4-氯-5-甲氧基嘧啶-2-胺 | 4763-36-4

• 物质功能分类: 医药中间体 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4-氯-5-甲氧基嘧啶-2-胺
• 英文名称: 4-chloro-5-methoxypyrimidin-2-amine
• CAS: 4763-36-4
• 化学式: C₅H₆ClN₃O
• mdl: MFCD09027686
• 分子量: 159.575
• InChiKey: OXAYXWLBMCQAJC-UHFFFAOYSA-N

物化性质

• 熔点：
  146-148 °C(Solv: water, 20% (7732-18-5); acetic acid (64-19-7); ethanol (64-17-5))
• 沸点：
  345.3±45.0 °C(Predicted)
• 密度：
  1.398±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  10
• 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：
  61
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933599090
• 储存条件：
  -20°C

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4-Chloro-5-methoxypyrimidin-2-amine
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: 4-Chloro-5-methoxypyrimidin-2-amine
CAS number: 4763-36-4

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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.
Store in closed vessels, refrigerated.
Storage:

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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
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C5H6ClN3O
Molecular weight: 159.6

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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 chloride.

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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
Non-harzardous for air and ground transportation.

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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：

  4-氯-5-甲氧基嘧啶-2-胺 在 四(三苯基膦)钯 、 sodium hydride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 sodium iodide 、 锌 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 36.5h， 生成 rac-1-(1-(2-amino-5-methoxypyrimidin-4-yl)-1H-pyrrolo[3,2-c]-pyridin-6-yl)-3-methylpent-1-yn-3-ol trifluoroacetic acid salt
  参考文献：
  名称：

  发现能降低体内Tau磷酸化的强效和脑渗透性Tau Tubulin Kinase 1（TTBK1）抑制剂

  摘要：

  对与TTBK1激酶结构域结合的已知NIK抑制剂3的结构分析导致设计和合成了新型的氮杂吲唑TTBK1抑制剂，示例为8（细胞IC 50：571 nM）。通过对该系列类似物的系统优化，发现了31种有效的（细胞IC 50：315 nM）和具有适当CNS渗透性的选择性TTBK抑制剂（大鼠K p，uu：0.32），用于体内药理学研究。31的能力 在小鼠体温过低和大鼠发育模型中均证实了在疾病相关的Ser 422表位抑制tau磷酸化的作用，并提供了证明这一靶点的调节可能与阿尔茨海默氏病和其他疾病有关。

  DOI：

  10.1021/acs.jmedchem.1c00382

文献信息

• [EN] COMPLEMENT MODULATORS AND RELATED METHODS<br/>[FR] MODULATEURS DU COMPLÉMENT ET PROCÉDÉS ASSOCIÉS
  申请人：RA PHARMACEUTICALS INC

  公开号：WO2020205501A1

  公开（公告）日：2020-10-08

  The present disclosure presents compounds and compositions that interact with complement components. Some compounds inhibit complement activity. Included are small molecule compounds and compositions that function as C5 inhibitor compounds. Methods for inhibiting complement activity and methods of treating complement-related indications with the C5 inhibitor compounds and compositions are provided.

  本公开涉及与补体成分相互作用的化合物和组合物。一些化合物抑制补体活性。包括作为C5抑制剂化合物的小分子化合物和组合物。提供了抑制补体活性的方法以及利用C5抑制剂化合物和组合物治疗与补体相关症状的方法。
• [EN] 3-(2-AMINOPYRIMIDIN-4-YL)-5-(3-HYDROXYPROPYNYL)-1H-PYRROLO[2,3-C]PYRIDINE DERIVATIVES AS NIK INHIBITORS FOR THE TREATMENT OF CANCER<br/>[FR] DÉRIVÉS DE 3-(2-AMINOPYRIMIDIN-4-YL)-5-(3-HYDROXYPROPYNYL)-1H-PYRROLO[2,3-C]PYRIDINE EN TANT QU'INHIBITEURS DE NIK DANS LE TRAITEMENT DU CANCER
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2014174021A1

  公开（公告）日：2014-10-30

  The present invention relates to compounds of formula (I) which are inhibitors of NF-KB-inducing kinase (NIK - also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.

