6-氯-8-氟咪唑并[1,2-a]吡啶 | 1033202-10-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 中文名称: 6-氯-8-氟咪唑并[1,2-a]吡啶
• 英文名称: 6-chloro-8-fluoroimidazo[1,2-a]pyridine
• CAS: 1033202-10-6
• 化学式: C₇H₄ClFN₂
• mdl: MFCD10699670
• 分子量: 170.574
• InChiKey: ICYMCPKHCXZHDA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  11
• 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：
  17.3
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,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-Chloro-8-fluoroimidazo[1,2-a]pyridine
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-Chloro-8-fluoroimidazo[1,2-a]pyridine
CAS number: 1033202-10-6

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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: C7H4ClFN2
Molecular weight: 170.6

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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, hydrogen fluoride.

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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-8-氟咪唑并[1,2-a]吡啶 在 N-溴代丁二酰亚胺(NBS) 、 乙基溴化镁 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 6.0h， 生成 (6-chloro-8-fluoroimidazo[1,2-a]pyridin-3-yl)(quinolin-6-yl)methanol
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Imidazo[1,2-a]pyridine Derivatives as Potent c-Met Inhibitors

  摘要：

  A series of imidazo[1,2-a]pyridine derivatives against c-Met was designed by means of bioisosteric replacement. In this study, a selective, potent c-Met inhibitor, 22e was identified, with IC50 values of 3.9 nM against c-Met kinase and 45.0 nM against c-Met-addicted EBC-1 cell proliferation, respectively. Compound 22e inhibited c-Met phosphorylation and downstream signaling across different oncogenic forms in c-Met overactivated cancer cells and model cells. Compound 22e significantly inhibited tumor growth (TGI = 75%) with good oral bioavailability (F = 29%) and no significant hERG inhibition. On the basis of systematic metabolic study, the pathway of all possible metabolites of 22e in liver microsomes of different species has been proposed, and a major NADPH-dependent metabolite 33 was generated by liver microsomes. To block the metabolic site, 42 was designed and synthesized for further evaluation. Taken together, the imidazo[1,2-a]pyridine scaffold showed promising pharmacological inhibition of c-Met and warrants further investigation.

  DOI：

  10.1021/ml5004876
• 作为产物：
  描述：

  氯乙醛 、 2-氨基-3-氟-5-氯吡啶 以 乙醇 为溶剂， 反应 8.0h， 以78%的产率得到6-氯-8-氟咪唑并[1,2-a]吡啶
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Imidazo[1,2-a]pyridine Derivatives as Potent c-Met Inhibitors

  摘要：

  A series of imidazo[1,2-a]pyridine derivatives against c-Met was designed by means of bioisosteric replacement. In this study, a selective, potent c-Met inhibitor, 22e was identified, with IC50 values of 3.9 nM against c-Met kinase and 45.0 nM against c-Met-addicted EBC-1 cell proliferation, respectively. Compound 22e inhibited c-Met phosphorylation and downstream signaling across different oncogenic forms in c-Met overactivated cancer cells and model cells. Compound 22e significantly inhibited tumor growth (TGI = 75%) with good oral bioavailability (F = 29%) and no significant hERG inhibition. On the basis of systematic metabolic study, the pathway of all possible metabolites of 22e in liver microsomes of different species has been proposed, and a major NADPH-dependent metabolite 33 was generated by liver microsomes. To block the metabolic site, 42 was designed and synthesized for further evaluation. Taken together, the imidazo[1,2-a]pyridine scaffold showed promising pharmacological inhibition of c-Met and warrants further investigation.

  DOI：

  10.1021/ml5004876

文献信息

• [EN] IMIDAZOPYRIDINE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS À BASE D'IMIDAZOPYRIDINE ET LEURS UTILISATIONS
  申请人：PIRAMAL ENTPR LTD

  公开号：WO2014080241A1

  公开（公告）日：2014-05-30

  The invention provides compounds of formula (1), stereoisomers and tautomers thereof, or pharmaceutically acceptable salts, solvates and polymorphs thereof, and processes for their preparation. The invention further relates to pharmaceutical compositions containing said compounds and their use in the treatment of diseases or disorders mediated by one or more proinflammatory cytokines selected from TNF-a, IL-Ιβ, IL-6, IL-8, IL-12, IL-17 or IL-23.

  该发明提供了式（1）的化合物，其立体异构体和互变异构体，或其药学上可接受的盐、溶剂合物和多型体，以及它们的制备方法。该发明还涉及含有上述化合物的药物组合物，以及它们在治疗由TNF-a、IL-Ιβ、IL-6、IL-8、IL-12、IL-17或IL-23中的一个或多个促炎细胞因子介导的疾病或疾病的用途。
• Design, Synthesis, and Biological Evaluation of Novel Imidazo[1,2-<i>a</i>]pyridine Derivatives as Potent c-Met Inhibitors
  作者：Chunpu Li、Jing Ai、Dengyou Zhang、Xia Peng、Xi Chen、Zhiwei Gao、Yi Su、Wei Zhu、Yinchun Ji、Xiaoyan Chen、Meiyu Geng、Hong Liu

  DOI：10.1021/ml5004876

  日期：2015.5.14

  A series of imidazo[1,2-a]pyridine derivatives against c-Met was designed by means of bioisosteric replacement. In this study, a selective, potent c-Met inhibitor, 22e was identified, with IC50 values of 3.9 nM against c-Met kinase and 45.0 nM against c-Met-addicted EBC-1 cell proliferation, respectively. Compound 22e inhibited c-Met phosphorylation and downstream signaling across different oncogenic forms in c-Met overactivated cancer cells and model cells. Compound 22e significantly inhibited tumor growth (TGI = 75%) with good oral bioavailability (F = 29%) and no significant hERG inhibition. On the basis of systematic metabolic study, the pathway of all possible metabolites of 22e in liver microsomes of different species has been proposed, and a major NADPH-dependent metabolite 33 was generated by liver microsomes. To block the metabolic site, 42 was designed and synthesized for further evaluation. Taken together, the imidazo[1,2-a]pyridine scaffold showed promising pharmacological inhibition of c-Met and warrants further investigation.