磺吡酮 | 57-96-5

• 物质功能分类: 原料药 - 解热镇痛药 - 抗痛风药
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 磺吡酮
• 中文别名: 硫氧唑酮；苯磺保泰松；磺胺吡啶二酮；(±)-磺吡酮；苯磺唑酮；磺吡拉宗；1,2-二苯基-4-(2-(苯亚磺酰)乙基)-3,5-吡唑烷二酮
• 英文名称: 4-[2-(phenylsulfinyl)ethyl]-1,2-diphenyl-3,5-pyrazolidinedione
• 英文别名: Sulfinpyrazone；(+/-)-sulfinpyrazone；sulfflhpyrazone；Sulfinpyrazon；sufinpyrazone；4-[2-(benzenesulfinyl)ethyl]-1,2-diphenylpyrazolidine-3,5-dione
• CAS: 57-96-5
• 化学式: C₂₃H₂₀N₂O₃S
• mdl: MFCD00057279
• 分子量: 404.489
• InChiKey: MBGGBVCUIVRRBF-UHFFFAOYSA-N

物化性质

• 熔点：
  136-137°
• 沸点：
  590.8±42.0 °C(Predicted)
• 密度：
  1.1890 (rough estimate)
• 溶解度：
  极微溶于水，微溶于乙醇（96%）。溶于碱金属氢氧化物的稀溶液。
• 物理描述：
  Solid
• 颜色/状态：
  WHITE TO OFF-WHITE
• 稳定性/保质期：
  STABLE TO LIGHT & AIR
• 解离常数：
  PKA: 2.8
• 碰撞截面：
  193.5 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  76.9
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

尿液中的大部分药物（90%）未发生改变；其余部分以N1-对-羟基苯基代谢物的形式排出...

MOST OF DRUG (90%) IN URINE IS UNCHANGED; REMAINDER IS ELIMINATED AS N1-P-HYDROXYPHENYL METABOLITE...

来源:Hazardous Substances Data Bank (HSDB)

代谢

.../在大鼠体内/ 28%...在尿液中 & 24%...在粪便和胆汁中发现为P-羟基磺吡唑。

.../IN RAT/ 28%...IN URINE & 24%...IN FECES & BILE WAS FOUND AS P-HYDROXYSULFINPYRAZOLE.

来源:Hazardous Substances Data Bank (HSDB)

代谢

.sulfinpyrazone磺吡酮已知的人体代谢物包括.sulfinpyrazone磺吡酮。

Sulfinpyrazone has known human metabolites that include Sulfinpyrazone sulfone.

来源:NORMAN Suspect List Exchange

毒理性

• 相互作用

非选择性尿酸盐转运抑制剂.sulfinpyrazone的URICOSURIC作用与丙磺舒和保泰松的作用相加，但与水杨酸盐的作用相互拮抗。具有将其他有机阴离子从与血浆蛋白广泛结合中移除的能力。从而改变它们在组织中的分布和它们的肾脏排泄。

...URICOSURIC ACTION /OF SULFINPYRAZONE/ IS ADDITIVE TO THAT OF PROBENECID & PHENYLBUTAZONE BUT IS MUTUALLY ANTAGONISTIC TO THAT OF SALICYLATES. ... POSSESSES ABILITY TO DISPLACE OTHER ORG ANIONS THAT ARE BOUND EXTENSIVELY TO PLASMA PROTEINS...THUS ALTERING THEIR DISTRIBUTION TO TISSUES & THEIR RENAL EXCRETION...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

...SULFINPYRAZONE 可能增强胰岛素和口服降糖药的作用...

...SULFINPYRAZONE MAY POTENTIATE ACTIONS OF INSULIN & ORAL HYPOGLYCEMIC AGENTS...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

磺吡酮可能会将磺胺类药物从血浆蛋白结合位点置换出来...

