1-(4-溴-3-氟苯基)环丙烷-1-羧酸 | 749269-74-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(4-溴-3-氟苯基)环丙烷-1-羧酸
• 英文名称: 1-(4-bromo-3-fluorophenyl)cyclopropanecarboxylic acid
• 英文别名: 1-(4-bromo-3-fluoro-phenyl)-cyclopropanecarboxylic acid；4-bromo-3-fluorophenylcyclopropanecarboxylic acid；1-(4-Bromo-3-fluorophenyl)cyclopropane-1-carboxylic acid
• CAS: 749269-74-7
• 化学式: C₁₀H₈BrFO₂
• 分子量: 259.075
• InChiKey: WKVFGGQPVGDERD-UHFFFAOYSA-N

物化性质

• 沸点：
  354.4±42.0 °C(Predicted)
• 密度：
  1.744±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2916399090
• 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: 1-(4-Bromo-3-fluorophenyl)cyclopropane-1-carboxylic acid
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: 1-(4-Bromo-3-fluorophenyl)cyclopropane-1-carboxylic acid
CAS number: 749269-74-7

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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: C10H8BrFO2
Molecular weight: 259.1

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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, hydrogen fluoride, 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

反应信息

• 作为反应物：
  描述：

  1-(4-溴-3-氟苯基)环丙烷-1-羧酸 在 四(三苯基膦)钯 、 碘 、 镍 、 sodium carbonate 、 potassium iodide 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 1-[4-(4-Bromophenyl)-3-fluorophenyl]cyclopropane-1-carboxylic acid
  参考文献：
  名称：

  Synthesis and Biological Activity of Flurbiprofen Analogues as Selective Inhibitors of β-Amyloid_1-42 Secretion

  摘要：

  Flurbiprofen, a nonsteroidal antiinflammatory drug (NSAID), has been recently described to selectively inhibit beta-amyloid(1-42) (A beta 42) secretion, the most toxic component of the senile plaques present in the brain of Alzheimer patients. The use of this NSAID in Alzheimer's disease (AD) is hampered by a significant gastrointestinal toxicity associated with cyclooxygenase (COX) inhibition. New flurbiprofen analogues were synthesized, with the aim of increasing A beta 42 inhibitory potency while removing anti-COX activity. In vitro ADME developability parameters were taken into account in order to identify optimized compounds at an early stage of the project. Appropriate substitution patterns at the alpha position of flurbiprofen allowed for the complete removal of anti-COX activity, while modifications at the terminal phenyl ring resulted in increased inhibitory potency on A beta 42 secretion. In rats, some of the compounds appeared to be well absorbed after oral administration and to penetrate into the central nervous system. Studies in a transgenic mice model of AD showed that selected compounds significantly decreased plasma A beta 42 concentrations. These new flurbiprofen analogues represent potential drug candidates to be developed for the treatment of AD.

  DOI：

  10.1021/jm0502541
• 作为产物：
  描述：

  4-溴-3-氟甲苯 在 sodium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 四丁基溴化铵 、 过氧化苯甲酰 作用下， 以 甲醇 、 四氯化碳 、 乙醇 、 甲苯 为溶剂， 反应 15.0h， 生成 1-(4-溴-3-氟苯基)环丙烷-1-羧酸
  参考文献：
  名称：

  Synthesis and Biological Activity of Flurbiprofen Analogues as Selective Inhibitors of β-Amyloid_1-42 Secretion

  摘要：

  Flurbiprofen, a nonsteroidal antiinflammatory drug (NSAID), has been recently described to selectively inhibit beta-amyloid(1-42) (A beta 42) secretion, the most toxic component of the senile plaques present in the brain of Alzheimer patients. The use of this NSAID in Alzheimer's disease (AD) is hampered by a significant gastrointestinal toxicity associated with cyclooxygenase (COX) inhibition. New flurbiprofen analogues were synthesized, with the aim of increasing A beta 42 inhibitory potency while removing anti-COX activity. In vitro ADME developability parameters were taken into account in order to identify optimized compounds at an early stage of the project. Appropriate substitution patterns at the alpha position of flurbiprofen allowed for the complete removal of anti-COX activity, while modifications at the terminal phenyl ring resulted in increased inhibitory potency on A beta 42 secretion. In rats, some of the compounds appeared to be well absorbed after oral administration and to penetrate into the central nervous system. Studies in a transgenic mice model of AD showed that selected compounds significantly decreased plasma A beta 42 concentrations. These new flurbiprofen analogues represent potential drug candidates to be developed for the treatment of AD.

