右旋酮洛芬 | 22161-81-5

• 物质功能分类: 化学试剂 - 有机试剂 - 脂肪酮(含烯醇)
• 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: 右旋酮洛芬
• 中文别名: (S)-(+)-酮洛芬；(S)-酮洛芬；(S)-(+)-2-(3-苯甲酰基苯基)丙酸
• 英文名称: S-ketoprofen
• 英文别名: dexketoprofen；(+)-(S)-2-(3-benzoylphenyl)propionic acid；(+)-Ketoprofen；(S)-2-(3-benzoylphenyl)propanoic acid；(2S)-2-(3-benzoylphenyl)propanoic acid
• CAS: 22161-81-5
• 化学式: C₁₆H₁₄O₃
• 分子量: 254.285
• InChiKey: DKYWVDODHFEZIM-NSHDSACASA-N

物化性质

• 熔点：
  75-78 °C(lit.)
• 沸点：
  431.3±28.0 °C(Predicted)
• 密度：
  1.198±0.06 g/cm3(Predicted)
• 溶解度：
  不溶于水； DMSO 中≥10.6 mg/mL；乙醇中≥20.55 mg/mL
• 稳定性/保质期：
  常温常压下稳定，避免与氧化物接触。

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

.dexketoprofen是一种高度脂溶性的药物，通过肝脏的葡萄糖醛酸化进行代谢。在一项研究中，对年轻健康的成年人进行了一次口服25毫克的.dexketoprofen，其Tmax大约为30分钟，Cmax为3.7±0.72毫克/升。.dexketoprofen的代谢是通过肝脏细胞色素P450酶(CYP2C8和CYP2C9)进行的。.dexketoprofen有许多代谢物，其中羟基衍生物占据了最大的比例。在人体内，羟基化只起到了较小的作用。.dexketoprofen主要是与酰基葡萄糖醛酸结合

Dexketoprofen is highly lipophilic, and is metabolized in the liver by glucuronidation. In one study, after oral administration of 25 mg of dexketoprofen to young healthy adults, Tmax was approximately 30 min for a Cmax of 3.7 ± 0.72 mg/l. Dexketoprofen trometamol is metabolized by the hepatic cytochrome P450 enzymes (CYP2C8 and CYP2C9). Dexketoprofen trometamol has a number of metabolites, with hydroxyl derivatives making up the greatest volume. In humans, hydroxylation plays a minor role. Dexketoprofen is primarily conjugated to an acyl-glucuronide

来源:DrugBank

毒理性

• 蛋白质结合

高度蛋白质结合。

Highly protein bound.

来源:DrugBank

吸收、分配和排泄

• 吸收

口服给药后，戴克托普洛芬的作用开始时间在30分钟内。戴克托普洛芬的血浆半衰期约为4-6小时。Cmax约为30分钟。

After oral ingestion, the Dexketoprofen onset of action is within 30 minutes. The plasma half-life of Dexketoprofen is about 4-6 hours. The Cmax is about 30 minutes

来源:DrugBank

吸收、分配和排泄

• 消除途径

摄入剂量的约70至80%在摄入后前12小时内通过尿液排出，主要是药物的酰基结合形式。

Approximately 70 to 80% of the ingested dose is recovered in the urine during the first 12 hours post-ingestion, mainly as the acyl-conjugated form of the drug.

来源:DrugBank

吸收、分配和排泄

• 分布容积

0.25 升/千克

<0.25 L/kg

来源:DrugBank

吸收、分配和排泄

• 清除

主要通过葡萄糖醛酸苷结合反应进行清除，随后通过肾脏排泄，主要以原形排出。

Mainly cleared via glucuronide conjugation and followed by renal excretion, mainly unchanged.

来源:DrugBank

安全信息

• 危险品标志：
  Xn,T
• 安全说明：
  S26,S60,S61
• 危险类别码：
  R22,R36/37/38,R25,R50/53
• WGK Germany：
  3
• 危险品运输编号：
  UN 2811 6
• RTECS号：
  CY1572790
• 海关编码：
  2942000000
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 危险性防范说明：
  P261,P273,P301+P310,P305+P351+P338
• 危险性描述：
  H301,H315,H319,H335,H400
• 储存条件：
  应存放在密闭、避光、通风干燥的地方。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: (S)-(+)-Ketoprofen
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H301: Toxic if swallowed
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
Very toxic to aquatic life
H400:
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
P273: Avoid release to the environment
P301+P310: IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing

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Section 3. Composition/information on ingredients.
Ingredient name: (S)-(+)-Ketoprofen
CAS number: 22161-81-5

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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
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C16H14O3
Molecular weight: 254.3

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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.

