普林贝瑞 - CAS号 524684-52-4

物化性质

熔点：

250-252 ºC
沸点：

451.6±45.0 °C(Predicted)
密度：

1.413
溶解度：

二甲基亚砜：≥25mg/mL

计算性质

辛醇/水分配系数(LogP)：

3.6
重原子数：

20
可旋转键数：

2
环数：

3.0
sp3杂化的碳原子比例：

0.0
拓扑面积：

66.5
氢给体数：

2
氢受体数：

5

安全信息

WGK Germany：

3
储存条件：

2-8℃

SDS

SDS：67da0c387b0503335fad6a16ed25b24d

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : ERB-041
CAS-No. : 524684-52-4

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)
Eye irritation (Category 2)
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Harmful if swallowed. Irritating to eyes.
Label elements
Labelling according Regulation (EC) No 1272/2008 [CLP]
Pictogram
Signal word Warning
Hazard statement(s)
Harmful if swallowed.
Causes serious eye irritation.
Precautionary statement(s)
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 Irritating to eyes.
S-phrase(s)
S26 In case of contact with eyes, rinse immediately with plenty of water and
seek medical advice.
Other hazards - none

Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Synonyms : 2-(3-Fluoro-4-hydroxyphenyl)-7-vinyl-1,3-benzoxazol-5-ol
Prinaberel
Formula : C15H10FNO3
Molecular Weight : 271,24 g/mol

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
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

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

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. 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.

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

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).

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: 4,161
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

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

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 Causes serious 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

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

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.

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

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

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

Prinaberel (ERB-041) 是一种有效的选择性雌激素受体 β (ERβ) 激动剂，对人、大鼠和小鼠 ERβ 的 IC50 分别为 5.4 nM、3.1 nM 和 3.7 nM。Prinaberel 对 ERβ 的选择性是 ERα 的 200 倍以上。Prinaberel 是有效的皮肤癌化学预防剂，可通过抑制 WNT/β-catenin 信号通路发挥作用，并能诱导卵巢癌细胞凋亡。

靶点

组织	IC50 (nM)
hERβ	5.4
rat ERβ	3.1
mouse ERβ	3.7
hERα	1200
mouse ERα	750
rat ERα	620

体外研究

Prinaberel (ERB-041) 在 0-60 µM（24 小时）浓度下处理人类鳞状细胞癌（SCC）细胞，可诱导细胞分化、细胞周期停滞，并减少集落形成。Prinaberel 显著减少了 A431 细胞中炎症调节蛋白 p-NFκBp65、iNOS 和 COX-2 的表达；Prinaberel 通过抑制磷酸化 PI3K 和 AKT，增强了 E-cadherin 表达并减少了 A431 细胞的迁移。Prinaberel 在 0.01-10 µM 浓度下以剂量和时间依赖性方式抑制细胞增殖。Prinaberel（10 µM；48 小时）促进 SKOV-3 肺癌细胞凋亡。

Western Blot 分析

细胞系	浓度 (µM)	孵育时间 (小时)	结果
A431	0, 20, 40, 60	24	G1 cyclins (D1, D2, D3) 和 CDK4 的表达减少

细胞增殖试验

细胞系	浓度 (µM)	孵育时间 (小时)	结果
SKOV-3, A2780CP 或 OVCAR-3	0.01, 0.1, 10	24-48	显著抑制细胞增殖

体内研究

Prinaberel（2 mg/鼠；外用，紫外线照射前 30 分钟给药，持续 30 周）可抑制 SKH-1 毛发缺失小鼠的鳞状细胞癌发生。Prinaberel 减少了紫外线诱导皮肤肿瘤的增殖和血管生成，并诱导其凋亡。Prinaberel 抑制了紫外线诱导皮肤肿瘤中的促炎信号通路，通过 PI3K-AKT 途径和 WNT 信号抑制了肿瘤侵袭性。

动物模型

模型	年龄	剂量	给药方式	结果
SKH-1 毛发缺失小鼠	六至八周女鼠	2 mg/鼠，200 µl 酒精	紫外线照射前 30 分钟外用	减轻紫外线诱导皮肤肿瘤的发展