SULFINPYRAZONE MAY DISPLACE SULFONAMIDES FROM PLASMA PROTEIN BINDING SITES...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

超敏反应，通常伴有皮疹和发热，确实会发生.../偶尔/

HYPERSENSITIVITY REACTIONS, USUALLY A RASH WITH FEVER, DO OCCUR.../OCCASIONALLY/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

副作用包括上消化道不适...&, 极少数情况下，贫血，白细胞减少，粒细胞缺乏和血小板减少。

SIDE EFFECTS INCL UPPER GI DISTURBANCES...&, RARELY, ANEMIA, LEUKOPENIA, AGRANULOCYTOSIS, & THROMBOCYTOPENIA.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

...口服给药后吸收良好...与血浆蛋白结合...98-99%。半衰期...静脉注射后血浆中的半衰期约为3小时。口服给药后...促尿酸排泄作用可能持续...10小时。尽管在肾小球滤过时只有很少量...可供过滤，但它会被近端小管分泌并经历很少的被动反向扩散...

...WELL ABSORBED AFTER ORAL ADMIN. ...BOUND TO PLASMA PROTEINS...98-99%. T/2... IN PLASMA AFTER IV INJECTION IS ABOUT 3 HR. AFTER ORAL ADMIN...URICOSURIC EFFECT MAY PERSIST FOR...10 HR. ALTHOUGH LITTLE...IS AVAILABLE FOR FILTRATION @ GLOMERULUS, IT IS SECRETED BY PROXIMAL TUBULE & UNDERGOES LITTLE PASSIVE BACK DIFFUSION...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

大约一半的口服剂量在24小时内出现在尿液中。尿液中的大部分药物（90%）未发生改变；其余部分以代谢物的形式排出...

APPROX HALF OF ORALLY ADMIN DOSE APPEARS IN URINE WITHIN 24 HR. MOST OF DRUG (90%) IN URINE IS UNCHANGED; REMAINDER IS ELIMINATED AS...METABOLITE...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

...在人体内迅速排泄，连同p-羟基化代谢物。血浆半衰期...在大鼠中...16.2小时，并且...18%的腹腔注射剂量...被排入尿液中。人体内血浆半衰期...在1到3小时之间。大鼠主要排泄途径...粪便（剂量的68%）...相当一部分...通过胆汁排泄的被肠道重新吸收。

...RAPIDLY EXCRETED IN MAN, TOGETHER WITH P-HYDROXYLATED METABOLITE. PLASMA T/2...IN RATS...16.2 HR, &...18% OF IP DOSE...WAS EXCRETED INTO URINE. PLASMA T/2 IN MAN...BETWEEN 1 & 3 HR. MAIN ROUTE OF ELIMINATION IN RAT...FECES (68% OF DOSE)...CONSIDERABLE PORTION...EXCRETED IN BILE WAS REABSORBED FROM INTESTINAL TRACT.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

...SULFINPYRAZONE...在大鼠尿液中仅以少量排泄。主要通过胆汁从循环中清除...没有证据表明存在肠肝循环机制。

...SULFINPYRAZONE...IS EXCRETED IN URINE OF RATS TO ONLY A SMALL EXTENT. ... CLEARED FROM CIRCULATION MAINLY THROUGH BILE...NO EVIDENCE OF ENTERO-HEPATIC CIRCULATION MECHANISM.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

未改变的药物在大鼠中的主要排泄产物为28%在尿液中，24%在粪便和胆汁中发现为对羟基磺胺吡唑。大鼠未能以高比例通过尿液排泄药物可能与该物种缺乏尿酸盐排泄特性有关。

