(4-乙氧基苯基)脲 | 150-69-6

• 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: (4-乙氧基苯基)脲
• 中文别名: 对乙氧基苯基脲；4-乙氧基苯基脲；乙氧苯基脲
• 英文名称: N-(p-ethoxyphenyl)urea
• 英文别名: Dulcin；(4-ethoxyphenyl)urea
• CAS: 150-69-6
• 化学式: C₉H₁₂N₂O₂
• mdl: MFCD00025431
• 分子量: 180.206
• InChiKey: GGLIEWRLXDLBBF-UHFFFAOYSA-N

物化性质

• 熔点：
  160-161℃
• 沸点：
  313.03°C (rough estimate)
• 密度：
  1.199
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）
• 最大波长(λmax)：
  289nm(EtOH)(lit.)
• LogP：
  1.005 (est)
• 物理描述：
  Dulcin appears as white crystals. (NTP, 1992)
• 颜色/状态：
  White needle-like crystals or powder
• 味道：
  Very sweet taste, about 250 times as sweet as sugar cane
• 蒸汽压力：
  9.8X10-6 mm Hg at 25 °C (est)
• 分解：
  When heated to decomposition it emits toxic fumes of /oxides of nitrogen/.

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  2

ADMET

代谢

/Dulcin (DL)/ 在兔子口服给药后以尿苷酸-N-葡萄糖苷酸形式排出。... 已经从兔肝中鉴定出七种 /UDP-葡萄糖苷酸转移酶 (UGT)/ 同工酶（UGT1A3、UGT1A4、UGT1A6、UGT1A7、UGT2B13、UGT2B14 和 UGT2B16），但这些 UGT 以 DL 作为底物尚未被研究。在这项工作中，通过使用兔肝微粒体（RabLM）和克隆/表达的兔 UGT 同工酶，研究了催化 DL 葡萄糖苷酸形成的 UGT 同工酶的鉴定。通过使用电喷雾液相色谱-串联质谱法，定量测定了 RabLM 和表达每个 UGT 同工酶的 COS-7 细胞匀浆中 DL-N-葡萄糖苷酸（DNG）的产生。使用 Eadie-Hofstee 图分析 RabLM 中 DNG 形成得到的 Vmax 为 0.911 nM/min/mg 蛋白质，Km 为 1.66 mM。DNG 形成仅由克隆表达的兔 UGT1A7 和 UGT2B16 催化（Vmax 分别为 3.98 和 1.16 pmol/min/mg 蛋白质，Km 分别为 1.23 和 1.69 mM）。辛基没食子酸通过抑制 UGT1A7 证实了 UGT1A7 对 DNG 形成的重要贡献。进一步研究表明辛基没食子酸通过竞争性抑制 RabLM 中的 DNG 生产（Ki = 0.149 mM）。这些结果表明 UGT1A7 是在 RabLM 中催化 DL 的 N-葡萄糖苷酸化的主要同工酶。

... /Dulcin (DL)/ is excreted as a urinary ureido-N-glucuronide after oral administration to rabbits. ... Seven /UDP-glucuronosyltransferase (UGT)/ isoforms (UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT2B13, UGT2B14, and UGT2B16) have been identified from rabbit liver, but these UGTs have not been investigated using DL as a substrate. In this work, the identities of UGT isoforms catalyzing the formation of DL glucuronide were investigated using rabbit liver microsomes (RabLM) and cloned/expressed as rabbit UGT isoforms. DL-N-glucuronide (DNG) production was determined quantitatively in RabLM and homogenates of COS-7 cells expressing each UGT isoform by using electrospray liquid chromatography-tandem mass spectrometry. Analysis of DNG formation using RabLM, by Eadie-Hofstee plot, gave a Vmax of 0.911 nM/min/mg protein and the Km of 1.66 mM. DNG formation was catalyzed only by cloned expressed rabbit UGT1A7 and UGT2B16 (Vmax of 3.98 and 1.16 pmol/min/mg protein and a Km of 1.23 and 1.69 mM, respectively). Substrate inhibition of UGT1A7 by octylgallate confirmed the significant contribution of UGT1A7 to the formation of DNG. Octylgallate was further shown to competitively inhibit DNG production by RabLM (Ki = 0.149 mM). These results demonstrate that UGT1A7 is the major isoform catalyzing the N-glucuronidation of DL in RabLM.