上下游信息

上游原料

中文名称	英文名称	CAS号	化学式	分子量
——	5-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-{[tert-butyl(dimethyl)silyl]oxy}-3-fluorophenyl)-7-vinyl-1,3-benzoxazole	544704-81-6	C₂₇H₃₈FNO₃Si₂	499.773
7-溴-2-(3-氟-4-羟基苯基)-1,3-苯并恶唑-5-醇	2-(3-Fluoro-4-hydroxyphenyl)-7-bromobenzooxazol-5-ol	544704-73-6	C₁₃H₇BrFNO₃	324.106
7-溴-2-(3-氟-4-甲氧基苯基)-5-甲氧基-1,3-苯并恶唑	7-bromo-2-(3-fluoro-4-methoxyphenyl)-5-methoxy-1,3-benzoxazole	544704-75-8	C₁₅H₁₁BrFNO₃	352.16

下游产品

中文名称	英文名称	CAS号	化学式	分子量
——	2-(3'-fluoro-4'-sulfate-phenyl)-7-vinyl-1,3-benzoxazol-5-ol	877172-75-3	C₁₅H₁₀FNO₆S	351.312
——	2-fluoro-4-(5-hydroxy-7-vinylbenzo[d]oxazol-2-yl)phenyl dihydrogen phosphate	1178586-92-9	C₁₅H₁₁FNO₆P	351.228
——	2-(3-fluoro-4-tert-butyldimethylsilyloxyphenyl)-7-vinylbenzooxazol-5-ol	1030596-32-7	C₂₁H₂₄FNO₃Si	385.51
——	2-[3-fluoro-4-(phosphonooxy)phenyl]-7~vinyl-1,3-benzoxazol-5-yl dihydrogen phosphate	1178586-96-3	C₁₅H₁₂FNO₉P₂	431.208
——	5-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-{[tert-butyl(dimethyl)silyl]oxy}-3-fluorophenyl)-7-vinyl-1,3-benzoxazole	544704-81-6	C₂₇H₃₈FNO₃Si₂	499.773
——	4-bromo-2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3-benzoxazol-5-ol	——	C₁₅H₉BrFNO₃	350.144
——	2-{4-[(diethoxyphosphoryl)oxy]-3-fluorophenyl}-7-vinyl-1,3-benzoxazol-5-yl diethyl phosphate	1178586-95-2	C₂₃H₂₈FNO₉P₂	543.423
——	4,6-dibromo-2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3-benzoxazol-5-ol	——	C₁₅H₈Br₂FNO₃	429.04
——	2-(3'-fluoro-4'-glucuronide-phenyl)-7-vinyl-1,3-benzoxazol-5-ol	——	C₂₁H₁₈FNO₉	447.374

反应信息

作为反应物：

描述：

普林贝瑞在水作用下，以乙醇为溶剂，反应 1.67h，以96.11%的产率得到2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3-benzoxazol-5-ol monohydrate

参考文献：

名称：

Liquid and Semi-Solid Pharmaceutical Formulations and Processes

摘要：

本发明涉及Formula I药理活性剂的液体或半固体制剂，该药理活性剂是雌激素受体调节剂，以及其制药组合物和制备过程。

公开号：

US20070207201A1
作为产物：

描述：

3-氟-4-甲氧基苯甲酸在吡啶、氯化亚砜、二氯双(三邻甲苯膦)合钯(II) 、对二甲苯、三溴化硼、对甲苯磺酸、 N,N-二甲基甲酰胺作用下，以二氯甲烷、乙二醇二乙醚为溶剂，反应 52.0h，生成普林贝瑞

参考文献：

名称：

Design and Synthesis of Aryl Diphenolic Azoles as Potent and Selective Estrogen Receptor-β Ligands

摘要：

New diphenolic azoles as highly selective estrogen receptor-beta agonists are reported. The more potent and selective analogues of these series have comparable binding affinities for ERbeta as the natural ligand 17beta-estradiol but are > 100-fold selective over ERalpha. Our design strategy not only followed a traditional SAR approach but also was supported by X-ray structures of ERbeta cocrystallized with various ligands as well as molecular modeling studies. These strategies enabled us to take advantage of a single conservative residue substitution in the ligand-binding pocket, ERalpha Met(421) --> ERbeta Ile(373), to optimize ERbeta selectivity. The 7-position-substituted benzoxazoles (Table 5) were the most selective ligands of both azole series, with ERB-041 (117) being >200-fold selective for ERbeta. The majority of ERbeta selective agonists tested that were at least similar to50-fold selective displayed a consistent in vivo profile: they were inactive in several models of classic estrogen action (uterotrophic, osteopenia, and vasomotor instability models) and yet were active in the HLA-B27 transgenic rat model of inflammatory bowel disease. These data suggest that ERbeta-selective agonists are devoid of classic estrogenic effects and may offer a novel therapy to treat certain inflammatory conditions.