UNCHANGED DRUG /IN RAT/ WAS PRINCIPAL EXCRETION PRODUCT & ONLY 28%...IN URINE & 24%...IN FECES & BILE WAS FOUND AS P-HYDROXYSULFINPYRAZOLE. FAILURE OF RAT TO EXCRETE A HIGH PROPORTION OF THE DRUG IN URINE MAY BE RELATED TO ITS LACK OF URICOSURIC PROPERTIES IN THIS SPECIES.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S36
• 危险类别码：
  R22
• WGK Germany：
  3
• 海关编码：
  2933990090
• 危险品运输编号：
  NONH for all modes of transport
• RTECS号：
  UQ8575000
• 危险标志：
  GHS07
• 危险性描述：
  H302
• 危险性防范说明：
  P280,P305+P351+P338
• 储存条件：
  2-8°C

SDS

---

SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : (±)-Sulfinpyrazone
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. : 57-96-5
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

---

SECTION 2: Hazards identification
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008
Acute toxicity, Oral (Category 4), H302
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 Harmful R22
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.
Precautionary statement(s) none
Supplemental Hazard none
Statements
Safety data sheet available on request.
Other hazards - none

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SECTION 3: Composition/information on ingredients
Substances
Synonyms : 1,2-Diphenyl-4-(phenylsulfinylethyl)-3,5-pyrazolidinedione
Formula : C23H20N2O3S
Molecular Weight : 404,48 g/mol
CAS-No. : 57-96-5
EC-No. : 200-357-4
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
Sulfinpyrazone
CAS-No. 57-96-5 Acute Tox. 4; H302 <= 100 %
EC-No. 200-357-4
Hazardous ingredients according to Directive 1999/45/EC
Component Classification Concentration
Sulfinpyrazone
CAS-No. 57-96-5 Xn, R22 <= 100 %
EC-No. 200-357-4
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, nitrogen oxides (NOx), Sulphur 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. Avoid breathing dust.
For personal protection see section 8.
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.

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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
Do not let product enter drains.

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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- no data available
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
LD50 Oral - rat - 358 mg/kg
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: UQ8575000
Gastrointestinal disturbance, Vomiting, Diarrhoea

---

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
no data available

---

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.

---

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

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

Sulfinpyrazone (G-28315, NSC 75925) 是研究最为广泛的血小板COX抑制剂之一，也是一种能在肾脏近端小管中竞争性抑制尿酸重吸收的尿酸排泄剂。

靶点

Target	Value
platelet-release reaction

体外研究

Sulfinpyrazone (G-28315) 刺激纤溶活性。

体内研究

在不同实验条件下，Sulfinpyrazone 发挥显著的电生理学作用。它能提高心室纤颤阈值和中期舒张阈值，并延长有效不应期。在严重缺血性心脏中，该药物可以减弱心肌梗塞对心室纤颤阈值的影响，但在缺血再灌注后则无此效果。此外，在去甲肾上腺素的交感神经体液刺激下，Sulfinpyrazone 具有明显的保护作用。

用途

用作抗痛风药

反应信息

• 作为反应物：
  描述：

  磺吡酮 在 N-fluorobis<(trifluoromethyl)sulfonyl>imide 作用下， 以 氯仿 为溶剂， 以90%的产率得到1,2-diphenyl-4-fluoro-4-<(2-phenylsulfinyl)ethyl>pyrazolidine-3,5-dione
  参考文献：
  名称：

  Electrophilic fluorination of pharmacologically active 1,3-dicarbonyl compounds

  摘要：

  DOI：

  10.1021/jo00041a039
• 作为产物：
  描述：

  1,2-二苯基-4-[2-(苯硫酰)乙基]-3,5吡唑烷 生成 磺吡酮
  参考文献：
  名称：

  CHURCH, G. A.;CHOU, CHIH, H.

  摘要：

  DOI：

文献信息

• Eflornithine Prodrugs, Conjugates and Salts, and Methods of Use Thereof
  申请人：Xu Feng

  公开号：US20100120727A1

  公开（公告）日：2010-05-13

  In one aspect, the present invention provides a composition of a covalent conjugate of an eflornithine analog with an anti-inflammatory drug. In another aspect, the present invention provides a composition of an eflornithine prodrug. In another aspect, the present invention provides a composition of an eflornithine or its derivatives aspirin salt. In another aspect, the present invention provides methods for treating or preventing cancer using the conjugates or salts of eflornithine analogs or eflornithine prodrugs.

