4-氨基-5,6-二氯嘧啶 | 310400-38-5

• 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 - 有机杂环化合物 - 二嗪类
• 中文名称: 4-氨基-5,6-二氯嘧啶
• 中文别名: 5,6-二氯嘧啶-4-胺
• 英文名称: 5,6-dichloropyrimidin-4-amine
• 英文别名: 4-amino-5,6-dichloropyrimidine；5,6-dichloro-pyrimidin-4-ylamine
• CAS: 310400-38-5
• 化学式: C₄H₃Cl₂N₃
• mdl: MFCD09837293
• 分子量: 163.994
• InChiKey: ISTJUVRUUBNZNB-UHFFFAOYSA-N

物化性质

• 熔点：
  214 - 216°C
• 沸点：
  301.8±37.0 °C(Predicted)
• 密度：
  1.606
• 溶解度：
  DMSO（少量）、甲醇（少量）

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 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

• 安全说明：
  S26,S39
• 危险类别码：
  R41
• 海关编码：
  2933599090
• 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: 5,6-Dichloropyrimidin-4-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: 5,6-Dichloropyrimidin-4-amine
CAS number: 310400-38-5

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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.

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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: C4H3Cl2N3
Molecular weight: 164.0

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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：

  3-氨基苯酚 、 4-氨基-5,6-二氯嘧啶 在 caesium carbonate 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 1.0h， 生成 (6-(3-aminophenoxy)-5-chloropyrimidin-4-amine)
  参考文献：
  名称：

  Evobrutinib的发现：一种口服，有效且高选择性的共价Bruton酪氨酸激酶（BTK）抑制剂，可用于治疗免疫性疾病。

  摘要：

  Bruton的酪氨酸激酶（BTK）抑制剂如ibrutinib在B细胞恶性肿瘤的治疗中起着重要作用。但是，此类药物需要进一步改进，特别是在不良事件（可能由激酶混杂引起的不良事件）方面，这使其无法在非肿瘤适应症中进行评估。在这里，我们报告evobrutinib的发现和临床前表征，evobrutinib是一种具有高激酶选择性的有效的专性共价抑制剂。Evobrutinib表现出足够的临床前药代动力学和药效动力学特征，可在功效模型中进行体内评估。此外，依武鲁替尼对BTK的选择性高于表皮生长因子受体和其他Tec家族激酶，这表明脱靶相关不良反应的可能性较低。

  DOI：

  10.1021/acs.jmedchem.9b00794
• 作为产物：
  描述：

  4,5,6-三氯嘧啶 在 氨 作用下， 以55%的产率得到4-氨基-5,6-二氯嘧啶
  参考文献：
  名称：

  Makosza; Ostrowski, Polish Journal of Chemistry, 2000, vol. 74, # 10, p. 1355 - 1361

  摘要：

  DOI：

文献信息

• [EN] BRUTON'S TYROSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE TYROSINE KINASE DE BRUTON
  申请人：BIOGEN IDEC INC

  公开号：WO2011029046A1

  公开（公告）日：2011-03-10

  The present invention provides compounds useful as inhibitors of Btk, compositions thereof, and methods of using the same.

  本发明提供了用作Btk抑制剂的化合物、其组合物以及使用方法。
• 一种用于治疗癌症的炔类杂环化合物及其制备方法与用途
  申请人：药雅科技（上海）有限公司

  公开号：CN112851587A

  公开（公告）日：2021-05-28

  本发明公开一种FGFR蛋白酪氨酸激酶的临床突变体的选择性抑制剂，及具有通式(I)所示的化合物及其可药用的盐，含有所述化合物和/或其药用的盐的药物组合物、应用所述化合物或可药用的盐治疗或者预防FGFR激酶相关性病症、特别是肿瘤的药物中的用途，这是一类含有炔类杂环模板化合物，同时公开了该类化合物的或其可药用的盐的药物组合物的制备方法。
• Structure-based Design of Pyridone–Aminal eFT508 Targeting Dysregulated Translation by Selective Mitogen-activated Protein Kinase Interacting Kinases 1 and 2 (MNK1/2) Inhibition
  作者：Siegfried H. Reich、Paul A. Sprengeler、Gary G. Chiang、James R. Appleman、Joan Chen、Jeff Clarine、Boreth Eam、Justin T. Ernst、Qing Han、Vikas K. Goel、Edward Z. R. Han、Vera Huang、Ivy N. J. Hung、Adrianna Jemison、Katti A. Jessen、Jolene Molter、Douglas Murphy、Melissa Neal、Gregory S. Parker、Michael Shaghafi、Samuel Sperry、Jocelyn Staunton、Craig R. Stumpf、Peggy A. Thompson、Chinh Tran、Stephen E. Webber、Christopher J. Wegerski、Hong Zheng、Kevin R. Webster

