脑益嗪 | 81267-65-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 中文名称: 脑益嗪
• 中文别名: 脱氢雌马酚；3-(4-羟基苯基)-2H-1-苯并吡喃-7-醇
• 英文名称: idronoxil
• 英文别名: phenoxodiol；Dehydroequol；3-(4-hydroxyphenyl)-2H-chromen-7-ol；haginin E
• CAS: 81267-65-4
• 化学式: C₁₅H₁₂O₃
• 分子量: 240.258
• InChiKey: ZZUBHVMHNVYXRR-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMSO：可溶10mg/mL，澄清

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  49.7
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 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：
  存储条件：2-8°C，干燥，密封。

SDS

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SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : Phenoxodiol
REACH No. : A registration number is not available for this substance as the substance
or its uses are exempted from registration, the annual tonnage does not
require a registration or the registration is envisaged for a later
registration deadline.
CAS-No. : 81267-65-4
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
Classification according to Regulation (EC) No 1272/2008
Acute toxicity, Oral (Category 4), H302
Acute aquatic toxicity (Category 1), H400
For the full text of the H-Statements mentioned in this Section, see Section 16.
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Xn, N Harmful, Dangerous for the R22, R50
environment
For the full text of the R-phrases mentioned in this Section, see Section 16.
Label elements
Labelling according Regulation (EC) No 1272/2008
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
Other hazards - none

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SECTION 3: Composition/information on ingredients
Substances
Synonyms : 3-(4-Hydroxyphenyl)-2H-1-benzopyran-7-ol
Dehydroequol
NV 06
Haginin E
Idronoxil
Formula : C15H12O3
Molecular Weight : 240,25 g/mol
CAS-No. : 81267-65-4
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
PHENOXODIOL
Acute Tox. 4; Aquatic Acute 1; -
H302, H400
For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16

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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
The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in
section 11
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 vapours, mist or gas. Ensure
adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.
For personal protection see section 8.
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.
For precautions see section 2.2.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Specific end use(s)
A part from the uses mentioned in section 1.2 no other specific uses are stipulated

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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).
Control of environmental exposure
Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into
the environment must be avoided.

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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) Evapouration 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: 2,46
octanol/water
p) Auto-ignition 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
Stable under recommended storage conditions.
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
In the event of fire: see section 5

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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 sensitisation
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
Additional Information
RTECS: Not available
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.

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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
PBT/vPvB assessment not available as chemical safety assessment not required/not conducted
Other adverse effects
Very toxic to aquatic life.

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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. (PHENOXODIOL)
IMDG: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S. (PHENOXODIOL)
IATA: Environmentally hazardous substance, solid, n.o.s. (PHENOXODIOL)
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
For this product a chemical safety assessment was not carried out

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SECTION 16: Other information
Full text of H-Statements referred to under sections 2 and 3.
Acute Tox. Acute toxicity
Aquatic Acute Acute aquatic toxicity
H302 Harmful if swallowed.
H400 Very toxic to aquatic life.
Full text of R-phrases referred to under sections 2 and 3
R22 Harmful if swallowed.
R50 Very toxic to aquatic organisms.
Further information
Copyright 2013 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

Phenoxodiol（Haginin E、Idronoxil、Dehydroequol、NV 06、PXD）是一种具有抗肿瘤活性的异黄酮类似物。它能够激活 caspase 系统，抑制 XIAP（X-连锁凋亡抑制蛋白），并破坏 FLICE 抑制蛋白 (FLIP) 的表达，从而导致肿瘤细胞凋亡。此外，Phenoxodiol 还能抑制 DNA 旋转酶 II。

靶点

Target	Value
Caspase
XIAP
FLIP
Topo II

反应信息

• 作为反应物：
  描述：

  脑益嗪 在 盐酸 、 potassium carbonate 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 54.33h， 生成 (E)-N-methyl-2-(1-(4-(7-((E)-2-(2-(methylcarbamothioyl)hydrazono)propoxy)-2H-chromen-3-yl)phenoxy)propan-2-ylidene)hydrazine-1-carbothioamide
  参考文献：
  名称：

  异黄酮-硫半碳杂化物杂化物的合成及其抗肿瘤活性的评估。

  摘要：

  苯氧二酚是具有有效的抗肿瘤活性的异黄酮。在这项研究中，通过苯氧酚与硫代氨基脲的缩合反应合成了一系列新颖的单取代和二取代的苯氧二醇-硫代半脲杂化物。评估了杂种对神经母细胞瘤SKN-BE（2）C，三阴性乳腺癌MDA-MB-231和胶质母细胞瘤U87癌细胞系的体外抗增殖活性。单取代的杂种对所有三种癌细胞系表现出有效的抗增殖活性，而双取代的杂种则活性较低。进一步研究了选定的单取代杂种对正常MRC-5人肺成纤维细胞的细胞毒性，与酚氧二醇相比，它鉴定了两种对癌细胞具有比普通细胞优越的选择性的杂种。这表明单取代的苯氧二酚-硫代半碳杂化物杂化物作为抗癌剂具有广阔的发展潜力。

