4-chloro-N-cyclohexylpicolinamide | 1094332-66-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-chloro-N-cyclohexylpicolinamide
• 英文别名: N-cyclohexyl-4-chloro-2-pyridinecarboxamide；4-chloro-N-cyclohexylpyridine-2-carboxamide；N-Cyclohexyl 4-chloropicolinamide
• CAS: 1094332-66-7
• 化学式: C₁₂H₁₅ClN₂O
• 分子量: 238.717
• InChiKey: NXWNXOZYZLEOGK-UHFFFAOYSA-N

物化性质

• 沸点：
  399.5±27.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933399090

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: N-Cyclohexyl 4-chloropicolinamide
Synonyms: 4-Chloro-N-cyclohexylpyridine-2-carboxamide

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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: N-Cyclohexyl 4-chloropicolinamide
CAS number: 1094332-66-7

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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: C12H15ClN2O
Molecular weight: 238.7

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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-chloro-N-cyclohexylpicolinamide 在 potassium tert-butylate 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 4-(3-(3-(4-chloro-3-(trifluoromethyl)phenyl)thioureido)phenoxy)-N-cyclohexylpicolinamide
  参考文献：
  名称：

  Design, synthesis and biological activities of sorafenib derivatives as antitumor agents

  摘要：

  A series of novel sorafenib derivatives, 9a-w, was designed and synthesized in high yields using various substituted anilines, and their antiproliferative activities against HCT116, PC-3 and MDA-MB-231 cell lines were also evaluated and described. All compounds exhibited potent antiproliferative activity against HCT116 and PC-3 cells with IC50 = 2.8-52.0 and 2.2-45.6 mu M; compounds 9p and 9q demonstrated competitive antiproliferative activities to sorafenib against all three cancer cell lines, the cytotoxicity of compound 9r is more potent than that of sorafenib. Compounds (9g, 9p, 9q and 9r) were chosen for further evaluation of the anti-angiogenesis activity, and showed the inhibition of sprout formation from aortic ring ex vivo. The structures of all the newly synthesized compounds were determined by H-1 NMR, C-13 NMR and HRMS. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.031
• 作为产物：
  描述：

  4-氯-吡啶-2-酰氯 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 生成 4-chloro-N-cyclohexylpicolinamide
  参考文献：
  名称：

  含有索拉非尼类似物作为抗肿瘤剂的硫脲的设计，合成和生物学活性

  摘要：

  设计并合成了一系列新型的含有索拉非尼衍生物9a – t的二芳基硫脲。所有新合成的化合物的结构均通过1 H NMR，13 C NMR和HRMS确定。评估并描述了它们对HCT116和MDA-MB-231细胞系的抗增殖活性，以及​​对VEGFR磷酸化的抑制活性。一些化合物对细胞系和VEGFR均显示出显着活性。化合物9g，9m，9o和9p对参考标准索拉非尼具有竞争性抗增殖活性，而化合物9d，9m和9p显示出对VEGFR的磷酸化的显着抑制活性。

  DOI：

  10.1016/j.bmc.2012.03.018

文献信息

• New Sorafenib Derivatives: Synthesis, Antiproliferative Activity Against Tumour Cell Lines and Antimetabolic Evaluation
  作者：Željka Babić、Maja Crkvenčić、Zrinka Rajić、Ana-Matea Mikecin、Marijeta Kralj、Jan Balzarini、Mariya Petrova、Jos Vanderleyden、Branka Zorc

  DOI：10.3390/molecules17011124

  日期：——

  cytostatic activity against a panel of carcinoma, lymphoma and leukemia tumour cell lines. In addition, their antimetabolic potential was investigated as well. The most prominent antiproliferative activity was obtained for compounds 4a–e (IC50 = 1-4.3 μmol·L−1). Their potency was comparable to the potency of sorafenib, or even better. The compounds inhibited DNA, RNA and protein synthesis to a similar

  索拉非尼是一种相对较新的细胞抑制药物，被批准用于治疗肾细胞癌和肝细胞癌。在本报告中，我们描述了索拉非尼衍生物 4a-e 的合成，其在酰胺部分与索拉非尼不同。4 步合成途径包括制备 4-氯吡啶-2-碳酰氯盐酸盐 (1)、4-氯-吡啶-2-甲酰胺 2a-e、4-(4-氨基苯氧基)-吡啶-2-甲酰胺 3a- e 和目标化合物 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-phenoxy]-pyridine-2-carboxamides 4a–e。对所有化合物进行了全面的化学表征并评估了它们对一组癌、淋巴瘤和白血病肿瘤细胞系的细胞抑制活性。此外，还研究了它们的抗代谢潜力。化合物4a-e 获得了最突出的抗增殖活性（IC50 = 1-4.3 μmol·L-1）。它们的效力与索拉非尼的效力相当，甚至更好。这些化合物以相似的程度抑制 DNA、RNA
• Discovery of novel picolinamide-based derivatives as novel VEGFR-2 kinase inhibitors: synthesis,<i>in vitro</i>biological evaluation and molecular docking
  作者：Wuji Sun、Shubiao Fang、Hong Yan

