sodium phenylacetate | 114-70-5

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物 - 羧酸酯及其衍生物的盐
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: sodium phenylacetate
• 英文别名: sodium 2-phenylacetate；phenylacetic acid sodium salt；sodium;2-phenylacetate
• CAS: 114-70-5
• 化学式: C₈H₇O₂*Na
• 分子量: 158.132
• InChiKey: HZOREEUASZHZBI-UHFFFAOYSA-M

物化性质

• 沸点：
  265.5℃[at 101 325 Pa]
• 密度：
  1.164[at 20℃]
• LogP：
  -2.016 at 25℃
• 颜色/状态：
  Aqueous solution is pale yellow
• 溶解度：
  In water, 1X10+6 mg/L at 25 °C (est)
• 分解：
  When heated to decomposition it emits acrid smoke and irritating vapors.
• 稳定性/保质期：

  遇明火或高温时可燃，燃烧会产生具有刺激性的氧化钠烟雾。

计算性质

• 辛醇/水分配系数(LogP)：
  -3.02
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  40.1
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

苯乙酸与谷氨酰胺在肝脏和肾脏结合形成苯乙酰谷氨酰胺，通过乙酰化反应。苯乙酰谷氨酰胺通过肾脏的肾小球滤过和肾小管分泌被排出体外。苯乙酰谷氨酰胺每摩尔含有的氮量与尿素相同（两者都含有2摩尔的氮）...

Phenylacetate conjugates with glutamine in the liver and kidneys to form phenylacetylglutamine, via acetylation. Phenylacetylglutamine is excreted by the kidneys via glomerular filtration and tubular secretion. The nitrogen content of phenylacetylglutamine per mole is identical to that of urea (both contain 2 moles of nitrogen). ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

苯乙酸和苯甲酸的代谢速率存在差异。从苯甲酸形成马尿酸的过程比从苯乙酸形成苯乙酰谷氨酰胺的过程要快，而且马尿酸的排出速率似乎也比苯乙酰谷氨酰胺的排出速率要快。

A difference in the metabolic rates for phenylacetate and benzoate was noted. The formation of hippurate from benzoate occurred more rapidly than that of phenylacetylglutamine from phenylacetate, and the rate of elimination for hippurate appeared to be more rapid than that for phenylacetylglutamine.

来源:Hazardous Substances Data Bank (HSDB)

代谢

苯乙酸和苯甲酸钠在肝脏中代谢。

Sodium phenylacetate and sodium benzoate are metabolized in the liver.

来源:Hazardous Substances Data Bank (HSDB)

代谢

苯乙酸钠和苯甲酸钠在肾脏中代谢，其代谢物苯乙酰谷氨酰胺（苯乙酸钠的代谢物）和马尿酸（苯甲酸钠的代谢物）主要通过尿液排出。

Sodium phenylacetate and sodium benzoate are metabolized in the kidney and phenylacetylglutamine (metabolite of sodium phenylacetate) and hippuric acid (metabolite of sodium benzoate) are mainly excreted in urine.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

丙戊酸被报告通过抑制N-乙酰谷氨酸，即碳酐磷酸化合酶的辅因子，引发高氨血症。丙戊酸与苯乙酸钠和苯甲酸钠的合并使用可能会加剧尿素循环障碍，并拮抗氨解毒剂降低血氨的效果。

Valproic acid has been reported to induce hyperammonemia via inhibition of N-acetylglutamate, a cofactor for carbamyl phosphate synthetase. Concomitant use of valproic acid with sodium phenylacetate and sodium benzoate may exacerbate urea cycle disorders and antagonize plasma ammonia lowering effects of the ammonia detoxicant.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

一些抗感染药物（例如，青霉素）可能会与苯乙酰谷氨酰胺和苯乙酰脲竞争活性肾小管分泌，影响药物分布。

Some anti-infective agents (e.g., penicillin) may compete with phenylacetylglutamine and hippurate for active renal tubular secretion, affecting drug disposition.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

丙磺舒抑制肾脏对有机化合物的转运（包括氨基酸酸），可能会影响肾脏对苯乙酰谷氨酰胺和苯乙酰尿的排泄。

Probenecid inhibits renal transport of organic compounds (including aminohippuric acid), and may affect renal excretion of phenylacetylglutamine and hippurate.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

