2-甲硫基-4-溴嘧啶 | 959236-97-6

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 中文名称: 2-甲硫基-4-溴嘧啶
• 中文别名: 4-溴-2-甲硫基嘧啶；2-甲基硫代-4-溴嘧啶
• 英文名称: 4-bromo-2-(methylthio)pyrimidine
• 英文别名: 4-bromo-2-(methylsulfanyl)pyrimidine；4-bromo-2-methylsulfanylpyrimidine
• CAS: 959236-97-6
• 化学式: C₅H₅BrN₂S
• 分子量: 205.078
• InChiKey: TZSQAGYDWPPKPE-UHFFFAOYSA-N

物化性质

• 熔点：
  30-40℃
• 沸点：
  281℃
• 密度：
  1.72
• 闪点：
  124℃

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  51.1
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  8
• 海关编码：
  2933599090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H317,H319

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4-Bromo-2-(methylthio)pyrimidine
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H314: Causes severe skin burns and eye damage
H318: Causes serious eye damage
P260: Do not breathe dust/fume/gas/mist/vapours/spray
P303+P361+P353: IF ON SKIN (or hair): Remove/Take off immediately all contaminated clothing. Rinse skin with
water/shower
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P301+P330+P331: IF SWALLOWED: Rinse mouth. Do NOT induce vomiting
P405: Store locked up

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Section 3. Composition/information on ingredients.
Ingredient name: 4-Bromo-2-(methylthio)pyrimidine
CAS number: 959236-97-6

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Storage: Store in closed vessels, refrigerated.

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C5H5BrN2S
Molecular weight: 205.1

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen bromide, sulfur oxides.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
UN Number: UN1759 Class: 8 Packing group: III
Proper shipping name: CORROSIVE SOLIDS, N.O.S. (4-Bromo-2-(methylthio)pyrimidine)

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  2-甲硫基-4-溴嘧啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 双(三甲基硅烷基)氨基钾 、 sodium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.5h， 生成 (S)-1-(2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-(methylthio)pyrimidin-4-yl)pyridin-2(1H)-one
  参考文献：
  名称：

  Design, Synthesis, and Antitumor Activity Evaluation of Proteolysis-Targeting Chimeras as Degraders of Extracellular Signal-Regulated Kinases 1/2

  摘要：

  单独或与其他靶点联合抑制细胞外信号调节激酶 1/2（ERK1/2）已成为治疗各种人类肿瘤的一种很有前景的策略。除了开发抑制剂，开发ERK1/2降解剂也是降低其活性的另一种方法。我们合成了蛋白水解靶向嵌合体（PROTACs）作为有效的ERK1/2降解剂，其中B1-10J表现出很高的降解活性，对HCT116细胞的DC50为102 nM，细胞毒性IC50为2.2 μM。此外，B1-10J 还能剂量依赖性地抑制肿瘤细胞的迁移。裸鼠异种移植实验表明，B1-10J 可抑制 HCT116 肿瘤细胞的生长，每天 25 毫克/千克的剂量可使肿瘤显著消退。

  DOI：

  10.3390/ijms242216290
• 作为产物：
  描述：

  2-甲硫基-4-氯嘧啶 在 三甲基溴硅烷 作用下， 以 乙腈 为溶剂， 反应 30.0h， 以96%的产率得到2-甲硫基-4-溴嘧啶
  参考文献：
  名称：

  咪唑并[1,2-b]哒嗪骨架作为蛋白激酶抑制剂的探索

  摘要：

  合成了3,6-二取代的咪唑并[1,2-b]哒嗪衍生物，以鉴定各种真核激酶的新抑制剂，包括哺乳动物和原生动物激酶。在作为激酶抑制剂测试的咪唑并[1,2-b]哒嗪中，几种衍生物对DYRK和CLK具有选择性，IC 50  <100 nM。几种疟原虫和利什曼原虫等寄生虫的激酶组的特征表明，这些寄生虫的蛋白激酶与宿主的蛋白激酶之间存在着巨大的差异。这使我们研究了所制备化合物针对11种寄生激酶的活性。3,6-二取代的咪唑并[1,2-b]哒嗪显示出对恶性疟原虫CLK1（PfCLK1）。发现化合物20a是对CLK1（IC 50  = 82 nM），CLK4（IC 50  = 44 nM），DYRK1A（IC 50  = 50 nM）和Pf CLK1（IC 50  = 32 nM）最具选择性的产物。还测试了该化合物对亚马逊利什曼原虫的抵抗力。通过使用成神经母细胞瘤细胞系进行的活力分析判断，数种化合物在较高浓

  DOI：

  10.1016/j.ejmech.2016.09.064

文献信息

• [EN] INHIBITORS OF WDR5 PROTEIN-PROTEIN BINDING<br/>[FR] INHIBITEURS DE LA LIAISON PROTÉINE WDR5-PROTÉINE
  申请人：ONTARIO INST FOR CANCER RES (OICR)

  公开号：WO2017147700A1

  公开（公告）日：2017-09-08

  The present application is directed to compounds of Formula I: compounds comprising these compounds and their uses, for example as medicaments for the treatment of diseases, disorders or conditions mediated or treatable by inhibition of binding between WDR5 protein and its binding partners.

