3-氨基-4-溴-6-氯哒嗪 | 446273-59-2

• 物质功能分类: 医药中间体 - 杂环化合物 - 哒嗪类化合物
• 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: 3-氨基-4-溴-6-氯哒嗪
• 中文别名: 6-氯-4-溴-3-氨基哒嗪；3-氨基-4-溴-6-氯吡嗪；4-溴-5-氯-3-氨基哒嗪
• 英文名称: 4-bromo-6-chloro-3-pyridazineamine
• 英文别名: 4-bromo-6-chloropyridazin-3-amine；3-amino-4-bromo-6-chloropyridazine；(4-bromo-6-chloropyridazin-3-yl)amine；4-bromo-6-chloropyridazine-3-amine
• CAS: 446273-59-2
• 化学式: C₄H₃BrClN₃
• 分子量: 208.445
• InChiKey: FGOWNGCSUSKHQI-UHFFFAOYSA-N

物化性质

• 沸点：
  385.4±37.0 °C(Predicted)
• 密度：
  1.960
• pKa：
  1.93±0.10 (Predicted,Most Basic Temp: 25 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险品标志：
  T
• 安全说明：
  S45
• 危险类别码：
  R25
• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 3-Amino-4-bromo-6-chloropyridazine
Synonyms: 4-Bromo-6-chloropyridazin-3-amine

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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: 3-Amino-4-bromo-6-chloropyridazine
CAS number: 446273-59-2

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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.
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.

---

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: C4H3BrClN3
Molecular weight: 208.4

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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, hydrogen bromide.

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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

制备方法与用途

用途

3-氨基-4-溴-6-氯哒嗪是一种用于制备新型高效咪唑并[1,2-b]哒嗪PDE10A抑制剂的化合物。

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
  3-氨基-6-氯哒嗪	3-Amino-6-chloropyridazine	5469-69-2	C4H4ClN3	129.549

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  5-溴-3-氯吡嗪	5-bromo-3-chloropyridazine	1196155-33-5	C4H2BrClN2	193.43

反应信息

• 作为反应物：
  描述：

  3-氨基-4-溴-6-氯哒嗪 在 硫酸 、 溶剂黄146 、 sodium nitrite 作用下， 以 水 为溶剂， 生成 4-溴-6-氯吡嗪-3(2H)-酮
  参考文献：
  名称：

  PI3K/HDAC双重抑制剂新型吡嗪酮衍生物的设计、合成及生物学评价

  摘要：

  PI3Ks和HDACs在白血病的发生和发展中起着重要作用。在此，基于支架置换和杂合策略，合理设计和合成了一系列新型吡嗪-2(1 H )-酮衍生物作为新型双重 PI3K 和 HDAC 抑制剂。大多数目标化合物对 PI3Kα 和 HDAC6 显示出强大的抑制效力。特别是，化合物9q对 PI3Kα 和 HDAC6 具有抑制作用，IC 50值为 372 nM 和 4.5 nM，对 MV4-11 细胞具有抗增殖活性，IC 50值为 0.093 ± 0.012 μM。进一步的机理研究表明9q诱导细胞凋亡，使细胞周期停滞在G2/M期，促进α-微管蛋白的乙酰化，阻断MV4-11细胞中的PI3K/AKT/mTOR信号通路。所有结果表明，9q是进一步开发用于白血病治疗的新型 PI3K/HDAC 双重抑制剂的有前途的主要候选者。

  DOI：

  10.1016/j.bmc.2022.117067
• 作为产物：
  描述：

  3-氨基-6-氯哒嗪 在 溴 、 碳酸氢钠 作用下， 以 甲醇 为溶剂， 反应 20.0h， 以37%的产率得到3-氨基-4-溴-6-氯哒嗪
  参考文献：
  名称：

  设计和评估作为钙动员拮抗剂的杂二价PAR1-PAR2配体。

  摘要：

  基于已报道的针对亚型PAR1和PAR2的拮抗剂，已经制备了靶向推定的蛋白酶激活受体（PAR）异聚体的新型二价配体。包含炔连接体的PAR1拮抗剂RWJ-58259的改良版通过环加成反应与连接至基于咪唑并哒嗪的PAR2拮抗剂的叠氮基封端的聚乙二醇（PEG）间隔基连接。对PAR1-PAR2拮抗剂的初步研究表明，它们在PAR1和PAR2激动剂驱动的内皮细胞和癌细胞中抑制Gαq介导的钙动员。这种新型化合物有望预防再狭窄，癌细胞转移和其他增生性疾病。

