4-羟基-6-三氟甲基喹啉-3-甲酸乙酯 | 26893-12-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 4-羟基-6-三氟甲基喹啉-3-甲酸乙酯
• 英文名称: ethyl 4-oxo-6-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylate
• 英文别名: ethyl 6-trifluoromethyl-4(1H)-quinolone-3-carboxylate；ethyl 6-(trifluoromethyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate；ethyl 4-oxo-6-(trifluoromethyl)-1H-quinoline-3-carboxylate
• CAS: 26893-12-9
• 化学式: C₁₃H₁₀F₃NO₃
• 分子量: 285.223
• InChiKey: SPGPSFWOMJQSDF-UHFFFAOYSA-N

物化性质

• 熔点：
  336(dec.)
• 沸点：
  343.5±37.0 °C(Predicted)
• 密度：
  1.404±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2933499090
• 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: Ethyl 4-hydroxy-6-(trifluoromethyl)quinoline-3-carboxylate
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: Ethyl 4-hydroxy-6-(trifluoromethyl)quinoline-3-carboxylate
CAS number: 26893-12-9

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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: C13H10F3NO3
Molecular weight: 285.2

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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 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：

  4-羟基-6-三氟甲基喹啉-3-甲酸乙酯 在 三氯氧磷 作用下， 生成 4-氯-6-三氟甲基-喹啉-3-羧酸乙酯
  参考文献：
  名称：

  喹啉作为强效和选择性PDE5抑制剂，可作为治疗勃起功能障碍的潜在药物。

  摘要：

  在不断发现新的化学型作为治疗男性勃起功能障碍（ED）的有效和选择性PDE5抑制剂的过程中，我们发现4-苄基氨基喹啉衍生物是非常有效和选择性的PDE5抑制剂。该系列中的某些化合物的PDE5 IC（50）低至50 pM。喹啉C6-位的吸电子基团大大提高了PDE5的效力，而C8-位的乙基不仅提高了PDE5的效力，而且提高了同工酶的选择性。在C3位的取代基可以结合各种不同的基团。描述了这一新系列有效的PDE5抑制剂的合成及其一级结构-活性关系。

  DOI：

  10.1016/j.bmcl.2003.12.090
• 作为产物：
  描述：

  乙氧基甲叉丙二酸二乙酯 以 乙醇 为溶剂， 反应 4.5h， 生成 4-羟基-6-三氟甲基喹啉-3-甲酸乙酯
  参考文献：
  名称：

  Hybrids of Imatinib with Quinoline: Synthesis, Antimyeloproliferative Activity Evaluation, and Molecular Docking

  摘要：

  伊马替尼（IMT）是第一类BCR-ABL商业酪氨酸激酶抑制剂（TKI）。然而，与IMT使用相关的耐药性和毒性突出了寻找新的TKI的重要性。在这种背景下，如喹啉等杂环系统，在TKI抑制剂博舒替尼（BST）的结构中作为药效团存在，已被广泛应用。因此，这项工作旨在获得含喹啉基团的伊马替尼新杂合物，并对其在K562细胞中进行评估。这些化合物以高纯度合成。在所制造的分子中，抑制剂4-甲基-N3-(4-(吡啶-3-基)嘧啶-2-基)-N1-(喹啉-4-基)苯-1,3-二胺（2g）显示出细胞活力适当降低，CC50值为0.9 µM（IMT，CC50 = 0.08 µM）。分子对接结果表明，最活跃的抑制剂2g与BCR-ABL1酶之间的相互作用通过竞争性抑制机制发生在博舒替尼结合位点。尽管比IMT更不具有潜力和选择性，但2g是一种适合用于寻找针对慢性髓样白血病（CML）的新药物的原型，特别是对于对IMT产生获得性耐药性的患者。

  DOI：

  10.3390/ph15030309

文献信息

• Conjugate Addition Routes to 2‐Alkyl‐2,3‐dihydroquinolin‐4(1 <i>H</i> )‐ones and 2‐Alkyl‐4‐hydroxy‐1,2‐dihydroquinoline‐3‐carboxylates
  作者：Alex Kingsbury、Steve Brough、Antonio Pedrina McCarthy、William Lewis、Simon Woodward

  DOI：10.1002/ejic.201901036

  日期：2020.3.27

  quinolin‐4(1H)‐ones to provide 2‐alkyl‐2,3‐dihydroquinolin‐4(1H)‐ones (14 examples, 54–99 % yield). Asymmetric versions require AlEt3 to Boc‐protected ethyl 6‐substituted 4(1H)‐quinolone‐3‐carboxylates (6‐R group = all halogens, n/i/t‐alkyls, CF3) and provide 61–91 % yield, 30–86 % ee; any halogen, Me, or CF3 provide the highest stereoselectivities (76–86 % ee). Additions of AlMe3 or Al(nC8H17)3 provide ≈ 45 and

  在CuBr · SMe2 / PPh3催化下（5/10 mol％）RMgCl（R = Me，Et，n Pr，CH = CH 2，n Bu，i Bu，n C 5 H 11，c C 6 H 11，Bn ，CH 2 Bn，n C 11 H 23）容易地（–78°C）对Cbz或Boc保护的喹啉-4（1 H）-酮进行1,4加成，从而提供2-烷基-2-3,2-二氢喹啉- 4（1 H）-1 （14例，产率54–99％）。非对称版本需要AlEt 3到Boc保护的乙基6取代的4（1 H）-喹诺酮-3-羧酸盐（6-R基团=所有卤素，n / i / t-烷基，CF 3），收率61-91％，ee 30-86％; 任何卤素，Me或CF 3均可提供最高的立体选择性（76–86％ee）。AlMe 3或Al（n C 8 H 17）3的添加在母体中的添加提供≈45和≈75％ee（6-R = H）。配体（S）‐（BINOL）P–N（CHPh
• Design, synthesis, in vitro and in silico studies of novel 4-oxoquinoline ribonucleoside derivatives as HIV-1 reverse transcriptase inhibitors
  作者：Luana da S.M. Forezi、Mariana M.J. Ribeiro、Andressa Marttorelli、Juliana L. Abrantes、Carlos R. Rodrigues、Helena Carla Castro、Thiago Moreno L. Souza、Fernanda da C.S. Boechat、Alessandra M.T. de Souza、Maria Cecília B.V. de Souza