  DOI：10.1039/c8md00057c

  日期：——

  Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in tumor angiogenesis, and inhibition of the VEGFR-2 signaling pathway has emerged as an attractive target for cancer therapy. In our effort, a novel series of picolinamide-based derivatives were designed and synthesized as potent and effective VEGFR-2 inhibitors. All the newly prepared compounds were evaluated in vitro for

  血管内皮生长因子受体2（VEGFR-2）在肿瘤血管生成中起着至关重要的作用，而对VEGFR-2信号通路的抑制已成为癌症治疗的诱人靶标。在我们的努力中，设计并合成了一系列新的基于吡啶啉酰胺的衍生物，它们是有效且有效的VEGFR-2抑制剂。在体外评估所有新制备的化合物对A549和HepG2细胞系的抗增殖活性。在新化合物中，8j和8l对A549和HepG2细胞系均表现出更好的活性。进行分子对接以研究与VEGFR-2（PDB代码：4ASD）的结合能力和结合方式。
• Thiourea and thioether derivatives of sorafenib: synthesis, crystal structure, and antiproliferative activity
  作者：Jianwen Yao、Jing Chen、Zuopeng He、Wei Sun、Hao Fang、Wenfang Xu

  DOI：10.1007/s00044-012-0400-8

  日期：2013.8

  A series of novel sorafenib derivatives containing diaryl thiourea and thioether, 9a-u, was designed and synthesized, and their antiproliferative activities against HCT116 and MDA-MB-231 cell lines were also evaluated and described. Most compounds exhibited potent antiproliferative activity against HCT116 cells with IC50 = 1.8-80.4 mu M. Compounds 9p, 9r, and 9s demonstrated competitive antiproliferative activities to sorafenib, against all two cancer cell lines. The structures of all the newly synthesized compounds were determined by H-1 NMR, C-13 NMR, and HRMS, and compound 9n was characterized by single-crystal X-ray diffraction. Primary structure-activity relationships (SAR) have also been established.
• Design, synthesis and biological activities of thiourea containing sorafenib analogs as antitumor agents
  作者：Jianwen Yao、Jing Chen、Zuopeng He、Wei Sun、Wenfang Xu

  DOI：10.1016/j.bmc.2012.03.018

  日期：2012.5

  sorafenib derivatives 9a–t was designed and synthesized. The structures of all the newly synthesized compounds were determined by 1H NMR, 13C NMR and HRMS. Their antiproliferative activities against HCT116 and MDA-MB-231 cell lines, and their inhibitory activities against the phosphorylation of VEGFR were evaluated and described. Some of the compounds showed significant activities against both cell lines

  设计并合成了一系列新型的含有索拉非尼衍生物9a – t的二芳基硫脲。所有新合成的化合物的结构均通过1 H NMR，13 C NMR和HRMS确定。评估并描述了它们对HCT116和MDA-MB-231细胞系的抗增殖活性，以及​​对VEGFR磷酸化的抑制活性。一些化合物对细胞系和VEGFR均显示出显着活性。化合物9g，9m，9o和9p对参考标准索拉非尼具有竞争性抗增殖活性，而化合物9d，9m和9p显示出对VEGFR的磷酸化的显着抑制活性。
• Design, synthesis and biological activities of sorafenib derivatives as antitumor agents
  作者：Jianwen Yao、Zuopeng He、Jing Chen、Wei Sun、Hao Fang、Wenfang Xu

  DOI：10.1016/j.bmcl.2012.09.031

  日期：2012.11

  A series of novel sorafenib derivatives, 9a-w, was designed and synthesized in high yields using various substituted anilines, and their antiproliferative activities against HCT116, PC-3 and MDA-MB-231 cell lines were also evaluated and described. All compounds exhibited potent antiproliferative activity against HCT116 and PC-3 cells with IC50 = 2.8-52.0 and 2.2-45.6 mu M; compounds 9p and 9q demonstrated competitive antiproliferative activities to sorafenib against all three cancer cell lines, the cytotoxicity of compound 9r is more potent than that of sorafenib. Compounds (9g, 9p, 9q and 9r) were chosen for further evaluation of the anti-angiogenesis activity, and showed the inhibition of sprout formation from aortic ring ex vivo. The structures of all the newly synthesized compounds were determined by H-1 NMR, C-13 NMR and HRMS. (C) 2012 Elsevier Ltd. All rights reserved.