苯乙酰脲 | 63-98-9

• 物质功能分类: 原料药 - 神经系统用药 - 抗癫痫及抗惊厥药
• 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: 苯乙酰脲
• 英文名称: phenacemide
• 英文别名: phenylacetyl urea；N-carbamoyl-2-phenylacetamide
• CAS: 63-98-9
• 化学式: C₉H₁₀N₂O₂
• 分子量: 178.191
• InChiKey: XPFRXWCVYUEORT-UHFFFAOYSA-N

物化性质

• 熔点：
  214-216 °C
• 沸点：
  310.41°C (rough estimate)
• 密度：
  1.2221 (rough estimate)
• 物理描述：
  Solid
• 颜色/状态：
  CRYSTALS FROM ALCOHOL
• 气味：
  ODORLESS, OR PRACTICALLY SO
• 味道：
  TASTELESS
• 溶解度：
  10.2 g/L
• 稳定性/保质期：
  Commercially available phenacemide tablets have an expiration date of 5 years following the data of manufacture.
• 分解：
  When heated to decomposition it emits toxic fumes of NOx.
• 碰撞截面：
  128.3 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]
• 保留指数：
  1473

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  72.2
• 氢给体数：
  2
• 氢受体数：
  2

ADMET

代谢

在肝脏通过肝微粒体酶代谢，通过p-羟基化作用被灭活。

Metabolized in the liver by hepatic microsomal enzymes, where it is inactivated by p-hydroxylation.

来源:DrugBank

代谢

兔体内对对乙酰氨基苯乙酰胺的生物转化产生了苯乙酸和苯乙脲酸，这是通过脲基的水解，以及通过酚羟基的连续环羟基化和甲基化产生了4-羟基对乙酰氨基苯乙酰胺和3-甲氧基-4-羟基对乙酰氨基苯乙酰胺。对乙酰氨基苯乙酰胺N-葡萄糖苷酸...似乎没有形成...

BIOTRANSFORMATION OF PHENACETYLUREA IN RABBITS GAVE PHENYLACETIC ACID & PHENACETURIC ACID BY HYDROLYSIS OF UREIDO-GROUP, & 4-HYDROXYPHENACETYLUREA & 3-METHOXY-4-HYDROXYPHENACETYLUREA BY SUCCESSIVE RING-HYDROXYLATION & METHYLATION OF PHENOLIC HYDROXY-GROUP. PHENACETYLUREA N-GLUCURONIDE...DID NOT APPEAR TO BE FORMED...

来源:Hazardous Substances Data Bank (HSDB)

代谢

肝脏微粒体酶的生物转化，包括通过酚羟基化使苯基取代基失活；环闭合形成海因环并不会发生。

BIOTRANSFORMATION BY HEPATIC MICROSOMAL ENZYMES INCL INACTIVATION BY PARAHYDROXYLATION OF PHENYL SUBSTITUENT; RING CLOSURE TO FORM HYDANTOIN DOES NOT OCCUR.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在肝脏由肝微粒体酶代谢，通过p-羟基化作用失活。半衰期：22-25小时。

Metabolized in the liver by hepatic microsomal enzymes, where it is inactivated by p-hydroxylation. Half Life: 22-25 hours.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

Phenacemide binds to and blocks neuronal sodium channels or voltage sensitive calcium channels. This blocks or suppresses neuronal depolarization and hypersynchronization. Hypersynchronization is what often causes seizures. phenacemide与神经钠通道或电压敏感钙通道结合并阻断。这会阻止或抑制神经去极化和超同步。超同步常常是导致癫痫的原因。

Phenacemide binds to and blocks neuronal sodium channels or voltage sensitive calcium channels. This blocks or suppresses neuronal depolarization and hypersynchronization. Hypersynchronization is what often causes seizures.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

可能会导致一种潜在的危险性皮疹，这种皮疹可能会发展成史蒂文斯-约翰逊综合症，这是一种极其罕见但可能致命的皮肤病。

May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

几乎完全被吸收。

Almost completely absorbed.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性数据

LD50: 987 mg/kg（口服，小鼠）（A308） LD50: 2500 mg/kg（口服，兔）（A308） LD50: 1600 mg/kg（口服，大鼠）（A308）

LD50: 987 mg/kg (Oral, Mouse) (A308) LD50: 2500 mg/kg (Oral, Rabbit) (A308) LD50: 1600 mg/kg (Oral, Rat) (A308)

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

• 吸收

几乎完全被吸收。

Almost completely absorbed.