  DOI：

  10.1021/jm0502541

文献信息

• [EN] 1,2-DIHYDRO-3H-PYRROLO[1,2-C]IMIDAZOL-3-ONE DERIVATIVES AND THEIR USE AS ANTIBACTERIAL AGENTS<br/>[FR] DÉRIVÉS 1,2-DIHYDRO-3H-PYRROLO[1,2-C]IMIDAZOL-3-ONE ET LEUR UTILISATION EN TANT QU'AGENTS ANTIBACTÉRIENS
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2015132228A1

  公开（公告）日：2015-09-11

  The invention relates to antibacterial compounds of formula (I), wherein R1 is one of the groups represented below (AA), wherein A is a bond, CH=CH or C≡C; U is N or CH; V is N or CH; W represents N or CH; and R1A, R2A, R3A, R1B and R1C are as defined in the claims; and salts thereof.

  这项发明涉及公式（I）的抗菌化合物，其中R1是下面表示的一组（AA），其中A是键，CH=CH或C≡C；U是N或CH；V是N或CH；W代表N或CH；而R1A、R2A、R3A、R1B和R1C如权利要求中所定义的；以及其盐。
• Systematic Investigation of Halogen Bonding in Protein–Ligand Interactions
  作者：Leo A. Hardegger、Bernd Kuhn、Beat Spinnler、Lilli Anselm、Robert Ecabert、Martine Stihle、Bernard Gsell、Ralf Thoma、Joachim Diez、Jörg Benz、Jean‐Marc Plancher、Guido Hartmann、David W. Banner、Wolfgang Haap、François Diederich

  DOI：10.1002/anie.201006781

  日期：2011.1.3

  Halogen bonding triggers activity: Increasing binding affinity was observed for a series of covalent human Cathepsin L inhibitors by exchanging an aryl ring H atom with Cl, Br, and I, which undergo halogen bonding with the CO group of Gly61 in the S3 pocket of the enzyme. Fluorine, in contrast, strongly avoids halogen bonding (see scheme). The strong distance and angle dependence of halogen bonding

  卤素键触发活性：通过将芳环H原子与Cl，Br和I交换，可以观察到一系列共价的人组织蛋白酶L抑制剂的结合亲和力增加，Cl，Br和I与S3口袋中的Gly61的CO基团进行卤素键合酶。相反，氟强烈避免卤素键（参见方案）。卤素键的强距离和角度依赖性已被证实适用于生物系统。
• [EN] 1-PHENYLALKANECARBOXYLIC ACID DERIVATIVES FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] DERIVES D'ACIDE 1-PHENYLALCANE-CARBOXYLIQUE POUR LE TRAITEMENT DE MALADIES NEURODEGENERATIVES
  申请人：CHIESI FARMA SPA

  公开号：WO2004074232A1

  公开（公告）日：2004-09-02

  1-Phenylalkanecarboxylic acid derivatives, the processes for the preparation thereof and the use thereof in the treatment and/or prevention of neurodegenerative diseases such as Alzheimer's disease.

  1-苯基烷基羧酸衍生物，其制备方法以及用于治疗和/或预防如阿尔茨海默病等神经退行性疾病的使用方法。
• [EN] CATHEPSIN CYSTEINE PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DES PROTEASES A CYSTEINE DU TYPE CATHEPSINE
  申请人：MERCK FROSST CANADA INC

  公开号：WO2005056529A1

  公开（公告）日：2005-06-23

  This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

  这项发明涉及一类新型化合物，它们是半胱氨酸蛋白酶抑制剂，包括但不限于对卡特普辛K、L、S和B的抑制剂。这些化合物对于治疗需要抑制骨吸收的疾病，如骨质疏松症，非常有用。
• Chiral Bidentate Boryl Ligand Enabled Iridium-Catalyzed Enantioselective C(sp³)–H Borylation of Cyclopropanes
  作者：Yongjia Shi、Qian Gao、Senmiao Xu

  DOI：10.1021/jacs.9b04549

  日期：2019.7.10

  We herein report an Ir-catalyzed enantioselective C(sp3)-H borylation of cyclopropanecarboxamides using a chiral bidentate boryl ligand for the first time. A variety of substrates with α-quaternary carbon centers could be compatible in this reaction to provide β-borylated products with good to excellent enantioselectivities. We have also demonstrated that the borylated products can be used as versatile

  我们在此报告了首次使用手性双齿硼酸配体对环丙烷甲酰胺进行 Ir 催化的对映选择性 C(sp3)-H 硼酸化。具有 α-季碳中心的多种底物可以在该反应中相容，以提供具有良好至优异对映选择性的 β-硼酸化产物。我们还证明，硼酸化产物可用作多功能前体，参与 CB 键的立体有择转化，包括合成生物活性化合物 Levomilnacipran。