来源:Hazardous Substances Data Bank (HSDB)

代谢

... Dulcin（DL）含有一个脲基团，该基团在兔肝微粒体中通过直接葡萄糖醛酸化代谢。...使用人肝微粒体（HLM）和表达的human UDP-葡萄糖醛酸基转移酶（UGT）酶对DL的葡萄糖醛酸化进行了研究。九个HLM样本的平均K（m）和V（max）值分别为2.10 mM和0.156 nmol/mg/min。在筛选出能够进行DL葡萄糖醛酸化的六种人UGT同种型中，只有UGT1A1和UGT1A9显示出活性。使用UGT1A1和UGT1A9的表观K（m）值分别为5.06和6.99 mM，表观V（max）值分别为0.0461和0.106 nmol/min/mg。UGT1A9的底物酚酞以竞争性方式抑制HLM中的DL葡萄糖醛酸化（K（i）= 0.356 mM），而UGT1A1的底物胆红素则没有。这些结果表明UGT1A9是催化DL葡萄糖醛酸化的关键酶。

... Dulcin (DL) possesses an ureido group that is metabolized by direct glucuronidation in rabbit liver microsomes. ...The glucuronidation of DL was studied using human liver microsomes (HLM) and expressed human UDP-glucuronosyltransferase (UGT) enzymes. The average K (m) and V (max) values from nine HLM samples were 2.10 mM and 0.156 nmol/mg/min, respectively. Of the six human UGT isoforms screened for their ability to glucuronidate DL, only UGT1A1 and UGT1A9 showed activity. The apparent K (m) values using UGT1A1 and UGT1A9 were 5.06 and 6.99 mM, and the apparent V (max) values were 0.0461 and 0.106 nmol/min/mg, respectively. Phenolphthalein, a substrate for UGT1A9, inhibited DL glucuronidation in HLM competitively (K (i) = 0.356 mM), but bilirubin, a substrate for UGT1A1, did not. These results suggest that UGT1A9 is a key enzyme catalyzing the glucuronidation of DL.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在处理的兔子的尿液中，发现了3%的杜尔辛剂量未改变地被排出，27%以杜尔辛N-葡萄糖苷酸的形式排出，另外40%以对-羟基苯脲及其O-硫酸盐和O-葡萄糖苷酸的形式共同排出，还有少量的尿中对-氨基酚。

/It was/ found that 3% of a dose of dulcin was excreted unchanged in the urine of treated rabbits, 27% was excreted as dulcin N-glucuronide, a further 40% was excreted collectively as para-hydroxyphenylurea and its O-sulphate and O-glucuronide, and there were small amounts of urinary para-aminophenol.

来源:Hazardous Substances Data Bank (HSDB)

代谢

Dulcin 已知的人类代谢物包括 (2S,3S,4S,5R)-6-[(4-乙氧基苯基)碳酰胺氨基]-3,4,5-三羟基氧杂环己烷-2-羧酸。

Dulcin has known human metabolites that include (2S,3S,4S,5R)-6-[(4-ethoxyphenyl)carbamoylamino]-3,4,5-trihydroxyoxane-2-carboxylic acid.