来源:DrugBank

吸收、分配和排泄

苯乙酰胺几乎完全通过胃肠道吸收。未改变的药物不会通过尿液排出。与疗效和安全性相关的血药浓度尚未确定。

PHENACEMIDE IS ALMOST COMPLETELY ABSORBED FROM GI TRACT. ... UNCHANGED DRUG IS NOT EXCRETED IN URINE... PLASMA CONCN ASSOCIATED WITH EFFICACY & SAFETY HAVE NOT BEEN ESTABLISHED.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

比较不同物种对(14)C-对乙酰氨基酚的排泄显示在生物转化方面的差异。口服给药后，大鼠在48小时内的尿液中排出了63%的(14)C，豚鼠排出56%，家兔排出87%，而小鼠排出62%。

COMPARISON OF EXCRETION OF (14)C-PHENACETYLUREA IN DIFFERENT SPECIES SHOWED DIFFERENCES IN BIOTRANSFORMATION. AFTER ORAL DOSE, RATS EXCRETED 63% OF (14)C IN 48-HR URINE, GUINEA-PIGS 56%, RABBITS 87%, & MICE 62%.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn
• 危险类别码：
  R22
• 海关编码：
  29242998
• 储存条件：
  本品应密封存放在阴凉干燥、避免光照的地方保存。

SDS

Name:	Phenylacetylurea Material Safety Data Sheet
Synonym:	Phenarone; Carbamide Phenylacetate; Cetylureum; Phenicarb
CAS:	63-98-9

Section 1 - Chemical Product MSDS Name:Phenylacetylurea Material Safety Data Sheet
Synonym:Phenarone; Carbamide Phenylacetate; Cetylureum; Phenicarb

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
63-98-9	Phenacemide	ca 100	200-570-2

Hazard Symbols: XN
Risk Phrases: 22

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Harmful if swallowed.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation.
Ingestion:
May cause irritation of the digestive tract. May cause central nervous system depression. May be harmful if swallowed. Ingestion of very large amounts may cause generalized depression, headache, and drowsiness.
Inhalation:
May cause respiratory tract irritation. Exposure produces central nervous system depression.
Chronic:
Adverse reproductive effects have been reported in animals.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse.
Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion. Use extinguishing media appropriate to the surrounding fire. Substance is noncombustible.
Extinguishing Media:
Substance is noncombustible; use agent most appropriate to extinguish surrounding fire. Use agent most appropriate to extinguish fire. Use water spray, dry chemical, carbon dioxide, or appropriate foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Use with adequate ventilation. Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances. Do not exceed 30C (86F).

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 63-98-9: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Crystalline powder
Color: white
Odor: practically odorless
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 214.00 - 216.00 deg C
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water: Slightly soluble.
Specific Gravity/Density:
Molecular Formula: C9H10N2O2
Molecular Weight: 178.19

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, dust generation, excess heat, strong oxidants, temperatures above 40C.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, irritating and toxic fumes and gases, carbon dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 63-98-9: YU0875000 LD50/LC50:
CAS# 63-98-9: Oral, mouse: LD50 = 987 mg/kg; Oral, rabbit: LD50 = 2500 mg/kg; Oral, rat: LD50 = 1600 mg/kg.
Carcinogenicity:
Phenacemide - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XN
Risk Phrases:
R 22 Harmful if swallowed.
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
S 28A After contact with skin, wash immediately with
plenty of water.
S 37 Wear suitable gloves.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 63-98-9: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 63-98-9 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 63-98-9 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生产方法：

1. 以硫脲和水合肼为原料进行加热反应制得。

2. 先将水合肼与硫酸配制成硫酸肼，再与硫氰酸铵反应生成硫氰酸肼，接着与乙醛反应后经水解得到氨基硫脲。

反应信息

• 作为反应物：
  描述：

  苯乙酰脲 在 乙醇 、 copper oxide-chromium oxide 作用下， 120.0 ℃ 、14.71 MPa 条件下， 生成 1-[2]furyl-heptan-3-ol
  参考文献：
  名称：

  Til' et al., Zhurnal Obshchei Khimii, 1957, vol. 27, p. 110,111, 112; engl. Ausg. S. 125, 127

  摘要：

  DOI：
• 作为产物：
  描述：

  phenylacetyl-carbamoyl chloride 在 氨 作用下， 以 乙醚 为溶剂， 反应 0.5h， 生成 苯乙酰脲
  参考文献：
  名称：

  Sidky, M. M.; El-Kateb, A. A.; Mahran, M. R., Phosphorus and Sulfur and the Related Elements, 1987, vol. 29, p. 11 - 16

  摘要：

  DOI：

文献信息

• 1-(2-PHENOXYMETHYLHETEROARYL)PIPERIDINE AND PIPERAZINE COMPOUNDS
  申请人：Stangeland Eric L.

