氟喹酮 | 56287-74-2

• 物质功能分类: 原料药 - 麻醉剂 - 骨骼肌松弛药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 氟喹酮
• 中文别名: 6-氨基-2-(氟甲基)-3-(2-甲基苯基)-4-(3H)-1,3-二氮杂萘酮
• 英文名称: Afloqualone
• 英文别名: 6-amino-2-fluoromethyl-3-(o-tolyl)-4(3H)-quinazolinone；6-amino-2-(fluoromethyl)-3-(2-methylphenyl)quinazolin-4-one
• CAS: 56287-74-2
• 化学式: C₁₆H₁₄FN₃O
• mdl: MFCD00867693
• 分子量: 283.305
• InChiKey: VDOSWXIDETXFET-UHFFFAOYSA-N

物化性质

• 熔点：
  195-196°C
• 沸点：
  492.5±55.0 °C(Predicted)
• 密度：
  1.2529 (estimate)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  58.7
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

Afloqualone 已知的代谢物包括 Afloqualone N-葡萄糖苷酸。

Afloqualone has known human metabolites that include Afloqualone N-glucuronide.

来源:NORMAN Suspect List Exchange

安全信息

• 储存条件：
  库房应保持通风、低温和干燥，并与其他食品原料分开存放。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Afloqualone
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: Afloqualone
CAS number: 56287-74-2

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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, refrigerated.
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: C16H14FN3O
Molecular weight: 283.3

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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

制备方法与用途

简介

氟喹酮于1983年在日本首次上市，由日本田边株式会社开发。经过二十多年的临床应用，证明它对面部、颈部肌肉痉挛具有良好的松弛效果。作为肌肉松弛药，氟喹酮主要通过作用于脊髓上位中枢较广泛的部位来缓解肌肉紧张性亢进状态。其中枢肌肉松弛活性大约是甲苯丙醇的22-29倍，是氯美扎酮的8-10倍。

生物活性

Afloqualone（HQ-495）是一种GABA能试剂，在GABAα受体的β亚型上表现出激动剂活性。Afloqualone具有抗眩晕和镇静作用，这被认为是因为它增加了LVN神经元部位GABA受体的敏感性。

靶点

Target	Value
GABAA β receptor

类别

有毒物品

毒性分级

高毒

急性毒性

• 口服-大鼠LD50：249毫克/公斤
• 口服-小鼠LD50：397毫克/公斤

可燃性危险特性

可燃；燃烧时释放有毒氮氧化物和氟化物烟雾

储运特性

库房应通风、低温干燥；与食品原料分开存放

灭火剂

干粉、泡沫、砂土、二氧化碳，雾状水

反应信息

• 作为反应物：
  描述：

  氟喹酮 在 碳酸氢钠 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 1.0h， 生成 N-glycolyl AFQ
  参考文献：
  名称：

  黄酮酮及其相关化合物的代谢产物的合成。

  摘要：

  七种主要代谢物（3-9号），如afloqualone（1号，6-氨基-2-氟甲基-3-(邻甲苯基)-4(3H)-喹唑啉酮）及相关4(3H)-喹唑啉酮衍生物，已被合成。带有硫原子的代谢物4和5是通过6-乙酰氨基-2-氯甲基-3-(邻甲苯基)-4(3H)-喹唑啉酮（11号）与NaSCH3反应，随后用H2O2氧化制备的。11号化合物与N-乙酰-L-半胱氨酸反应得到硫醇尿酸结合型代谢物6号。在1-羟基苯并三唑存在下，通过2-氟乙酰氨基-5-硝基苯甲酸（19号）与2-氨基苄醇（20号）与二环己基碳二亚胺（DCC）缩合，获得2-氟甲基-3-(邻羟甲基苯基)-6-硝基-4(3H)-喹唑啉酮（21号），进而转化为代谢物7号和8号。2-溴甲基-4(3H)-喹唑啉酮（24号）在二甲基亚砜（DMSO）中与AgBF4-H2O反应得到2-羟甲基代谢物9号。主要代谢物（2-9号）均未显示出显著的神经系统抑制活性。

  DOI：

  10.1248/cpb.31.1158
• 作为产物：
  描述：

  5-硝基靛红酸酐 在 potassium fluoride 、 四丁基溴化铵 、 氢气 、 溶剂黄146 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 乙腈 为溶剂， 20.0~70.0 ℃ 、2.0 MPa 条件下， 反应 17.33h， 生成 氟喹酮
  参考文献：
  名称：

  一种氟喹酮的制备方法

  摘要：

  本发明公开了一种氟喹酮的制备方法，该方法以靛红酸酐为起始原料，首先经硝化、还原、乙酰化合成了关键中间体N-（2-氨基-5-乙酰氨基苯甲酰基）邻甲苯胺，再经氨解、环合、氟交换、脱保护得到目标产物氟喹酮；本发明氟喹酮的制备方法，原料廉价易得，降低了生产成本，革除了现有文献方法中高毒高害试剂氟代乙酰氯的使用，具有安全、环保的优点，同时在氟交换反应中使用四丁基溴化铵作为反应的相转移催化剂，大大提高了该步反应的转化率，由起始原料靛红酸酐制备目标产物氟喹酮的总收率可达60.0%以上。

  公开号：

  CN103613549B

文献信息

• SUBSTITUTED DIHYDROPYRROLOPYRAZOLE DERIVATIVE
  申请人：UBE INDUSTRIES, LTD.