苯乙酸钠（NaPA）已被证明与视黄酸（RA）在诱导人类神经母细胞瘤细胞分化方面具有协同作用。我们的研究表明，NaPA可以通过上调核视黄酸受体-β（RAR β）的表达影响RA的分化程序。研究者们发现，NaPA并不改变RAR β mRNA的半衰期；因此，mRNA水平的增加稳定性并不有助于NaPA的诱导。相反，NaPA能够特异性激活一个报告基因构建体（delta SV β RE-CAT），该构建体包含一个位于RAR β启动子中的视黄酸反应元件（RARE β）。在共转染核视黄酸受体表达载体的神经母细胞瘤细胞中，NaPA也能激活delta SV β RE-CAT，这表明这种激活独立于细胞RAR水平。综上所述，我们的发现表明，NaPA对RAR β的诱导在转录水平上进行调节，并通过视黄酸反应元件RARE β介导。这种效应可能是NaPA和RA在促进神经母细胞瘤分化方面强烈协同作用的部分原因。

Sodium phenylacetate (NaPA) has been shown to synergize with retinoic acid (RA) in inducing the differentiation of human neuroblastoma cells. Our studies indicated that NaPA can impact on the RA differentiation program by upregulating nuclear retinoic acid receptor-beta (RAR beta) expression. /Investigators/ have found that NaPA does not alter the half-life of RAR beta mRNA; thus, increased stability of mRNA levels does not contribute to NaPA induction. In contrast, NaPA was able to specifically activate a reporter gene construct (delta SV beta RE-CAT) which contains a retinoic acid response element (RARE beta) that is located in the RAR beta promoter. Activation of delta SV beta RE-CAT by NaPA also occurred in neuroblastoma cells cotransfected with a nuclear retinoic acid receptor expression vector, demonstrating the independence of this activation on cellular RAR levels. Taken together, our findings suggest that induction of RAR beta by NaPA is regulated at the level of transcription and mediated through the retinoic acid response element, RARE beta. This effect may account, at least in part, for the strong synergy between NaPA and RA in promoting neuroblastoma differentiation.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

识别和使用：苯乙酸钠在水中溶液呈淡黄色。它被用作生产青霉素G的前体；生产作为杀菌剂的重金属盐的中介。与苯甲酸钠联合用于治疗急性高血氨症和尿素循环酶缺乏患者的相关脑病。人体研究：苯乙酸钠和苯甲酸钠通过作为排泄废物氮的尿素替代物来降低氨浓度。苯乙酸与肝脏和肾脏中的谷氨酰胺结合形成苯乙酰谷氨酰胺，苯甲酸与甘氨酸结合形成马尿酸；随后苯乙酰谷氨酰胺和马尿酸通过尿液排出。在苯乙酸钠和苯甲酸钠治疗期间有过量报告。这些患者的死亡原因包括心肺衰竭/停止（6名患者），高血氨症（3名患者），颅内压增高（2名患者），伴感染性休克和凝血病肺炎（1名患者），透析程序错误（1名患者），呼吸衰竭（1名患者），顽固性低血压和可能的败血症（1名患者），以及未知原因（1名患者）。此外，其他中毒迹象可能包括意识模糊（无高血氨症情况下），过度换气，严重代偿性代谢性酸中毒，可能有呼吸成分，大阴离子间隙，高钠血症和高渗透压，进行性脑病，心血管崩溃。在接受苯乙酸钠和苯甲酸钠治疗的患者中，6%或更多的患者出现的副作用包括呕吐，高血糖，低钾血症，癫痫发作和智力障碍。在接受静脉注射苯乙酸的癌症患者中报告了神经毒性副作用（主要是嗜睡，疲劳，头晕）。较少见的是，头痛，味觉障碍，听力下降，定向障碍，记忆受损和现有神经病的加重。这些效果（主要是轻微的）在治疗开始时急性发作，并在停药后可逆。此外，苯乙酸钠和苯甲酸钠可能会通过在患有高胆红素血症的新生儿中将胆红素从白蛋白中移位，从而增加间接高胆红素血症的风险。动物研究：没有数据可用。

