  本发明提供了一种改进的合成5,6-二甲基-9-氧代-9H-黄色素4-乙酸酯（DMXAA）的过程。该过程产物纯净、无色，适用于大规模生产。

  公开号：

  WO2009156459A1
• 作为产物：
  描述：

  ethyl 2-(5,6-dimethyl-9-oxo-9H-xanthen-4-yl)acetate 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以75%的产率得到2,5-己酮可可碱
  参考文献：
  名称：

  一种5,6-二甲基呫吨酮-4-乙酸的合成方法

  摘要：

  本发明涉及一种5,6‑二甲基呫吨酮‑4‑乙酸的合成方法，首先用2,3‑二甲基苯酚与2,3‑二氯苯甲醛反应生成4‑氯‑5,6‑二甲基呫吨酮，然后与丙二酸二乙酯反应得到5,6‑二甲基呫吨酮‑4‑乙酸乙酯，最后碱性水解得到5,6‑二甲基呫吨酮‑4‑乙酸，该方法所需原料价格适中，收率高，所得产物纯度大于98%。

  公开号：

  CN111662265A

文献信息

• [EN] COMPOUNDS AND COMPOSITIONS COMPRISING CDK INHIBITORS AND METHODS FOR THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS ET COMPOSITIONS COMPRENANT DES INHIBITEURS DES CDK ET MÉTHODES DE TRAITEMENT DU CANCER
  申请人：UNIV GEORGIA STATE RES FOUND

  公开号：WO2010129858A1

  公开（公告）日：2010-11-11

  Disclosed herein are compounds suitable for use as antitumor agents, methods for treating cancer wherein the disclosed compounds are used in making a medicament for the treatment of cancer, methods for treating a tumor comprising, administering to a subject a composition comprising one or more of the disclosed cytotoxic agents, and methods for preparing the disclosed antitumor agents.

  本文披露了适用作抗肿瘤药剂的化合物，用于治疗癌症的方法，其中所披露的化合物用于制备治疗癌症的药物，治疗肿瘤的方法包括向受试者施用包含一种或多种所披露的细胞毒性药剂的组合物，以及制备所披露的抗肿瘤药剂的方法。
• PROTEIN KINASE INHIBITORS
  申请人：Sheppard S. George

  公开号：US20070203143A1

  公开（公告）日：2007-08-30

  Compounds that inhibit protein kinases, compositions containing the compounds and methods of treating diseases using the compounds are disclosed.

  抑制蛋白激酶的化合物、含有这些化合物的组合物以及利用这些化合物治疗疾病的方法被披露。
• [EN] PYRROLOPYRIMIDINES AS FAK AND ALK INHIBITERS FOR TREATMENT OF CANCERS AND OTHER DISEASES<br/>[FR] PYRROLOPYRIMIDINES À TITRE D'INHIBITEURS DE FAK ET D'ALK POUR LE TRAITEMENT DES CANCERS ET AUTRES MALADIES
  申请人：ABBOTT LAB

  公开号：WO2012045195A1

  公开（公告）日：2012-04-12

  Disclosed are compounds which inhibit the activity of focal adhesion kinase (FAK) and anaplastic lymphoma kinase (ALK), compositions containing the compounds, and methods of treating diseases during which FAK and ALK are expressed. The diseases are, for example, cancers.

  揭示了抑制焦点粘附激酶（FAK）和间变性淋巴瘤激酶（ALK）活性的化合物，含有这些化合物的组合物，以及治疗在其中FAK和ALK表达的疾病的方法。这些疾病例如包括癌症。
• NOVEL STING AGONISTS
  申请人：Venenum Biodesign, LLC

  公开号：US20200131209A1

  公开（公告）日：2020-04-30

  The present invention provides compounds of Formula I′: wherein , W, X, Y, Z, Z 1 , Z 2 , R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are effective at modulating the STING protein and thus can be used as medicaments for treating or preventing disorders affected by the agonism of STING.

  本发明提供了式I′的化合物： 其中 , W, X, Y, Z, Z 1 , Z 2 , R 1 , R 2 , R 3 , R 4 和R 5 如本文所定义，或其立体异构体、互变异构体、药学上可接受的盐、前药酯或溶剂化合物形式，其中所有变量均如本文所定义。这些化合物能有效调节STING蛋白，因此可用作治疗或预防受STING激动影响的疾病的药物。
• Composition Containing Novel Glutamic Acid Derivative And Block Copolymer, And Use Thereof
  申请人：Nippon Kayaku Kabushiki Kaisha

  公开号：US20200190101A1

  公开（公告）日：2020-06-18

  Provided is a pharmaceutical preparation that is suitable for more effectively exhibiting the efficacy of a glutamic acid derivative, which is a GGT-recognizable prodrug, by producing a composition including a glutamic acid derivative capable of rapidly releasing a physiologically active substance by being recognized by GGT, or a pharmacologically acceptable salt thereof; and a block copolymer in which a polyethylene glycol segment is linked to a polyamino acid segment with a hydrophobic group. Particularly, the composition based on a glutamic acid derivative that uses an antitumor compound as a physiologically active substance is capable of effectively accumulating the glutamic acid derivative at a tumor affected area, exhibits a superior effect against tumors, and is capable of suppressing the release of a physiologically active substance in bone marrow tissue where the expression ratio of GGT is low. Therefore, side effects such as myelosuppression, which pose a problem in the use of antitumor drugs, may be avoided.

  提供的是一种药物制剂，适用于更有效地展现谷氨酸衍生物的功效，该衍生物是一种GGT可识别的前药，通过制备包括一种能够被GGT识别从而快速释放生理活性物质的谷氨酸衍生物或其药理学可接受的盐的组合物；以及一种嵌段共聚物，其中聚乙二醇段与一个疏水基团连接到一个聚氨基酸段。特别是，基于谷氨酸衍生物的组合物使用抗肿瘤化合物作为生理活性物质，能够有效地在受肿瘤影响的区域积累谷氨酸衍生物，对肿瘤具有优越效果，并能够抑制在GGT表达比例较低的骨髓组织中释放生理活性物质。因此，可以避免使用抗肿瘤药物时可能出现的骨髓抑制等副作用。