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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
UN Number: UN2811 Class: 6.1 Packing group: III
Proper shipping name: TOXIC SOLIDS, ORGANIC, N.O.S. ((S)-(+)-Ketoprofen)

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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

生物活性

S-(+)-Ketoprofen 是 COX-1 和 COX-2 的有效抑制剂，其 IC50 值分别为 1.9 nM 和 27 nM。

酶	IC50 (nM)
COX-1	13 μM
COX-2	370 μM

体外研究

S-(+)-Ketoprofen（化合物 1）是具有强效抑制作用的 COX-1 和 COX-2 抑制剂，其 IC50 值分别为 1.9 nM 和 27 nM。

用途

S-(+)-Ketoprofen 是一种非甾体抗炎药，具有抗炎、镇痛和解热作用。

反应信息

• 作为反应物：
  描述：

  右旋酮洛芬 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 以55%的产率得到(S)-ketoprofenol
  参考文献：
  名称：

  光敏的胸腺嘧啶二聚体通过离域三重态激发态。

  摘要：

  提出了胸腺嘧啶（Thy）二聚体光敏形成的新机理，其中涉及到产生离域三重态激发态是关键步骤。通过将一个二苯甲酮和两个具有不同自由度的Thy单元结合而获得的化学证据支持了这一点，从而将光反应性从纯净的Paternò-Büchi反应切换为完全的化学，区域和立体选择性[2 + 2]环加成反应。

  DOI：

  10.1002/chem.201502719
• 作为产物：
  描述：

  3-(3-benzoyl-phenyl)-2S,3R-dimethyl-oxirane-2-carboxy-5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexane ester 在 sodium carbonate 、 双氧水 、 溶剂黄146 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 10.0h， 以85.6%的产率得到右旋酮洛芬
  参考文献：
  名称：

  一种右旋酮洛芬中间体的合成方法

  摘要：

  本发明属于医药技术领域，具体涉及一种右旋酮洛芬中间体的合成方法，利用Darzens反应的不对称合成制备右旋酮洛芬的中间体，该方法能够提高反应的选择性，降低原料的损耗，提高收率且简化操作流程，有利于实现工业化生产。

  公开号：

  CN109096229A

文献信息

• Eflornithine Prodrugs, Conjugates and Salts, and Methods of Use Thereof
  申请人：Xu Feng

  公开号：US20100120727A1

  公开（公告）日：2010-05-13

  In one aspect, the present invention provides a composition of a covalent conjugate of an eflornithine analog with an anti-inflammatory drug. In another aspect, the present invention provides a composition of an eflornithine prodrug. In another aspect, the present invention provides a composition of an eflornithine or its derivatives aspirin salt. In another aspect, the present invention provides methods for treating or preventing cancer using the conjugates or salts of eflornithine analogs or eflornithine prodrugs.

  在一个方面，本发明提供了一种氟硝西汀类似物与抗炎药物的共价结合物的组合物。在另一个方面，本发明提供了一种氟硝西汀前药的组合物。在另一个方面，本发明提供了一种氟硝西汀或其衍生物水杨酸盐的组合物。在另一个方面，本发明提供了使用氟硝西汀类似物或氟硝西汀前药的共轭物或盐来治疗或预防癌症的方法。
• [EN] MACROCYCLIC COMPOUNDS FOR MODULATING IL-17<br/>[FR] COMPOSÉS MACROCYCLIQUES POUR UNE MODULATION D'IL-17
  申请人：ENSEMBLE THERAPEUTICS CORP

  公开号：WO2013116682A1

  公开（公告）日：2013-08-08

  The invention relates generally to macrocyclic compounds of formula I and their therapeutic use. More particularly, the invention relates to macrocyclic compounds that modulate the activity of IL-17 and/or are useful in the treatment of medical conditions, such as inflammatory diseases and other IL-17-associated disorders.

