6-氯吡啶并[3,2-d]嘧啶-4(1H)-酮 | 171178-33-9

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 中文名称: 6-氯吡啶并[3,2-d]嘧啶-4(1H)-酮
• 中文别名: 无
• 英文名称: 6-chloropyrido[3,2-d]pyrimidin-4(3H)-one
• 英文别名: 6-chloro-3H-pyrido[3,2-d]pyrimidin-4-one；6-Chloropyrido[3,2-d]pyrimidin-4(3H)-one
• CAS: 171178-33-9
• 化学式: C₇H₄ClN₃O
• mdl: MFCD11846203
• 分子量: 181.581
• InChiKey: YAALXPGJSHTRFX-UHFFFAOYSA-N

物化性质

• 沸点：
  400.8±55.0 °C(Predicted)
• 密度：
  1.66

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 6-Chloropyrido[3,2-d]pyrimidin-4(3h)-one
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: 6-Chloropyrido[3,2-d]pyrimidin-4(3h)-one
CAS number: 171178-33-9

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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: C7H4ClN3O
Molecular weight: 181.6

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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：

  6-氯吡啶并[3,2-d]嘧啶-4(1H)-酮 在 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以80 %的产率得到4,6-二氯-吡啶并[3,2-d]嘧啶
  参考文献：
  名称：

  Mnk1/2抑制剂4-(吲哚啉-1-基)-6-取代-吡啶并[3,2-d]嘧啶衍生物的设计、合成和生物学评价

  摘要：

  Mnk-eIF4E 轴在肿瘤发展中起着至关重要的作用，抑制 Mnk 激酶是一种有前景的癌症治疗方法。从片段开始，设计并合成了一系列4-(二氢吲哚-1-基)-6-取代-吡啶并[3,2-]嘧啶衍生物。在这些衍生物中，化合物对 Mnk1 和 Mnk2 显示出最高的效力，IC 值分别为 0.8 和 1.5 nM。此外，它在 30 种选定的激酶中表现出良好的选择性。显着抑制 MOLM-13 和 K562 细胞系生长并导致细胞周期停滞。此外，Western blot 检测显示，有效下调下游蛋白 -eIF4E、Mcl-1 和 c-myc。此外，在大鼠血浆以及大鼠和人类微粒体中表现出显着的稳定性。抗肿瘤活性研究表明，在 LL/2 同基因模型中，治疗可抑制肿瘤生长。这些发现凸显了 Mnks 作为新型有效抑制剂的潜力，值得进一步研究。

  DOI：

  10.1016/j.ejmech.2024.116499
• 作为产物：
  描述：

  6-氯-2-氰基-3-硝基吡啶 在 palladium on activated charcoal 硫酸 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 70.0 ℃ 、413.69 kPa 条件下， 反应 21.5h， 生成 6-氯吡啶并[3,2-d]嘧啶-4(1H)-酮
  参考文献：
  名称：

  酪氨酸激酶抑制剂。10.异构体4-[（（3-溴苯基）氨基]吡啶并[d]-嘧啶是表皮生长因子受体的酪氨酸激酶功能的有效ATP结合位点抑制剂。

  摘要：

  在发现4-[（3-溴苯基）氨基]-喹唑啉具有极高的抑制表皮生长因子受体（EGFR）酪氨酸激酶活性的能力（例如3，IC50为0.029 nM）之后，合成并评估了在6或7位带有供电子基团的相关吡啶并[d]嘧啶。通过亲核取代相应的6-和7-氟类似物来制备化合物。尽管所有系列成员均显示出对分离的EGFR的有效抑制活性，但不同的异构吡啶并[d]嘧啶与母体喹唑啉之间存在重要差异。总的来说，[3,4-d]和[4,3-d]系列是最有效的，其次是[3,2-d]化合物，[2,3-d]类似物的活性最低。在母体喹唑啉系列中，向6-或7-NH2取代基（即NHMe和NMe2基团）中增加空间位阻会显着降低效能，而在[3,2-d]系列中则没有这种趋势。此外，在7-取代的吡啶并[4,3-d]-和6-取代的吡啶并[3,4-d]嘧啶系列中，并且在有限的程度上在7-取代的吡啶并[2,3-d]系列中，这样的取代作用显着提高了效力，其程度为7-（甲基氨基）吡啶并[4

  DOI：

  10.1021/jm9508651

文献信息

• ION CHANNEL INHIBITOR COMPOUNDS FOR CANCER TREATMENT
  申请人：Centre National de la Recherche Scientifique

  公开号：US20210009581A1

  公开（公告）日：2021-01-14

  The present invention concerns a compound of following general formula (I): where: either R is an R 1 group and R′ is an -A 1 -Cy 1 group, or R is an -A 1 -Cy 1 group and R′ is an R 1 group, R 1 particularly being H or (C 1 -C 6 )alkyl group; A 1 being an —NH— radical or —NH—CH 2 — radical; Cy 1 particularly being a phenyl group, A is a fused (hetero)aromatic ring having 5 to 7 atoms, for use for treating cancer.