  DOI：10.1016/j.ejmech.2020.112255

  日期：2020.5

  enzyme reverse transcriptase (RT) represents a validated therapeutic target. Because the oxoquinolinic scaffold has substantial biological activities, including antiretroviral, a new series of 4-oxoquinoline ribonucleoside derivatives obtained by molecular hybridization were studied here. All synthesized compounds were tested against human immunodeficiency virus type 1 reverse transcriptase (HIV-1

  1型人类免疫缺陷病毒（HIV-1）是一个公共卫生问题，全世界有3800万人受到影响。尽管有高效的抗逆转录病毒疗法，但抗病毒耐药菌株的出现是一个问题，每年导致近一百万人死亡。因此，开发新药是必要的。病毒酶逆转录酶（RT）代表经过验证的治疗靶标。由于氧喹喹啉类支架具有强大的生物学活性，包括抗逆转录病毒，因此，本文研究了通过分子杂交获得的一系列新的4-氧喹啉核糖核苷衍生物。测试了所有合成的化合物的人类免疫缺陷病毒1型逆转录酶（HIV-1 RT）以及9a和9d表现出最高的抗病毒活性，IC 50值分别为1.4和1.6μM。这些化合物的细胞毒性低于AZT，CC 50值分别为1486和1394μM。分子对接研究表明，活性最高的化合物与酶的变构位点结合，表明对抗病毒抗药性的敏感性较低。在计算机上进行的药代动力学和毒理学评估增强了该活性化合物作为抗HIV候选药物的潜力，可供进一步探索。总体而言，这项工作表明化合物9a和9d是用于未来抗HIV-1
• One-Pot Approach to Pyrido-4-phenanthridinones by Palladium-Catalyzed Annulation of 4-Quinolones with 2-Bromobenzyl Bromides
  作者：Athar Ata、Palathurai Mohan、Thangaraj Arasakumar、Selvaraj Shyamsivappan、Subashini Gopalan

  DOI：10.1055/s-0037-1610333

  日期：2019.1

  A straightforward approach toward the assembly of phenanthridinone heterocycles has been developed through the palladium-catalyzed N-benzylation/intramolecular coupling reactions of readily prepared 4-quinolones with commercially available 2-bromobenzyl bromide derivatives. The target products were prepared in moderate to good yields, with tolerance of various functional groups.

  已经通过钯催化的N-苄基化/分子内偶联反应的直接方法，成功地组装了苯并喹啉酮杂环。该方法利用易于制备的4-喹啉酮与市售2-溴苄溴衍生物进行反应，产物收率在中等到良好之间，并且对各种官能团具有一定的耐受性。
• THERAPEUTIC PYRAZOLOQUINOLINE UREA DERIVATIVES
  申请人：Kaplan Alan P.

  公开号：US20080306048A1

  公开（公告）日：2008-12-11

  The invention provides a novel chemical series of formula I, as well as methods of use thereof for binding to the benzodiazepine site of the GABA A receptor and modulating GABA A , and use of the compound of formula I for the treatment of GABA A receptor associated disorders. The general structure of formula I is shown below: The invention further provides a method of modulation of one or more GABA A subtypes in an animal comprising administering to the animal an effective amount of a compound of formula (I).

  该发明提供了一种新的化学系列，其化学式为I，以及使用该系列的方法，用于结合到GABAA受体的苯二氮卓位点并调节GABAA，并且使用化合物I的化学式进行治疗GABAA受体相关疾病。化学式I的一般结构如下所示：该发明还提供了一种调节动物体内一个或多个GABAA亚型的方法，包括向动物投与化学式(I)化合物的有效量。
• Quinolines as extremely potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunction
  作者：Yingzhi Bi、Patrick Stoy、Leonard Adam、Bin He、John Krupinski、Diane Normandin、Ron Pongrac、Laurie Seliger、Andrew Watson、John E Macor

  DOI：10.1016/j.bmcl.2003.12.090

  日期：2004.3

  novel chemotypes as potent and selective PDE5 inhibitors for the treatment of male erectile dysfunction (ED), we have found that 4-benzylaminoquinoline derivatives are very potent and selective PDE5 inhibitors. Some compounds in this series had PDE5 IC(50)'s as low as 50 pM. While an electron withdrawing group at the C6-position of the quinoline substantially improved PDE5 potency, an ethyl group at the

  在不断发现新的化学型作为治疗男性勃起功能障碍（ED）的有效和选择性PDE5抑制剂的过程中，我们发现4-苄基氨基喹啉衍生物是非常有效和选择性的PDE5抑制剂。该系列中的某些化合物的PDE5 IC（50）低至50 pM。喹啉C6-位的吸电子基团大大提高了PDE5的效力，而C8-位的乙基不仅提高了PDE5的效力，而且提高了同工酶的选择性。在C3位的取代基可以结合各种不同的基团。描述了这一新系列有效的PDE5抑制剂的合成及其一级结构-活性关系。