  DOI：

  10.1021/acsmedchemlett.8b00538
• 作为试剂：
  描述：

  1-(2,6-二氯-3-氟苯基)乙醇 、 3-氨基-4-溴-6-氯哒嗪 在 3-氨基-4-溴-6-氯哒嗪 作用下， 以37.7的产率得到(R)-6-Chloro-4-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridazin-3-amine
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRIDAZINE CARBOXAMIDE COMPOUNDS AS KINASE INHIBITOR COMPOUNDS
  [FR] COMPOSÉS SUBSTITUÉS DE PYRIDAZINE CARBOXAMIDE EN TANT QUE COMPOSÉS INHIBITEURS DE KINASE

  摘要：

  新的吡啶嗪衍生物具有意外的药物特性，作为蛋白激酶抑制剂，特别是对c-Met的抑制作用，在治疗与异常蛋白激酶活性相关的疾病，如癌症方面具有用途。

  公开号：

  WO2012048258A2

文献信息

• [EN] SUBSTITUTED PYRIDAZINE CARBOXAMIDE COMPOUNDS AS KINASE INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS DE PYRIDAZINECARBOXAMIDE SUBSTITUÉS UTILES EN TANT QUE COMPOSÉS INHIBITEURS DE KINASE
  申请人：XCOVERY INC

  公开号：WO2009154769A1

  公开（公告）日：2009-12-23

  Pyridazine derivatives have unexpected drug properties as inhibitors of protein kinases and are useful in treating disorders related to abnormal protein kinase activities such as cancer.

  吡啶并呋嗪衍生物作为蛋白激酶抑制剂具有意想不到的药物特性，并可用于治疗与异常蛋白激酶活性相关的疾病，如癌症。
• BRM TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas Operations, Inc.

  公开号：US20190300521A1

  公开（公告）日：2019-10-03

  The present disclosure relates to bifunctional compounds, which find utility as modulators of SMARCA2 or BRM (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand that binds to the Von Hippel-Lindau E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，其作为SMARCA2或BRM（靶蛋白）的调节剂具有实用性。具体而言，本公开涉及包含一端结合Von Hippel-Lindau E3泛素连接酶的配体，另一端结合靶蛋白的双功能化合物，使得靶蛋白与泛素连接酶靠近以实现靶蛋白的降解（和抑制）。本公开展示了与靶蛋白降解/抑制相关的广泛药理活性。本公开的化合物和组合物用于治疗或预防由靶蛋白聚集或积累导致的疾病或紊乱。
• IMIDAZO[1,2-b]PYRIDAZINE DERIVATIVES AND THEIR USE AS PDE10 INHIBITORS
  申请人：Pastor-Fernández Joaquin

  公开号：US20110269752A1

  公开（公告）日：2011-11-03

  The present invention relates to novel imidazo[1,2- b ]pyridazine derivatives which are inhibitors of the phosphodiesterase 10 enzyme (PDE10) and which are useful for the treatment or prevention of neurological, psychiatric and metabolic disorders in which the PDE10 enzyme is involved. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, to the use of such compounds or pharmaceutical compositions for the prevention or treatment of neurological, psychiatric and metabolic disorders and diseases.

  本发明涉及新型咪唑并[1,2-b]吡啶嗪衍生物，其为磷酸二酯酶10（PDE10）的抑制剂，并且适用于治疗或预防涉及PDE10酶的神经、精神和代谢紊乱。该发明还涉及包含这种化合物的药物组合物，用于制备这种化合物和组合物的方法，以及利用这种化合物或药物组合物预防或治疗神经、精神和代谢紊乱和疾病。
• [EN] TRPV4 ANTAGONISTS<br/>[FR] ANTAGONISTES DE TRPV4
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2013012500A1

  公开（公告）日：2013-01-24

  The present invention relates to spirocarbamate compounds of Formula (I) in which R1, (R2)Y, R3, R4, X and A have the meanings given in the specification. The invention further provides pharmaceutical compositions containing the compounds or pharmaceutically acceptable salts thereof and relates to their use of these compounds as TRPV4 antagonists in treating or preventing conditions associated with TRPV4 imbalance.

  本发明涉及式（I）中的螺环氨基甲酸酯化合物，其中R1，（R2）Y，R3，R4，X和A具有规范中给定的含义。该发明还提供含有这些化合物或其药用可接受盐的药物组合物，并涉及将这些化合物用作TRPV4拮抗剂以治疗或预防与TRPV4失衡相关的疾病。
• [EN] BIARYL KINASE INHIBITORS<br/>[FR] INHIBITEURS BIARYLES DE KINASES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2017059080A1

  公开（公告）日：2017-04-06

  The present disclosure is directed to biaryl compounds of formula (I) which can inhibit AAKl (adaptor associated kinase 1), compositions comprising such compounds and their use for treating e.g. pain, Alzheimer's disease, Parkinson's disease and schizophrenia.

  本公开涉及公式（I）的联苯化合物，可以抑制AAK1（适配器相关激酶1），包括这种化合物的组合物以及它们用于治疗疼痛、阿尔茨海默病、帕金森病和精神分裂症等的用途。