  本发明涉及以下一般式（I）的化合物： 其中： R是R1基团且R′是-A1-Cy1基团，或者R是-A1-Cy1基团且R′是R1基团， 其中R1特别是H或（C1-C6）烷基基团； A1是—NH—基团或—NH—CH2—基团； Cy1特别是苯基， A是具有5到7个原子的融合（杂）芳香环， 用于治疗癌症。
• [EN] OXADIAZOLONES AS TRANSIENT RECEPTOR POTENTIAL CHANNEL INHIBITORS<br/>[FR] OXADIAZOLONES EN TANT QU'INHIBITEURS DE CANAL POTENTIEL RÉCEPTEUR TRANSITOIRE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2018096159A1

  公开（公告）日：2018-05-31

  The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.

  该发明涉及式(I)的化合物及其药用可接受的盐。此外，本发明涉及制备方法和使用式(I)的化合物的方法，以及含有这种化合物的药物组合物。这些化合物可能在治疗由TRPA1介导的疾病和症状，如疼痛方面有用。
• [EN] SMALL MOLECULE INHIBITORS OF NF-kB INDUCING KINASE<br/>[FR] INHIBITEURS À PETITE MOLÉCULE DE KINASE INDUISANT NF-KB
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2020239999A1

  公开（公告）日：2020-12-03

  The present invention relates to compounds that inhibit NIK and pharmaceutical compositions comprising such compounds and methods of using the same. These compounds and pharmaceutical compositions are envisaged to be useful for preventing or treating diseases such as cancer (such as B-cell malignancies including leukemias, lymphomas and myeloma), inflammatory disorders, autoimmune disorders, immunodermatologic disorders such as palmoplantar pustulosis and hidradenitis suppurativa, and metabolic disorders such as obesity and diabetes.

  本发明涉及抑制NIK的化合物，以及包含这些化合物的药物组合物和使用方法。这些化合物和药物组合物预期能用于预防或治疗癌症（如包括白血病、淋巴瘤和多发性骨髓瘤的B细胞恶性肿瘤）、炎症性疾病、自身免疫疾病、免疫皮肤病学疾病（如掌跖脓疱病和化脓性汗腺炎）以及代谢紊乱疾病（如肥胖和糖尿病）。
• [EN] NEW PIPERIDINYL DERIVATIVES, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM<br/>[FR] NOUVEAUX DÉRIVÉS DE PIPÉRIDINYLE, PROCÉDÉ DE PRÉPARATION DE CEUX-CI ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT
  申请人：SERVIER LAB

  公开号：WO2017212012A1

  公开（公告）日：2017-12-14

  Compounds of formula (I) wherein R1, R2, R3, n and W are as defined in the description. Medicaments.

  式（I）中R1、R2、R3、n和W的化合物如描述中所定义。药物。
• Discovery of Selective 4-Amino-pyridopyrimidine Inhibitors of MAP4K4 Using Fragment-Based Lead Identification and Optimization
  作者：Terry D. Crawford、Chudi O. Ndubaku、Huifen Chen、Jason W. Boggs、Brandon J. Bravo、Kelly DeLaTorre、Anthony M. Giannetti、Stephen E. Gould、Seth F. Harris、Steven R. Magnuson、Erin McNamara、Lesley J. Murray、Jim Nonomiya、Amy Sambrone、Stephen Schmidt、Tanya Smyczek、Mark Stanley、Philip Vitorino、Lan Wang、Kristina West、Ping Wu、Weilan Ye

  DOI：10.1021/jm500155b

  日期：2014.4.24

  implicated in the regulation of many biological processes. A fragment-based lead discovery approach was used to generate potent and selective MAP4K4 inhibitors. The fragment hit pursued in this article had excellent ligand efficiency (LE), an important attribute for subsequent successful optimization into drug-like lead compounds. The optimization efforts eventually led us to focus on the pyridopyrimidine

  丝裂原活化的蛋白激酶激酶激酶激酶4（MAP4K4）是一种丝氨酸/苏氨酸激酶，与许多生物过程的调控有关。基于片段的线索发现方法用于生成有效的和选择性的MAP4K4抑制剂。本文追求的碎片命中具有出色的配体效率（LE），这是随后成功优化成药物样先导化合物的重要属性。优化工作最终使我们专注于吡啶并嘧啶系列，从中鉴定出6-（2-氟吡啶-4-基）吡啶[3,2 - d ]嘧啶-4-胺（29）。该化合物具有低纳摩尔浓度，优异的激酶选择性和良好的体内暴露，并且在人肿瘤异种移植模型中显示出体内药效学作用。