IDENTIFICATION AND USE: Sodium phenylacetate is pale yellow in aqueous solution. It is used as a precursor in production of penicillin G; intermediate for producing heavy metal salts which act as fungicides. Used with sodium benzoate for the treatment of acute hyperammonemia and associated encephalopathy in patients with deficiencies in enzymes of the urea cycle. HUMAN STUDIES: Sodium phenylacetate and sodium benzoate decrease ammonia concentrations by serving as alternatives to urea for the excretion of waste nitrogen. Phenylacetate is conjugated with glutamine in the liver and kidneys to form phenylacetylglutamine, and benzoate is conjugated with glycine to form hippuric acid; phenylacetylglutamine and hippuric acid subsequently are excreted in urine. Overdosage has been reported during sodium phenylacetate and sodium benzoate treatment. Causes of death in these patients included cardiorespiratory failure/arrest (6 patients), hyperammonemia (3 patients), increased intracranial pressure (2 patients), pneumonitis with septic shock and coagulopathy (1 patient), error in dialysis procedure (1 patient), respiratory failure (1 patient), intractable hypotension and probable sepsis (1 patient), and unknown (1 patient). Additionally, other signs of intoxication may include obtundation (in the absence of hyperammonemia), hyperventilation, a severe compensated metabolic acidosis, perhaps with a respiratory component, large anion gap, hypernatremia and hyperosmolarity, progressive encephalopathy, cardiovascular collapse. Adverse effects occurring in 6% or more of patients receiving sodium phenylacetate and sodium benzoate include vomiting, hyperglycemia, hypokalemia, seizures, and mental impairment. Adverse neurotoxic effects (principally somnolence, fatigue, lightheadedness) have been reported in cancer patients receiving iv phenylacetate (250-300 mg/kg daily for 14 days, repeated at 4-week intervals). Less frequently, headache, dysgeusia, hypoacusis, disorientation, impaired memory, and exacerbation of existing neuropathy were reported. Acute onset of these effects (which were mainly mild) occurred upon initiation of such therapy and were reversible upon discontinuance of the drug. In addition, sodium phenylacetate and sodium benzoate may increase the risk of indirect hyperbilirubinemia by displacing bilirubin from albumin in neonates with hyperbilirubinemia. ANIMAL STUDIES: There are no data available.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

静脉给药的苯乙酸和苯甲酸钠在健康成年志愿者中的药代动力学特性得到了表征。苯甲酸和苯乙酸都表现出非线性动力学。在90分钟的静脉输注后，苯甲酸的均值AUC(最后)分别为20.3、114.9、564.6、562.8和1599.1 ug/mL，对应的剂量为1、2、3.75、4和5.5 g/平方米。总清除率从5.19降低到3.62 L/h/平方米，对应的剂量分别为3.75和5.5 g/平方米。

The pharmacokinetics of intravenously administered sodium phenylacetate and sodium benzoate were characterized in healthy adult volunteers. Both benzoate and phenylacetate exhibited nonlinear kinetics. Following 90 minute intravenous infusion mean AUC(last) for benzoate was 20.3, 114.9, 564.6, 562.8, and 1599.1 ug/mL following doses of 1, 2, 3.75, 4, and 5.5 g/sq m, respectively. The total clearance decreased from 5.19 to 3.62 L/h/sq m at the 3.75 and 5.5 g/sq m doses, respectively.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

... 对乙酰苯酚在首次剂量方案后表现出非线性动力学。在1、2、3.75、4和5.5克/平方米的剂量下，AUC(最后)分别为175.6、713.8、2040.6、2181.6和3829.2微克/小时/毫升。总清除率随着剂量的增加从1.82降低到0.89微克/小时/毫升（分别为3.75和4克/平方米）。在90分钟首次输注后接着24小时维持输注的过程中，对乙酰苯酚在输注结束时在血浆中被检测到（3.75克/平方米时Tmax为2小时），而苯甲酸浓度迅速下降（3.75克/平方米时Tmax为1.5小时），在3.75和4克/平方米剂量后的14和26小时分别无法检测到。

... Phenylacetate exhibited nonlinear kinetics following the priming dose regimens. AUC(last) was 175.6, 713.8, 2040.6, 2181.6, and 3829.2 ug/hr/mL following doses of 1, 2, 3.75, 4, and 5.5 g/sq m, respectively. The total clearance decreased from 1.82 to 0.89 ug/hr/mL with increasing dose (3.75 and 4 g/sq m, respectively). During the sequence of 90 minute priming infusion followed by a 24 hour maintenance infusion, phenylacetate was detected in the plasma at the end of infusion (Tmax of 2 hr at 3.75 g/sq m) whereas, benzoate concentrations declined rapidly (Tmax of 1.5 hr at 3.75 g/sq m) and were undetectable at 14 and 26 hours following the 3.75 and 4 g/sq m dose, respectively.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

苯乙酰谷氨酰胺通过肾小球过滤和肾小管分泌由肾脏排出。

... Phenylacetylglutamine is excreted by the kidneys via glomerular filtration and tubular secretion. ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