  DOI：

  10.1016/j.bmcl.2017.04.002
• 作为产物：
  描述：

  tetra-hydrodaidzein 以 苯 为溶剂， 生成 脑益嗪
  参考文献：
  名称：

  Therapeutic methods and compositions involving isoflavones

  摘要：

  描述了包含由一般式（1）描述的异黄酮化合物的治疗方法、组合物和食品，其中Z为H，R1为H，或RACO，其中RA为C1-10烷基或氨基酸，R2为H，OH，或ORB，其中RB为氨基酸，或CORA，其中RA如前所定义，W为H，A为H或OH，B从（a），（b），（c）中选择，或W为H，A和B一起形成从（d）中选择的六元环，或W，A和B与它们相关联的基团一起构成（e），或W和A与它们相关联的基团一起构成（f），B为（g），其中R3为H，CORA，其中RA如前所定义，CO2RC，其中RC为C1-10烷基，或CORB，其中RB如前所定义，R4为H，CORD，其中RD为H，OH，C1-10烷基或氨基酸，CO2RC，其中RC如前所定义，CORE，其中RE为H，C1-10烷基或氨基酸，COOH，CORC，其中RC如前所定义，或CONHRE，其中RE如前所定义，R5为H，CORC，其中RC如前所定义，或CORCORE，其中RC和RE如前所定义，两个R5基团连接到相同基团时，它们相同或不同，R6为H或羟基C1-10烷基，X优选为O，但也可以是N或S，Y为（h），其中R7为H或C1-10烷基。

  公开号：

  US20020198248A1
• 作为试剂：
  描述：

  7-Benzyloxy-4'-methoxy-Δ³-isoflaven 、 n-Bu4NI BCl3 、 三氯化硼 在 脑益嗪 、 7-羟基-3-(4-甲氧基苯基)-2H-1-苯并吡喃 作用下， 以to give haginin E (compound 2a) at a yield of 79% and 7-hydroxy-3-(4-methoxyphenyl)-2H-1-benzopyran (4′-O-methyl haginin E, compound 2b) at a yield of 81%的产率得到脑益嗪
  参考文献：
  名称：

  Processes for preparing isoflavonoids using 7-benzyloxy-3-(4-methoxyphenyl)-2H-1-benzopyran as a starting material

  摘要：

  本文公开了一种制备异黄酮的方法，尤其是haginin E、equol、daidzein、formononetin等，其中7-苄氧基-3-(4-甲氧基苯基)-2H-1-苯并吡喃被用作共同起始材料。

  公开号：

  US07875735B2

文献信息

• Synthesis, anti-cancer and anti-inflammatory activity of novel 2-substituted isoflavenes
  作者：Eleanor Eiffe、Eddy Pasquier、Maria Kavallaris、Cristan Herbert、David StC Black、Naresh Kumar

  DOI：10.1016/j.bmc.2014.08.010

  日期：2014.10

  2-substituted isoflavenes were synthesised via nucleophilic addition to isoflavylium salts. Twelve of the newly synthesised isoflavenes, along with the unsubstituted parent isoflavene, were tested in cell viability assays against the SHEP neuroblastoma and MDA-MB-231 breast adenocarcinoma cell lines. While the 2-substituted isoflavenes displayed a range of anti-proliferative activities, in most cases

  通过亲核加成到异黄酮盐中合成了十五种新颖的2-取代的异黄酮。在针对SHEP神经母细胞瘤和MDA-MB-231乳腺癌细胞系的细胞活力测定中，测试了十二种新合成的异黄酮以及未取代的母体异黄酮。尽管2-取代的异黄酮具有一系列抗增殖活性，但在大多数情况下，它们的活性低于未取代的异黄酮（IC 50  = 9.9μMvs SHEP； IC 50  = 33μMvs MDA-MB-231）。然而，衍生自异黄酮盐5与对甲氧基苯乙酮反应的化合物7f对乳腺癌细胞显示出改善的抗增殖活性（IC50  = 7.6μM）。此外，化合物7f以及类似物7a，7c，11d和14抑制LPS激活的RAW 264.7细胞中白介素6的产生。
• [EN] 2-SUBSTITUTED ISOFLAVONOID COMPOUNDS, MEDICAMENTS AND USES<br/>[FR] COMPOSÉS ISOFLAVONOÏDES SUBSTITUÉS EN POSITION 2, MÉDICAMENTS ET UTILISATIONS
  申请人：NOVOGEN RES PTY LTD

  公开号：WO2009003229A1

  公开（公告）日：2009-01-08

  2-Substituted isoflavonoid compounds and pharmaceutical compositions containing same are useful as anti-inflammatory agents and antioxidants and for the treatment of related diseases and conditions.