  公开号：US20180186818A1

  公开（公告）日：2018-07-05

  The present invention provides a compound represented by the general formula (Ia) or a pharmacologically acceptable salt thereof. In the general formula (Ia), two R moieties each independently represent a C 1-3 alkyl group or the like; and R 1 , R 2 and R 3 each independently represent an optionally substituted linear or branched C 1-4 alkyl group.

  本发明提供了一种由通用公式（Ia）表示的化合物或其药理可接受的盐。在通用公式（Ia）中，两个R基团各自独立地代表一个C1-3烷基团或类似物；而R1、R2和R3各自独立地代表一个可选地取代的线性或支链的C1-4烷基团。
• [EN] DIFLUOROMETHYLATION OF UNSATURATED COMPOUNDS<br/>[FR] DIFLUOROMÉTHYLATION DE COMPOSÉS INSATURÉS
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2013082028A1

  公开（公告）日：2013-06-06

  A reagent for carrying out a difluoromethylation reaction of unsaturated compounds and ring-nitrogen-containing aromatic compounds, a zinc difluoro-methanesulfinate, as well as a method for making the reagent and a method for its use are disclosed.

  一种用于执行不饱和化合物和含环氮芳香化合物的二氟甲基化反应的试剂，以及一种锌二氟甲磺酸酯，以及制造该试剂的方法及其用途。
• Nitric Oxide Releasing Prodrugs of Therapeutic Agents
  申请人：SATYAM Apparao

  公开号：US20110263526A1

  公开（公告）日：2011-10-27

  The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents which are represented herein as compounds of formula (I) wherein the drugs or therapeutic agents contain one or more functional groups independently selected from a carboxylic acid, an amino, a hydroxyl and a sulfhydryl group. The invention also relates to processes for the preparation of the nitric oxide releasing prodrugs (the compounds of formula (I)), to pharmaceutical compositions containing them and to methods of using the prodrugs.

  本发明涉及已知药物或治疗剂的一氧化氮释放前药，其在此处表示为式(I)的化合物，其中药物或治疗剂包含一个或多个功能基团，独立地选自羧酸、氨基、羟基和巯基。该发明还涉及制备一氧化氮释放前药（式(I)的化合物）的方法，含有它们的药物组合物以及使用这些前药的方法。
• [EN] POLYMERIC HYPERBRANCHED CARRIER-LINKED PRODRUGS<br/>[FR] PROMÉDICAMENTS LIÉS À DES EXCIPIENTS POLYMÉRIQUES HYPERBRANCHÉS
  申请人：ASCENDIS PHARMA AS

  公开号：WO2013024048A1

  公开（公告）日：2013-02-21

  The present invention relates to water-soluble carrier-linked prodrugs of formula (I),wherein POL is a polymeric moiety,each Hyp is independently a hyperbranched moiety,each moiety SP is independently a spacer moiety, each L is independently a reversible prodrug linker moiety, m is 0 or 1, each n is independently an integer from 2 to 200 and each x is independently 0 or 1. It further relates to pharmaceutical compositions comprising said water- soluble carrier-linked prodrugs and methods of treatment.

  本发明涉及水溶性载体连接的前药，其化学式为（I），其中POL是聚合物基团，每个Hyp是独立的超支化基团，每个基团SP是独立的间隔基团，每个L是独立的可逆前药连接基团，m为0或1，每个n是独立的整数，范围从2到200，每个x是独立的0或1。此外，还涉及包含所述水溶性载体连接的前药的药物组合物和治疗方法。
• 2-Fluoromethyl-3-o-tolyl-6-amino-4(3H)-quinazolinone
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US03966731A1

  公开（公告）日：1976-06-29

  N-(2-amino-5-nitrobenzoyl)-o-toluidine is condensed with fluoroacetic acid or a functional derivative thereof. N-(2-fluoroacetamido-5-nitrobenzoyl)-o-toluidine obtained by said condensation reaction is dehydrated to produce 2-fluoromethyl-3-(o-tolyl)-6-nitro-4(3H)-quniazolinone, which is then subjected to reduction reaction. 2-fluoromethyl-3-(o-tolyl)-6-amino-4(3H)-quinazolinone thus obtained and a pharmaceutically acceptable acid addition salt thereof are useful as central muscle relaxants, minor tranquilizers, anti-convulsants, analgesics and/or anti-inflammatory agents.

  N-(2-氨基-5-硝基苯甲酰基)-邻甲苯胺与氟乙酸或其功能衍生物缩合。通过该缩合反应得到的N-(2-氟乙酰氨基-5-硝基苯甲酰基)-邻甲苯胺脱水生成2-氟甲基-3-(邻甲苯基)-6-硝基-4(3H)-喹唑啉酮，随后进行还原反应。由此得到的2-氟甲基-3-(邻甲苯基)-6-氨基-4(3H)-喹唑啉酮及其药用可接受的酸加成盐可作为中枢肌肉松弛剂、轻度镇静剂、抗惊厥药、镇痛药和/或抗炎剂使用。