来源:NORMAN Suspect List Exchange

毒理性

• 致癌物分类

国际癌症研究机构致癌剂：杜尔辛

IARC Carcinogenic Agent:Dulcin

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：第3组：无法归类其对人类致癌性

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第12卷：（1976年）一些氨基甲酸酯、硫代氨基甲酸酯和脒脲

IARC Monographs:Volume 12: (1976) Some Carbamates, Thiocarbamates and Carbazides

来源:International Agency for Research on Cancer (IARC)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练进行。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗救助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠口服后，二氯苯胺迅速被吸收并分布到全身，肝脏、肾脏、大脑和肺部含量最高；在给药后24小时内，组织水平降低到十分之一。

After its oral administration to rats, dulcin is absorbed rapidly and is distributed throughout the body, with highest concentrations in the liver, kidneys, brain and lungs; tissue levels diminished to one-tenth within 24 hours after dosing.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2924299090
• 危险性防范说明：
  P264,P280,P302+P352+P332+P313+P362+P364,P305+P351+P338+P337+P313
• 危险性描述：
  H315,H319
• 储存条件：
  表中的温度范围是 0-6℃。

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: N-(4-Ethoxyphenyl)urea
Synonyms:

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

---

Section 3. Composition/information on ingredients.
Ingredient name: N-(4-Ethoxyphenyl)urea
CAS number: 150-69-6

---

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.

---

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.

---

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.

---

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:

---

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.

---

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: C9H12N2O2
Molecular weight: 180.2

---

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.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

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.

---

Section 14. Transportation information
Non-harzardous for air and ground transportation.

---

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.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  (4-乙氧基苯基)脲 在 盐酸 、 乙醇 、 sodium ethanolate 作用下， 生成 1-(4-乙氧基苯基)-2,4,6(1H,3H,5H)-嘧啶三酮
  参考文献：
  名称：

  Ridi, Annali di Chimica, 1952, vol. 42, p. 25,29

  摘要：

  DOI：
• 作为产物：
  描述：

  N-(4-乙氧基苯基)氨基甲酸乙酯 在 氨 作用下， 生成 (4-乙氧基苯基)脲
  参考文献：
  名称：

  DE77420

  摘要：

  公开号：

文献信息

• [EN] AMINO ACID DERIVATIVES AND THEIR USE AS FLAVOR MODIFIERS<br/>[FR] DÉRIVÉS D'ACIDES AMINÉS ET LEUR UTILISATION EN TANT QUE MODIFICATEURS DE GOÛT
  申请人：FIRMENICH & CIE

  公开号：WO2021209345A1

  公开（公告）日：2021-10-21

  The present invention provides derivatives of glutamine of formula (I) and derivatives of arginine of formula (II), and the use of such compounds as flavor modifiers. The invention further provides the use of such derivatives of glutamine and arginine to enhance the salty and umami taste of ingestible compositions as ingestible compositions that include such derivatives of glutamine and arginine and bulking agents.

  本发明提供了公式(I)的谷氨酰衍生物和公式(II)的精氮酸衍生物，以及将这些化合物用作风味调节剂的用途。该发明进一步提供了利用这些谷氨酰和精氮酸衍生物增强可摄入组合物的咸味和鲜味的用途，作为包含这些谷氨酰和精氮酸衍生物以及增稠剂的可摄入组合物。
• MODULATION OF CHEMOSENSORY RECEPTORS AND LIGANDS ASSOCIATED THEREWITH
  申请人：Tachdjian Catherine

  公开号：US20080306053A1

  公开（公告）日：2008-12-11

  The present invention provides screening methods for identifying modifiers of chemosensory receptors and their ligands, e.g., by determining whether a test entity is suitable to interact with one or more interacting sites within the Venus flytrap domains of the chemosensory receptors as well as modifiers capable of modulating chemosensory receptors and their ligands.

  本发明提供了用于识别化学感受受体及其配体的修饰因子的筛选方法，例如，通过确定测试实体是否适合与化学感受受体的捕蝇草结构域内的一个或多个相互作用位点发生相互作用，以及能够调节化学感受受体及其配体的修饰因子。
• BITTER TASTE MODIFIERS INCLUDING SUBSTITUTED 1-BENZYL-3-(1-(ISOXAZOL-4-YLMETHYL)-1H-PYRAZOL-4-YL)IMIDAZOLIDINE-2,4-DIONES AND COMPOSITIONS THEREOF
  申请人：SENOMYX, INC.