DOI：

10.1021/jm049719y

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文献信息

[EN] COMPOUNDS AND COMPOSITIONS FOR TREATING NEURODEGENERATIVE DISEASES<br/>[FR] COMPOSÉS ET COMPOSITIONS UTILISÉS POUR TRAITER LES MALADIES NEURODÉGÉNÉRATIVES

申请人：ACADIA PHARM INC

公开号：WO2014125121A1

公开（公告）日：2014-08-21

The present application relates to a composition comprising a selective androgen modulating compound of formula (I) and selective estrogen receptor β agonist of formula (II). The present application also relates to the use of a selective androgen modulating compound of formula (I) in combination with a selective estrogen receptor β agonist of formula (II) in the treatment or prevention of neurodegenerative diseases or disorders,such as Alzheimer's disease, Huntigton's disease, Parkinson's disease, depression, anxiety, multiple sclerosis, symptoms associated with or caused by multiple sclerosis, and acute or chronic pain.

本申请涉及一种包含公式（I）的选择性雄激素调节化合物和公式（II）的选择性雌激素受体β激动剂的组合物。本申请还涉及将公式（I）的选择性雄激素调节化合物与公式（II）的选择性雌激素受体β激动剂结合使用，用于治疗或预防神经退行性疾病或障碍，例如阿尔茨海默病、亨廷顿病、帕金森病、抑郁症、焦虑症、多发性硬化症、与多发性硬化症相关或由其引起的症状，以及急性或慢性疼痛。
[EN] PHOSPHATE DERIVATIVES OF SUBSTITUTED BENZOXAZOLES<br/>[FR] DÉRIVÉS PHOSPHATE DE BENZOXAZOLES SUBSTITUÉS

申请人：WYETH CORP

公开号：WO2009100335A1

公开（公告）日：2009-08-13

The present invention relates to phosphate derivatives of estrogen receptor beta agonists, compositions thereof, preparations thereof, and uses thereof. Formula (I).

本发明涉及雌激素受体β激动剂的磷酸酯衍生物，其组成物，制备物和用途。公式（I）。
Prodrug substituted benzoxazoles as estrogenic agents

申请人：Elmarakby Sayed

公开号：US20060046968A1

公开（公告）日：2006-03-02

This invention provides estrogen receptor modulators of formula I, having the structure wherein Q, Q 2 , R 1 , R 2 , R 2a , R 3 , R 3a , and X as defined in the specification, or a pharmaceutically acceptable salt thereof.

这项发明提供了具有以下结构的公式I的雌激素受体调节剂，其中Q、Q2、R1、R2、R2a、R3、R3a和X如规范中定义，或其药用可接受盐。
PHARMACEUTICAL COMPOSITIONS AND METHODS OF PREVENTING, TREATING, OR INHIBITING INFLAMMATORY DISEASES, DISORDERS, OR CONDITIONS OF THE SKIN, AND DISEASES, DISORDERS, OR CONDITIONS ASSOCIATED WITH COLLAGEN DEPLETION

申请人：CHANG Chien-Neng

公开号：US20090010884A1

公开（公告）日：2009-01-08

The present invention provides compositions and methods for preventing, treating, or inhibiting inflammatory diseases, disorders, or conditions of the skin, and diseases, disorders, or conditions associated with collagen depletion using one or more estrogenic agents.

本发明提供了使用一个或多个雌激素类药物预防、治疗或抑制皮肤炎症性疾病、紊乱或状况以及与胶原蛋白流失相关的疾病、紊乱或状况的组合物和方法。
Substituted benzoxazoles as estrogenic agents

申请人：Wyeth

公开号：US20030199562A1

公开（公告）日：2003-10-23

This invention provides estrogen receptor modulators of formula I, having the structure 1 wherein R 1 , R 2 , R 2a , R 3 , R 3a , and R 4 , and X as defined in the specification, or a pharmaceutically acceptable salt thereof.

这项发明提供了具有结构1的式I的雌激素受体调节剂，其中R1、R2、R2a、R3、R3a和R4以及规范中定义的X，或其药用可接受盐。

普林贝瑞 | 524684-52-4

分子结构分类