阿克他利 | 18699-02-0

• 物质功能分类: 生物化工 - 生物反应调节剂
• 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: 阿克他利
• 中文别名: 埃他利特；4-乙酰胺基苯乙酸
• 英文名称: 4-acetamidophenylacetic acid
• 英文别名: actarit；2-(4-acetamidophenyl)acetic acid
• CAS: 18699-02-0
• 化学式: C₁₀H₁₁NO₃
• mdl: MFCD00196165
• 分子量: 193.202
• InChiKey: MROJXXOCABQVEF-UHFFFAOYSA-N

物化性质

• 熔点：
  173-175°C
• 沸点：
  449.1±28.0 °C(Predicted)
• 密度：
  1.288±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO、乙醇、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 安全说明：
  S24/25,S26,S27,S28,S36/37/39,S45
• 海关编码：
  29163990
• 危险品标志：
  C
• RTECS号：
  CY1542000
• 危险类别：
  8
• 危险类别码：
  R34
• 包装等级：
  II
• 危险品运输编号：
  2987
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  -20°C

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Actarit
Synonyms: [4-(Acetylamino)phenyl]acetic acid

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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: Actarit
CAS number: 18699-02-0

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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: C10H11NO3
Molecular weight: 193.2

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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.

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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

作用机制

阿克他利属于新型非甾体类抗风湿药物，具有明显的抗炎作用。它对急性炎症及佐剂性关节炎大鼠模型有较好的抑制效果。研究表明，阿克他利能够显著抑制Ⅱ型胶原诱导的小鼠足肿胀，并恢复其过高的刀豆素增殖反应和白介素（IL）-2 的产生至接近正常水平。同时，它还对Ⅱ型胶原性关节炎小鼠过度的IL -1 产生有明显的抑制作用。

阿克他利可以明显减轻由Ⅱ型胶原诱发的迟发型变态反应，但对Ⅱ型胶原性关节炎小鼠体内抗体的产生无显著影响。病理学检查显示，该药物能减轻Ⅱ型胶原性关节炎小鼠的骨膜增生和软骨破坏。

此外，阿克他利还显示出显著的双向免疫调节作用。它能够抑制由大剂量环磷酰胺造成的迟发型超敏反应（DTH）增强，并恢复由环磷酰胺引起的DTH 低下。这种调节作用是通过调节T细胞亚群，改善Th/Ts的比例来实现的。

阿克他利还能降低血清一氧化氮（NO）水平等，控制活动性类风湿性关节炎的发展，尤其是对早期类风湿性关节炎的疗效更为显著。它还具有减少滑膜炎症、软骨浸蚀及骨破坏的作用，并可能对多发性硬化症等神经免疫性疾病产生潜在疗效。

药理作用

阿克他利不同于目前临床上使用的非甾体抗炎药，无明显的抗炎作用，但具有显著的免疫调节作用。它能够抑制由大剂量环磷酰胺造成的DTH 增强，并恢复由环磷酰胺引起的小鼠DTH 低下。这种双向免疫调节作用是通过调节T 细胞亚群，改善Th/Ts 的比例来发挥作用。

阿克他利的药理作用还能降低血清一氧化氮（NO）水平等，控制活动性类风湿性关节炎的发展，尤其是对早期类风湿性关节炎有较好的疗效。它能够减少滑膜炎症、软骨浸蚀及骨破坏，并可能对多发性硬化症等神经免疫性疾病产生潜在疗效。

临床应用

临床上阿克他利主要用于治疗慢性类风湿性关节炎。一项研究中，选择了75例疾病活动期RA患者进行随机、单盲对照试验。治疗组（45例）使用阿克他利100mg，3次/d；对照组（30例）使用甲氨蝶呤（MTX） 10mg，1次/w，疗程为12周。

结果显示，在第12周时两组疗效无显著统计学差异（P > 0.05），但阿克他利的耐受性优于MTX（P < 0.05）。阿克他利对RA患者具有良好的治疗作用且副作用较小。

生物活性

Actarit (4-acetylaminophenylacetic acid)是一种具有口服活性的免疫调节剂，用于治疗类风湿性关节炎。它属于针对类风湿性关节炎的一代免疫调节剂，并归类为免疫调节药。

用途：针对类风湿性关节炎的一代免疫调节剂；免疫调节药

反应信息

• 作为反应物：
  描述：

  阿克他利 在 iron(III) trifluoromethanesulfonate 、 sodium nitrite 作用下， 以 二甲基亚砜 为溶剂， 反应 10.0h， 以51%的产率得到4-乙酰氨苯甲腈
  参考文献：
  名称：