  在一个方面，本发明提供了一种氟硝西汀类似物与抗炎药物的共价结合物的组合物。在另一个方面，本发明提供了一种氟硝西汀前药的组合物。在另一个方面，本发明提供了一种氟硝西汀或其衍生物水杨酸盐的组合物。在另一个方面，本发明提供了使用氟硝西汀类似物或氟硝西汀前药的共轭物或盐来治疗或预防癌症的方法。
• SULFOXIMINE SUBSTITUTED QUINAZOLINES FOR PHARMACEUTICAL COMPOSITIONS
  申请人：BLUM Andreas

  公开号：US20140135309A1

  公开（公告）日：2014-05-15

  This invention relates to novel sulfoximine substituted quinazoline derivatives of formula I wherein Ar, R 1 and R 2 are as defined herein, and their use as MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.

  这项发明涉及公式I的新型磺酰胺取代的喹唑啉衍生物，其中Ar、R1和R2如本文所定义，并且它们作为MNK1（MNK1a或MNK1b）和/或MNK2（MNK2a或MNK2b）激酶抑制剂的用途，含有这些化合物的药物组合物，以及将其用作治疗或改善MNK1（MNK1a或MNK1b）和/或MNK2（MNK2a或MNK2b）介导的疾病的药剂的方法。
• [EN] SULFOXIMINE SUBSTITUTED QUINAZOLINES FOR PHARMACEUTICAL COMPOSITIONS<br/>[FR] QUINAZOLINES SUBSTITUÉES PAR SULFOXIMINE POUR COMPOSITIONS PHARMACEUTIQUES
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2014072244A1

  公开（公告）日：2014-05-15

  This invention relates to novel sulfoximine substituted quinazoline derivatives of formula (I), wherein Ar, R1 and R2 are as defined in the description and claims, and their use as MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.

  这项发明涉及一种新型的配方(I)的磺酰胺取代喹唑啉衍生物，其中Ar、R1和R2如描述和声明中所定义，并且它们作为MNK1（MNK1a或MNK1b）和/或MNK2（MNK2a或MNK2b）激酶抑制剂的用途，含有这些化合物的药物组合物，以及将其用作治疗或改善MNK1（MNK1a或MNK1b）和/或MNK2（MNK2a或MNK2b）介导的疾病的药剂的方法。
• [EN] MACROCYCLIC FACTOR VIIA INHIBITORS<br/>[FR] INHIBITEURS MACROCYCLIQUES DU FACTEUR VIIA
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2013184734A1

  公开（公告）日：2013-12-12

  The present invention provides compounds of Formula (I): as defined in the specification and compositions comprising any of such novel compounds. These compounds are Factor VIIa inhibitors which may be used as medicaments.

  本发明提供了如规范中定义的Formula (I)的化合物，以及包含任何此类新化合物的组合物。这些化合物是Factor VIIa抑制剂，可用作药物。
• PYRIMIDINYL AND 1,3,5-TRIAZINYL BENZIMIDAZOLES AND THEIR USE IN CANCER THERAPY
  申请人：Rewcastle Gordon William

  公开号：US20110009405A1

  公开（公告）日：2011-01-13

  Provided herein are pyrimidinyl and 1,3,5-triazinyl benzimidazoles of Formula I, and their pharmaceutical compositions, preparation, and use as agents or drugs for cancer therapy, either alone or in combination with radiation and/or other anticancer drugs.

  本文提供了式I的嘧啶基和1,3,5-三嗪基苯并咪唑化合物，以及它们的药物组合物、制备方法，以及作为抗癌治疗药物或药剂的用途，可以单独使用，也可以与放疗和/或其他抗癌药物联合使用。

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