尚未知晓苯乙酸钠或苯甲酸钠或其结合代谢物是否会分布到乳汁中。

/It is/ not known whether sodium phenylacetate or sodium benzoate or their conjugated metabolites are distributed into milk.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 安全说明：
  S24/25
• WGK Germany：
  3
• 海关编码：
  2916340090
• 储存条件：
  库房应保持通风、低温和干燥，并与氧化剂分开存放。

制备方法与用途

化学性质：

• 白色粉块状固体。

用途：

• 主要用于制药工业，主要用于制造青霉素。

类别：有毒物质

毒性分级：低毒

急性毒性：

• 腹腔注射 - 小鼠 LD50: 2710 毫克/公斤
• 静脉注射 - 小鼠 LD50: 1500 毫克/公斤

可燃性危险特性：

• 遇明火、高热可燃；燃烧时产生氧化钠刺激烟雾。

储运特性：

• 库房应通风低温干燥存放；
• 与氧化剂分开存放。

灭火剂：

• 可使用砂土、泡沫、二氧化碳或雾状水进行灭火。

反应信息

• 作为反应物：
  描述：

  sodium phenylacetate 在 palladium dichloride 、 1-(125I)iodanylpyrrolidine-2,5-dione 、 三氟乙酸 作用下， 以 氘代乙腈 为溶剂， 反应 24.25h， 生成
  参考文献：
  名称：

  Palladium-Mediated Site-Selective C–H Radio-iodination

  摘要：

  The palladium-mediated C-H radio-iodination of arenes using sodium iodide as the primary isotopic source is reported and performed without chemical know-how in 30 min and applied to the synthesis of complex radio-iodinated compounds of biological interest.

  DOI：

  10.1021/acs.orglett.8b02819
• 作为产物：
  描述：

  2-苯乙酰胺 在 盐酸 、 水 、 sodium hydroxide 作用下， 以99.5%的产率得到sodium phenylacetate
  参考文献：
  名称：

  苯乙酸钠晶型A及其制备方法和用途

  摘要：

  本发明提供了苯乙酸钠晶型A，所述晶型的X射线粉末衍射中，2θ衍射角在5.4±0.2°、5.7±0.2°、20.1±0.2°、21.7±0.2°处有特征峰。本发明还提供了苯乙酸钠晶型A的制备方法和用途。实验结果证明，本发明的苯乙酸钠晶型A的化学纯度高、稳定性好。且与现有技术制备的苯乙酸钠晶型化合物的溶液相比，本发明晶型制备的苯乙酸钠溶液稳定性也更好。并且本发明的制备方法简单易操作，反应条件温和，收率大于99.0％，适合工业化生产。

  公开号：

  CN109956862A
• 作为试剂：
  描述：

  乙酸酐 、 邻硝基苯甲醛 在 sodium phenylacetate 作用下， 生成 O-硝基苯亚甲基二乙酸 、 (Z)-3-(2-nitrophenyl)-2-phenylprop-2-enoic acid
  参考文献：
  名称：

  Bakunin; Parlati, Gazzetta Chimica Italiana, 1906, vol. 36 II, p. 264

  摘要：

  DOI：

文献信息

• [EN] COMPOUNDS AND COMPOSITIONS COMPRISING CDK INHIBITORS AND METHODS FOR THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS ET COMPOSITIONS COMPRENANT DES INHIBITEURS DES CDK ET MÉTHODES DE TRAITEMENT DU CANCER
  申请人：UNIV GEORGIA STATE RES FOUND

  公开号：WO2010129858A1

  公开（公告）日：2010-11-11

  Disclosed herein are compounds suitable for use as antitumor agents, methods for treating cancer wherein the disclosed compounds are used in making a medicament for the treatment of cancer, methods for treating a tumor comprising, administering to a subject a composition comprising one or more of the disclosed cytotoxic agents, and methods for preparing the disclosed antitumor agents.

  本文披露了适用作抗肿瘤药剂的化合物，用于治疗癌症的方法，其中所披露的化合物用于制备治疗癌症的药物，治疗肿瘤的方法包括向受试者施用包含一种或多种所披露的细胞毒性药剂的组合物，以及制备所披露的抗肿瘤药剂的方法。
• [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE TYROSINE KINASE DE BRUTON
  申请人：BIOCAD JOINT STOCK CO