  本申请涉及到Formula I的化合物：包括这些化合物的化合物及其用途，例如作为治疗由于抑制WDR5蛋白与其结合伙伴之间结合而介导或可治疗的疾病、疾病或症状的药物。
• Structure-Activity Relationships of 2-Sufonylpyrimidines as Quorum-Sensing Inhibitors to Tackle Biofilm Formation and eDNA Release of<i>Pseudomonas aeruginosa</i>
  作者：Andreas Thomann、Christian Brengel、Carsten Börger、Dagmar Kail、Anke Steinbach、Martin Empting、Rolf W. Hartmann

  DOI：10.1002/cmdc.201600419

  日期：2016.11.21

  Herein we report the structure–activity relationships of 2‐sulfonylpyrimidines, which were previously identified as dual‐target inhibitors of the PQS receptor PqsR and the PQS synthase PqsD. The SAR elucidation was guided by a combined approach using ligand efficiency and ligand lipophilicity efficiency to select the most promising compounds. In addition, the most effective inhibitors were rationally modified

  耐药的铜绿假单胞菌（PA）菌株正在增加，使目前的抗生素治疗无效。因此，迫切需要通过新方法来克服耐药性或恢复抗生素的活性。针对假单胞菌喹诺酮信号定点感应（PQS-QS）系统是一种在不影响PA致病性的情况下消除PA致病性的有趣策略。在这里，我们报告2-磺酰基嘧啶的结构-活性关系，后者先前被确定为PQS受体PqsR和PQS合酶PqsD的双靶标抑制剂。SAR的阐明是通过使用配体效率和配体亲脂性效率的组合方法来选择最有前途的化合物。此外，使用Hansch分析在QSAR的指导下合理地修饰了最有效的抑制剂。最后，这些抑制剂显示出减少生物膜质量和细胞外DNA的能力，这是决定抗生素耐药性的重要因素。
• [EN] COMPOUNDS FOR THE TREATMENT OF HIV<br/>[FR] COMPOSÉS POUR TRAITER LE VIH
  申请人：GILEAD SCIENCES INC

  公开号：WO2013006738A1

  公开（公告）日：2013-01-10

  The invention provides compounds of formula (I): or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula (I), processes for preparing compounds of formula (I), intermediates useful for preparing compounds of formula I and therapeutic methods for treating a Retroviridae viral infection including an infection caused by the HIV virus.

  本发明提供了如下式（I）的化合物或其盐，还提供了包含如下式（I）化合物的药物组合物，制备如下式（I）化合物的方法，用于制备如下式（I）化合物的中间体以及治疗Retroviridae病毒感染的治疗方法，包括由HIV病毒引起的感染。
• [EN] SERINE/THREONINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA SÉRINE / THRÉONINE KINASE
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2013130976A1

  公开（公告）日：2013-09-06

  Compounds of Formula I or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof are provided, which are useful for the treatment of hyperproliferative, pain and inflammatory diseases. Methods of using compounds of Formula I or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

  提供了公式I或其立体异构体、互变异构体、前药或药用盐，这些化合物可用于治疗高增殖、疼痛和炎症性疾病。公开了使用公式I或其立体异构体、互变异构体、前药或药用盐在哺乳动物细胞中进行体外、体内和体内诊断、预防或治疗这些疾病或相关病理状况的方法。
• [EN] COMBINATION OF A MEK INHIBITOR AND AN ERK INHIBITOR FOR USE IN TREATMENT OF HYPERPROLIFERATIVE DISEASES<br/>[FR] COMBINAISON D'UN INHIBITEUR DE MEK ET D'UN INHIBITEUR D'ERK POUR L'UTILISATION DANS LE TRAITEMENT DE MALADIES HYPERPROLIFÉRATIVES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015032840A1

  公开（公告）日：2015-03-12

  The invention provides combinations comprising a MEK inhibitor (such as GDC-0973 or GDC-0623), or a pharmaceutically acceptable salt thereof and an ERK inhibitor (such as GDC-0994). The combinations are particularly useful for treating hyperproliferative disorders, such as cancer.

  该发明提供了包含MEK抑制剂（如GDC-0973或GDC-0623）或其药用盐以及ERK抑制剂（如GDC-0994）的组合物。这些组合物特别适用于治疗过度增殖性疾病，如癌症。