  这项发明通常涉及公式I的大环化合物及其治疗用途。更具体地，该发明涉及调节IL-17活性的大环化合物，或者用于治疗炎症性疾病和其他与IL-17相关的疾病的大环化合物。
• Palladium‐Catalyzed Asymmetric Markovnikov Hydroxycarbonylation and Hydroalkoxycarbonylation of Vinyl Arenes: Synthesis of 2‐Arylpropanoic Acids
  作者：Ya‐Hong Yao、Xian‐Jin Zou、Yuan Wang、Hui‐Yi Yang、Zhi‐Hui Ren、Zheng‐Hui Guan

  DOI：10.1002/anie.202107856

  日期：2021.10.18

  of carboxylic acids. Herein, we reported the development of a palladium-catalyzed highly enantioselective Markovnikov hydroxycarbonylation of vinyl arenes with CO and water. A monodentate phosphoramidite ligand L6 plays vital role in the reaction. The reaction tolerates a range of functional groups, and provides a facile and atom-economical approach to an array of 2-arylpropanoic acids including several

  不对称羟基羰基化是合成羧酸的最基本但最具挑战性的方法之一。在此，我们报道了钯催化的乙烯基芳烃与 CO 和水的高度对映选择性马尔可夫尼科夫羟基羰基化的发展。单齿亚磷酰胺配体L6反应中起重要作用。该反应耐受一系列官能团，并为一系列 2-芳基丙酸（包括几种常用的非甾体抗炎药）提供了一种简便且原子经济的方法。该催化体系还使乙烯基芳烃与醇发生不对称马尔科夫尼科夫氢烷氧基羰基化反应，得到 2-芳基丙酸酯。机理研究表明，氢化钯是不可逆的，是区域和对映体决定步骤，而水解/醇解可能是限速步骤。
• Enantioselective potential of polysaccharide-based chiral stationary phases in supercritical fluid chromatography
  作者：Gabriela Kucerova、Kveta Kalikova、Eva Tesarova

  DOI：10.1002/chir.22701

  日期：2017.6

  cellulose‐based chiral stationary phase were achieved particularly with propane‐2‐ol and a mixture of isopropylamine and trifluoroacetic acid as organic modifier and additive to CO2, respectively. Methanol and basic additive isopropylamine were preferred on amylose‐based chiral stationary phase. The complementary enantioselectivity of the cellulose‐ and amylose‐based chiral stationary phases allows separation

  使用一组52种分析物在超临界流体色谱中评估了两种基于多糖的手性固定相对手性结构多样的生物活性化合物的对映选择性。固定在2.5μm二氧化硅颗粒上的手性选择剂是纤维素或直链淀粉的三（3,5-二甲基苯基carmabate）衍生物。监测了多糖主链，不同的有机改性剂和不同的流动相添加剂对保留和对映体分离的影响。对于大多数化合物，发现了快速基线对映体分离的条件。纤维素基手性固定相的基线和部分对映体分离的成功率分别为51.9％和15.4％。使用基于直链淀粉的手性固定相，我们获得了76。被测化合物的基线对映体分离率为9％，部分对映体分离率为9.6％。尤其是使用丙烷-2-醇以及异丙胺和三氟乙酸的混合物作为有机改性剂和CO添加剂时，在基于纤维素的手性固定相上获得了最佳结果2个。在基于直链淀粉的手性固定相上，优选甲醇和碱性添加剂异丙胺。纤维素和直链淀粉基手性固定相的互补对映选择性可分离大多数经测试的结构不同的化
• Substrate Evaluation of<i>Rhodococcus erythropolis</i>SET1, a Nitrile Hydrolysing Bacterium, Demonstrating Dual Activity Strongly Dependent on Nitrile Sub-Structure
  作者：Tracey M. Coady、Lee V. Coffey、Catherine O'Reilly、Claire M. Lennon

  DOI：10.1002/ejoc.201403201

  日期：2015.2

  Rhodococcus erythropolis SET1, a novel nitrile hydrolysing bacterial isolate, has been undertaken with 34 nitriles, 33 chiral and 1 prochiral. These substrates consist primarily of β-hydroxy nitriles with varying alkyl and aryl groups at the β position and containing in several compounds different substituents α to the nitrile. In the case of β-hydroxy nitriles without substitution at the α position

  红球菌 SET1 是一种新型腈水解细菌分离株，已使用 34 种腈、33 种手性和 1 种前手性进行了评估。这些底物主要由 β-羟基腈组成，在 β 位具有不同的烷基和芳基，并且在几种化合物中含有与腈不同的 α 取代基。在 α 位没有取代的 β-羟基腈的情况下，由于分离物的腈水解酶活性，酸是获得的主要产物，以及生物转化后回收的腈。出乎意料的是，当 β-羟基腈在该位置具有乙烯基时，发现酰胺是主要的水解产物。为了进一步探索这种行为，评估了在 α 位置包含吸电子基团的其他相关底物，在 SET1 存在下的生物转化过程中也观察到了酰胺。因此，这种新的分离物也证明了对似乎是底物依赖性的腈类的 NHase 活性。