  公开号：US20160376263A1

  公开（公告）日：2016-12-29

  The present invention includes compounds and compositions known to modify the perception of bitter taste, and combinations of said compositions and compounds with additional compositions, compounds, and products. Exemplary compositions comprise one or more of the following: cooling agents; inactive drug ingredients; active pharmaceutical ingredients; food additives or foodstuffs; flavorants, or flavor enhancers; food or beverage products; bitter compounds; sweeteners; bitterants; sour flavorants; salty flavorants; umami flavorants; plant or animal products; compounds known to be used in pet care products; compounds known to be used in personal care products; compounds known to be used in home products; pharmaceutical preparations; topical preparations; cannabis-derived or cannabis-related products; compounds known to be used in oral care products; beverages; scents, perfumes, or odorants; compounds known to be used in consumer products; silicone compounds; abrasives; surfactants; warming agents; smoking articles; fats, oils, or emulsions; and/or probiotic bacteria or supplements.

  本发明涵盖已知用于改变苦味感知的化合物和组合物，以及所述组合物和化合物与额外的组合物、化合物和产品的组合。示例组合物包括以下一种或多种：冷却剂；无活性药物成分；活性药用成分；食品添加剂或食品；调味剂或调味增强剂；食品或饮料产品；苦味化合物；甜味剂；苦味剂；酸味调味剂；咸味调味剂；鲜味调味剂；植物或动物产品；已知用于宠物护理产品中的化合物；已知用于个人护理产品中的化合物；已知用于家用产品中的化合物；制药制剂；局部制剂；大麻衍生或与大麻相关的产品；已知用于口腔护理产品中的化合物；饮料；香味、香水或除臭剂；已知用于消费品中的化合物；硅化合物；磨料；表面活性剂；发热剂；吸烟物品；脂肪、油脂或乳化剂；和/或益生菌或补充剂。
• [EN] IDO INHIBITORS<br/>[FR] INHIBITEURS DE L'IDO
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2014150646A1

  公开（公告）日：2014-09-25

  There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or autoimmune diseases utilizing the compounds of the invention. Formula (I).

  已披露的化合物可调节或抑制色胺酸2,3-二氧化酶（IDO）的酶活性，含有该化合物的药物组合物以及利用本发明的化合物治疗增殖性疾病，如癌症、病毒感染和/或自身免疫疾病的方法。公式（I）。
• Synthesis and Studies of New 2-(Coumarin-4-yloxy)-4,6-(substituted)-s-Triazine Derivatives as Potential Anti-HIV Agents
  作者：Dharmesh H. Mahajan、Christophe Pannecouque、Erik De Clercq、Kishor H. Chikhalia

  DOI：10.1002/ardp.200800149

  日期：2009.5

  Novel 2‐(coumarin‐4‐yloxy)‐4,6‐(substituted)‐s‐triazine derivatives i. e., diaryltriazine (DATA) are reported as novel non‐nucleoside reverse transcriptase inhibitors (NNRTIs), were synthesized and their activities against human immunodeficiency virus HIV‐1 (III‐B), HIV‐2 (ROD), and the double RT mutant HIV‐1 (K103N and Y181C) were assessed. Modifications at positions 4 and 6 of the coumarinyl‐triazine

  合成了新型 2-(香豆素-4-yloxy)-4,6-(取代)-s-三嗪衍生物，即二芳基三嗪 (DATA) 作为新型非核苷逆转录酶抑制剂 (NNRTIs)，并合成了它们对人类的活性评估了免疫缺陷病毒 HIV-1 (III-B)、HIV-2 (ROD) 和双 RT 突变体 HIV-1（K103N 和 Y181C）。与奈韦拉平和依法韦仑相比，香豆素基三嗪支架的第 4 和 6 位的修饰产生了有趣的衍生物，对选定的 HIV 毒株显示出良好至中等的抗 HIV 活性。合成的化合物通过FTIR、1H-NMR和质谱数据以及元素分析进行​​表征。

表征谱图