  DOI：10.1021/acs.jmedchem.7b01795

  日期：2018.4.26

  Mitogen-activated protein kinase interacting kinases (MNK)1/2 are key regulators of mRNA translation integrating signals from oncogenic and immune signaling pathways through phosphorylation of eIF4E and other mRNA binding proteins. Modulation of these key effector proteins regulates mRNA, which controls tumor/stromal cell signaling. Compound 23 (eFT508), an exquisitely selective, potent dual MNK1/2 inhibitor, was

  mRNA的翻译失调在肿瘤发生中起主要作用。丝裂原激活的蛋白激酶相互作用激酶（MNK）1/2是mRNA翻译的关键调节因子，其通过eIF4E和其他mRNA结合蛋白的磷酸化整合来自致癌和免疫信号通路的信号。这些关键效应蛋白的调节可调节mRNA，从而控制肿瘤/基质细胞的信号传导。化合物23（eFT508）是一种选择性强效的双重MNK1 / 2抑制剂，设计用于评估在mRNA翻译水平上控制癌基因信号传导的潜力。晶体结构指导的设计利用了MNK特有的立体电子相互作用，最终形成了激酶文献中首次描述的新型吡啶酮-氨基结构。化合物23在弥漫性大细胞B细胞淋巴瘤和实体瘤模型中具有强效的体内抗肿瘤活性，这表明控制翻译失调具有真正的治疗潜力。化合物23目前正在实体瘤和淋巴瘤的2期临床试验中进行评估。化合物23是第一种高度选择性的双重MNK抑制剂，可靶向靶向翻译失调的临床药物。
• [EN] TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF<br/>[FR] INHIBITEURS DE LA KINASE TRKA, COMPOSITIONS ET PROCÉDÉS ASSOCIÉS
  申请人：MERCK SHARP & DOHME

  公开号：WO2016161572A1

  公开（公告）日：2016-10-13

  The present invention is directed to bicyclic heteroaryl benzamide compounds of formulas (I) which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence are useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.

  本发明涉及式(I)所示的二环杂芳基苯甲酰胺化合物，该化合物是肌动蛋白相关激酶（Trk）家族蛋白激酶抑制剂，因此可用于治疗疼痛、炎症、癌症、再狭窄、动脉粥样硬化、银屑病、血栓形成、与髓鞘形成不良或脱髓鞘相关的疾病、障碍、损伤或功能障碍，或与神经生长因子（NGF）受体TrkA的异常活性相关的疾病或障碍。
• Discovery of 4-aminopyrimidine analogs as highly potent dual P70S6K/Akt inhibitors
  作者：Yufang Xiao、Bayard R. Huck、Ruoxi Lan、Lizbeth DeSelm、Xiaoling Chen、Hui Qiu、Constantin Neagu、Theresa Johnson、Igor Mochalkin、Anna Gardberg、Xuliang Jiang、Hui Tian、Vikram Dutt、Dusica Santos、Jared Head、Jennifer Jackson、Sakeena Syed、Jing Lin、Erik Wilker、Jianguo Ma、Anderson Clark、Andreas Machl、Donald Bankston、Christopher C.V. Jones、Andreas Goutopoulos、Brian Sherer

  DOI：10.1016/j.bmcl.2021.128352

  日期：2021.10

  PI3K/Akt/mTOR kinase pathway is associated with human cancers. A dual p70S6K/Akt inhibitor is sufficient to inhibit strong tumor growth and to block negative impact of the compensatory Akt feedback loop activation. A scaffold docking strategy based on an existing quinazoline carboxamide series identified 4-aminopyrimidine analog 6, which showed a single-digit nanomolar and a micromolar potencies in p70S6K

  PI3K/Akt/mTOR 激酶通路的激活与人类癌症有关。双重 p70S6K/Akt 抑制剂足以抑制强烈的肿瘤生长并阻止补偿性 Akt 反馈回路激活的负面影响。基于现有喹唑啉甲酰胺系列的支架对接策略确定了 4-氨基嘧啶类似物6，其在 p70S6K 和 Akt 酶测定中显示出个位数的纳摩尔和微摩尔效力。SAR 优化提高了 Akt 酶和 p70S6K 细胞的效力，降低了 hERG 的敏感性，并最终发现了有希望的候选者37，它在 p70S6K 和 Akt 生化分析中都表现出个位数的纳摩尔值，以及 hERG 活性（IC 50 = 17.4 微米）。该药物在抑制小鼠乳腺癌肿瘤生长方面表现出剂量依赖性功效，并且在 200 mg/kg po 的剂量下长达 24 小时覆盖超过 90% 的 pS6 抑制。