  公开号：US20110230495A1

  公开（公告）日：2011-09-22

  The invention relates to compounds of formula I: where X, HAr, a, and R 1 through R 6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds of formula I are serotonin and norepinephrine reuptake inhibitors. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

  本发明涉及如下公式I的化合物： 其中X，HAr，a，以及R1至R6如说明书所述，或其药用可接受的盐。公式I的化合物是5-羟色胺和去甲肾上腺素再摄取抑制剂。本发明还涉及包含这些化合物的药物组合物；使用这些化合物的方法；以及制备这些化合物的方法和中间体。
• [EN] BUPRENORPHINE ANALOGS<br/>[FR] ANALOGUES DE BUPRÉNORPHINE
  申请人：PURDUE PHARMA LP

  公开号：WO2012038813A1

  公开（公告）日：2012-03-29

  The present invention is directed to Buprenorphine Analog compounds of the Formula (I), Formula (IA) or Formula (IB) shown below, wherein R1, R2, R8, R 3a, R 3b, G, X, Z and Y are as defined herein. Compounds of the Invention are useful for treating pain, constipation, and other conditions modulated by activity of opioid and ORL-1 receptors.

  本发明涉及如下所示的公式(I)、公式(IA)或公式(IB)的丁丙诺啡类似物化合物，其中R1、R2、R8、R 3a、R 3b、G、X、Z和Y的定义如本文所述。本发明的化合物可用于治疗疼痛、便秘以及通过阿片类和ORL-1受体的活性调节的其他状况。
• PYRIDINE AND PIPERIDINE DERIVATIVES AND USE THEREOF
  申请人：Purdue Pharma L.P.

  公开号：US20150141434A1

  公开（公告）日：2015-05-21

  The invention provides compounds that are useful as sodium channel blockers. In one aspect, the invention provides compounds of Formula I: or pharmaceutically acceptable salts, solvates, hydrates, or diastereomers thereof, wherein R 1 , R 4 , X, G, n, p, W 1 , W 2 , W 3 , W 4 , and the E ring are defined in the disclosure. In certain embodiments, the invention provides compounds of Formulae II-XIII as set forth supra. The invention also provides the use of compounds of any of the above discussed formulae to treat a disorder responsive to blockade of sodium channels. In one embodiment, Compounds of the Invention are useful for treating pain.

  本发明提供了一种用作钠通道阻断剂的化合物。在一方面，本发明提供了公式I的化合物： 或其药用可接受的盐、溶剂化物、水合物或对映异构体，其中R1、R4、X、G、n、p、W1、W2、W3、W4和E环在公开中定义。在某些实施例中，本发明提供了上述公式II-XIII的化合物。本发明还提供了使用上述任何讨论公式的化合物来治疗对钠通道阻断有反应的疾病。在一个实施例中，发明化合物用于治疗疼痛。
• 2,5-DIALKYL-4-H/HALO/ETHER-PHENOL COMPOUNDS
  申请人：Tansna Therapeutics Inc.

  公开号：US20150148430A1

  公开（公告）日：2015-05-28

  The present disclosure provides phenolic compounds useful in the treatment of neurological conditions such as convulsions and tremors, having the structure of Formula (I): wherein R 2 , R 4 , & R 5 , are as defined in the detailed description; pharmaceutical compositions comprising at least one of the compounds; and methods for treating neurological conditions.

  本公开提供用于治疗诸如惊厥和震颤等神经学状况的酚类化合物，其具有公式（I）的结构： 其中R2、R4和R5如详细描述中定义；包含至少一种该化合物的药物组合物；以及用于治疗神经学状况的方法。
• [EN] SMALL MOLECULE C-MYC INHIBITORS<br/>[FR] PETITES MOLÉCULES INHIBITRICES DE C-MYC
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2015089180A1

  公开（公告）日：2015-06-18

  This invention provides small molecule Myc-inhibitors. Also provided in the invention are therapeutic applications of these compounds for treating Myc-driven cancer and other related methods.

  这项发明提供了小分子Myc抑制剂。该发明还提供了这些化合物的治疗应用，用于治疗Myc驱动的癌症和其他相关方法。

表征谱图