  铁促进芳基乙酸脱羧反应以亚硝酸钠为氮源合成芳香腈

  摘要：

  以 NaNO2 为氮源，Fe(OTf)3 为促进剂，在 50 °C 条件下，开发了一种由芳基乙酸合成芳香腈的新方法。一系列芳基乙酸经历了这种转变，以 51-90% 的产率得到目标产物。由于条件温和，该反应与广泛的官能团相容，包括酯、羧基、羟基、乙酰氨基、卤素、硝基、氰基、甲氧基，甚至高反应性甲酰基。

  DOI：

  10.1055/s-0040-1707300
• 作为产物：
  描述：

  4-(2-硝基乙烯基)苯胺 在 钾硼氢 、 溶剂黄146 、 sodium nitrite 作用下， 以 乙醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 阿克他利
  参考文献：
  名称：

  Zhou, Li-Yi; Yang, Jun; Yan, Xi-Qing, Asian Journal of Chemistry, 2012, vol. 24, # 4, p. 1538 - 1540

  摘要：

  DOI：

文献信息

• [EN] ROR-GAMMA INHIBITORS<br/>[FR] INHIBITEURS DE ROR-GAMMA
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2019063748A1

  公开（公告）日：2019-04-04

  The present invention relates to compounds of formula I and pharmaceutical compositions comprising compounds of formula I. Compounds of Formula I are useful in treatment of inflammatory, metabolic or autoimmune diseases which are mediated by RORy.

  本发明涉及公式I的化合物和包含公式I化合物的药物组合物。公式I的化合物在治疗由RORγ介导的炎症性、代谢性或自身免疫性疾病方面是有用的。
• [EN] NOVEL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2015180612A1

  公开（公告）日：2015-12-03

  Disclosed are novel retinoid-related orphan receptor gamma (RORγ) modulators and their use in the treatment of diseases mediated by RORγ.

  揭示了新型视黄醇相关孤儿受体γ（RORγ）调节剂及其在通过RORγ介导的疾病治疗中的应用。
• Boron trifluoride–methanol complex. Mild and powerful reagent for deprotection of acetylated amines. Scope and selectivity
  作者：Sergey Miltsov、Vladimir Karavan、Alexandr Misharev、Julian Alonso-Chamarro、Mar Puyol

  DOI：10.1016/j.tetlet.2015.12.087

  日期：2016.2

  A boron trifluoride–methanol complex demonstrated remarkable deprotection selectivity against commonly used amino-protecting groups in the deacetylation of acetanilides and high sensitivity to the steric hindrance of substrates. The scope and limitations of the reaction were explored.

  三氟化硼-甲醇络合物在对乙酰苯胺的脱乙酰作用中对常用的氨基保护基团表现出显着的脱保护选择性，并对底物的空间位阻高度敏感。探索了反应的范围和局限性。
• TROPAN COMPOUND
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1785421A1

  公开（公告）日：2007-05-16

  The conventional anticholinergic drugs for administration through inhalation have been considered to have the possibility of aggravating dysuria associated with prostatic hyperplasia mediated by blood, and it has been demanded that the conventional anticholinergic drugs for administration through inhalation will have to show reduced side effects or adverse ractions. The present invention relates to a compound represented by the general formula (I): (wherein A represents; and R1, R2, R3 and R1 each a hydrogen atom or a substituent; R5 is a substituent; X- is an anion;the symbol: denotes an exo-form or endo-form, or their mixture), its salt or solvation product thereof. They are useful as a prophylactic and/or therapeutic agent with reduced side effects or adverse reactions for the diseases mediated by the muscarinic receptor.

  传统的抗胆碱药物通过吸入给药被认为可能加重与前列腺增生相关的排尿困难，并要求传统的抗胆碱药物通过吸入给药必须显示减少副作用或不良反应。 本发明涉及一种由通式（I）表示的化合物： （其中A代表; 和R1、R2、R3和R1分别是氢原子或取代基; R5是取代基; X-是阴离子;符号: 表示外向型或内向型，或它们的混合物），其盐或溶剂化产物。它们可用作通过胆碱受体介导的疾病的预防和/或治疗剂，具有减少副作用或不良反应。
• Green Esterification of Carboxylic Acids Promoted by <i>tert</i> ‐Butyl Nitrite
  作者：Yonggao Zheng、Yanwei Zhao、Suyan Tao、Xingxing Li、Xionglve Cheng、Gangzhong Jiang、Xiaobing Wan

  DOI：10.1002/ejoc.202100326

  日期：2021.5.14

  TBN‐catalyzed green esterification of carboxylic acids has been developed, which features a broad range of substrates and excellent functional groups tolerance. The mechanistic study confirmed that the nitrous acid formed in situ in the system is the actual catalyst for this transformation.

  已经开发了TBN催化的羧酸绿色酯化反应，它具有多种底物和出色的官能团耐受性。机理研究证实，在系统中原位形成的亚硝酸是该转化的实际催化剂。