  2-取代异黄酮化合物和含有这些化合物的药物组合物可用作抗炎剂和抗氧化剂，用于治疗相关疾病和症状。
• Synthesis, biological evaluation and structure–activity relationship studies of isoflavene based Mannich bases with potent anti-cancer activity
  作者：Yilin Chen、Shelley L. Cass、Samuel K. Kutty、Eugene M.H. Yee、Daniel S.H. Chan、Christopher R. Gardner、Orazio Vittorio、Eddy Pasquier、David StC. Black、Naresh Kumar

  DOI：10.1016/j.bmcl.2015.09.027

  日期：2015.11

  prominent anti-proliferative effects against SHEP neuroblastoma and MDA-MB-231 breast adenocarcinoma cell lines. Further cytotoxicity studies against MRC-5 normal lung fibroblast cells showed that the isoflavene analogues were selective towards cancer cells.

  苯氧二酚是异黄酮天然产物黄豆苷元的类似物，是一种有效的抗癌药，已被研究用于治疗激素依赖性癌症。该分子支架在不同的曼尼希条件下与不同的伯胺和仲胺反应，生成苯并恶嗪或氨甲基取代的类似物。这些过程使得能够产生结构-活性关系（SAR）研究所需的各种类似物。所得的曼尼希碱显示出对SHEP神经母细胞瘤和MDA-MB-231乳腺癌细胞的显着抗增殖作用。针对MRC-5正常肺成纤维细胞的进一步细胞毒性研究表明，异黄酮类似物对癌细胞具有选择性。
• Structure–Activity Relationship of Phytoestrogen Analogs as ERα/β Agonists with Neuroprotective Activities
  作者：Hye Won Cho、Hyo Jin Gim、Hua Li、Lalita Subedi、Sun Yeou Kim、Jae-Ha Ryu、Raok Jeon

  DOI：10.1248/cpb.c20-00706

  日期：2021.1.1

  A set of isoflavononid and flavonoid analogs was prepared and evaluated for estrogen receptor α (ERα) and ERβ transactivation and anti-neuroinflammatory activities. Structure–activity relationship (SAR) study of naturally occurring phytoestrogens, their metabolites, and related isoflavone analogs revealed the importance of the C-ring of isoflavonoids for ER activity and selectivity. Docking study suggested putative binding modes of daidzein 2 and dehydroequol 8 in the active site of ERα and ERβ, and provided an understanding of the promising activity and selectivity of dehydroequol 8. Among the tested compounds, equol 7 and dehydroequol 8 were the most potent ERα/β agonists with ERβ selectivity and neuroprotective activity. This study provides knowledge on the SAR of isoflavonoids for further development of potent and selective ER agonists with neuroprotective potential.

  一组异黄酮和类黄酮类似物被制备并评估了其对雌激素受体α（ERα）和ERβ的转录激活作用及抗神经炎症活性。对天然存在的植物雌激素及其代谢物和相关异黄酮类似物的结构－活性关系（SAR）研究显示，异黄酮的C环对ER活性和选择性的重要性。对接研究表明，黄酮醇2和脱氢异黄酮8在ERα和ERβ活性位点的假定结合模式，揭示了脱氢异黄酮8的良好活性和选择性。在测试的化合物中，异黄酮7和脱氢异黄酮8是最有效的ERα/β激动剂，具有ERβ选择性和神经保护活性。本研究为进一步开发具有神经保护潜力的强效和选择性ER激动剂提供了关于异黄酮的SAR知识。
• Processes for Preparing Isoflavonoids using 7-benzyloxy-3-(4-methoxyphenyl)-2H-1-benzopyran as a Starting Material
  申请人：Wang Eng-Chi

  公开号：US20100298581A1

  公开（公告）日：2010-11-25

  Disclosed herein are processes for the preparation of isoflavonoids, in particular haginin E, equol, daidzein, formononetin and the like, in which 7-benzyloxy-3-(4-methoxyphenyl)-2H-1-benzopyran is used as a common starting material.

  本文披露了一种制备异黄酮类化合物的方法，特别是制备haginin E、equol、daidzein、formononetin等化合物的方法，其中7-苄氧基-3-(4-甲氧基苯基)-2H-1-苯并吡喁被用作共同的起始原料。