  本发明涉及式(I)化合物，该化合物是NF-KB诱导激酶（NIK，也称为MAP3K14）的抑制剂，用于治疗癌症、炎症性疾病、代谢性疾病和自身免疫性疾病。本发明还涉及包含这种化合物的药物组合物，制备这种化合物和组合物的方法，以及使用这种化合物或药物组合物预防或治疗癌症、炎症性疾病、包括肥胖和糖尿病的代谢性疾病和自身免疫性疾病。
• Discovery and Characterization of Selective and Ligand-Efficient DYRK Inhibitors
  作者：Scott H. Henderson、Fiona Sorrell、James Bennett、Oleg Fedorov、Marcus T. Hanley、Paulo H. Godoi、Roberta Ruela de Sousa、Sean Robinson、Alexander Ashall-Kelly、Iva Hopkins Navratilova、Daryl S. Walter、Jonathan M. Elkins、Simon E. Ward

  DOI：10.1021/acs.jmedchem.1c01115

  日期：2021.8.12

  pyrazolo[1,5-b]pyridazine inhibitors with excellent ligand efficiencies, good physicochemical properties, and a high degree of selectivity over the kinome. Compound 11 exhibited good permeability and cellular activity without P-glycoprotein liability, extending the utility of 11 in an in vivo setting. These pyrazolo[1,5-b]pyridazines are a viable lead series in the discovery of new therapies for the

  双特异性酪氨酸调节激酶​​ 1A (DYRK1A) 调节大脑发育过程中神经元祖细胞的增殖和分化。因此，DYRK1A 作为治疗神经退行性疾病（包括阿尔茨海默病（AD）和唐氏综合症）的靶标引起了人们的兴趣。最近，DYRK1A 的抑制已被研究为糖尿病的潜在治疗方法，而 DYRK1A 作为细胞周期介质的作用引起了人们对肿瘤适应症的兴趣。构效关系（SAR）分析与高分辨率X射线晶体学相结合，产生了一系列吡唑并[1,5- b ]哒嗪抑制剂，具有优异的配体效率、良好的理化性质以及对其他药物的高度选择性。激酶。化合物11表现出良好的渗透性和细胞活性，且无需 P-糖蛋白，从而扩展了11在体内环境中的效用。这些吡唑并[1,5- b ]哒嗪是发现治疗与 DYRK1A 功能相关疾病的新疗法的可行的先导系列。
• Identification of potent and selective MTH1 inhibitors
  作者：Alessia Petrocchi、Elisabetta Leo、Naphtali J. Reyna、Matthew M. Hamilton、Xi Shi、Connor A. Parker、Faika Mseeh、Jennifer P. Bardenhagen、Paul Leonard、Jason B. Cross、Sha Huang、Yongying Jiang、Mario Cardozo、Giulio Draetta、Joseph R. Marszalek、Carlo Toniatti、Philip Jones、Richard T. Lewis

  DOI：10.1016/j.bmcl.2016.02.026

  日期：2016.3

  Structure based design of a novel class of aminopyrimidine MTH1 (MutT homolog 1) inhibitors is described. Optimization led to identification of IACS-4759 (compound 5), a sub-nanomolar inhibitor of MTH1 with excellent cell permeability and good metabolic stability in microsomes. This compound robustly inhibited MTH1 activity in cells and proved to be an excellent tool for interrogation of the utility

  描述了基于结构的新型氨基嘧啶MTH1（MutT同系物1）抑制剂的设计。优化导致鉴定IACS-4759（化合物5），MTH1亚纳摩尔抑制剂，在微粒体中具有出色的细胞通透性和良好的代谢稳定性。该化合物强烈抑制细胞中的MTH1活性，并被证明是在肿瘤学背景下研究MTH1抑制作用的极佳工具。
• PYRIMIDINE DERIVATIVES FOR THE TREATMENT OF VIRAL INFECTIONS
  申请人：McGowan David

  公开号：US20140045849A1

  公开（公告）日：2014-02-13

  This invention relates to pyrimidine derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections such as HCV or HBV.

  这项发明涉及嘧啶衍生物，其制备方法，药物组成，以及它们在治疗病毒感染如HCV或HBV中的应用。