  公开号：WO2018092047A1

  公开（公告）日：2018-05-24

  The present invention relates to a new compound of formula I: or pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: V1 is C or N, V2 is C(R2) or N, whereby if V1 is C then V2 is N, if V1 is C then V2 is C(R2), or if V1 is N then V2 is C(R2); each n, k is independently 0, 1; each R2, R11 is independently H, D, Hal, CN, NR'R", C(O)NR'R", C1-C6 alkoxy; R3 is H, D, hydroxy, C(O)C1-C6 alkyl, C(O)C2-C6 alkenyl, C(O)C2-C6 alkynyl, C1-C6 alkyl; R4 is H, Hal, CN, CONR'R", hydroxy, C1-C6 alkyl, C1-C6 alkoxy; L is CH2, NH, O or chemical bond; R1 is selected from the group of the fragments, comprising: Fragment 1, Fragment 2, Fragment 3 each A1, A2, A3, A4 is independently CH, N, CHal; each A5, A6, A7, A8, A9 is independently C, CH or N; R5 is H, CN, Hal, CONR'R", C1-C6 alkyl, non-substituted or substituted by one or more halogens; each R' and R" is independently selected from the group, comprising H, C1-C6 alkyl, C1-C6 cycloalkyl, aryl; R6 is selected from the group: [formula II] each R7, R8, R9, R10 is independently vinyl, methylacetylenyl; Hal is CI, Br, I, F, which have properties of inhibitor of Bruton's tyrosine kinase (Btk), to pharmaceutical compositions containing such compounds, and their use as pharmaceuticals for treatment of diseases and disorder.

  本发明涉及一种新的化合物，其化学式为I：或其药学上可接受的盐、溶剂化合物或立体异构体，其中：V1为C或N，V2为C(R2)或N，如果V1为C，则V2为N，如果V1为C，则V2为C(R2)，或者如果V1为N，则V2为C(R2)；每个n，k独立地为0或1；每个R2，R11独立地为H，D，Hal，CN，NR'R"，C(O)NR'R"，C1-C6烷氧基；R3为H，D，羟基，C(O)C1-C6烷基，C(O)C2-C6烯基，C(O)C2-C6炔基，C1-C6烷基；R4为H，Hal，CN，CONR'R"，羟基，C1-C6烷基，C1-C6烷氧基；L为CH2，NH，O或化学键；R1从包括的片段组中选择：片段1，片段2，片段3，每个A1，A2，A3，A4独立地为CH，N，CHal；每个A5，A6，A7，A8，A9独立地为C，CH或N；R5为H，CN，Hal，CONR'R"，C1-C6烷基，未取代或被一个或多个卤素取代；每个R'和R"独立地从包括H，C1-C6烷基，C1-C6环烷基，芳基的组中选择；R6从组中选择：[化学式II]每个R7，R8，R9，R10独立地为乙烯基，甲基乙炔基；Hal为CI，Br，I，F，具有布鲁顿酪氨酸激酶（Btk）抑制剂的性质，以及含有这种化合物的药物组合物，以及它们作为治疗疾病和紊乱的药物的用途。
• [EN] BRUTON'S TYROSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE DE BRUTON
  申请人：PFIZER

  公开号：WO2014068527A1

  公开（公告）日：2014-05-08

  Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions. (Formula I)

  本文披露了一种与Bruton's酪氨酸激酶（BTK）形成共价键的化合物。公开了制备这些化合物的方法。还披露了包括这些化合物的药物组合物。公开了使用BTK抑制剂的方法，单独或与其他治疗剂联合治疗自身免疫疾病或症状、异源免疫疾病或症状、癌症，包括淋巴瘤，以及炎症性疾病或症状的方法。 (化学式I)
• [EN] TRICYCLIC TRIAZOLE COMPOUNDS THAT MODULATE HSP90 ACTIVITY<br/>[FR] COMPOSÉS TRIAZOLES TRICYCLIQUES MODULANT L'ACTIVITÉ HSP90
  申请人：SYNTA PHARMACEUTICALS CORP

  公开号：WO2009139916A1

  公开（公告）日：2009-11-19

  The present invention relates to substituted tricyclic triazole compounds and compositions comprising substituted tricyclic triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a compound of the invention, or a composition comprising such a compound.

  本发明涉及替代三环三唑化合物和包含替代三环三唑化合物的组合物。该发明还涉及在需要的受体中抑制Hsp90活性的方法，以及预防或治疗高增殖性疾病（如癌症）的方法，其中包括向受体施用本发明的化合物或包含这种化合物的组合物。
• Amino-substituted heterocycles, compositions thereof, and methods of treatment therewith
  申请人：D'Sidocky Neil R.

  公开号：US20080242694A1

  公开（公告）日：2008-10-02

  Provided herein are Heterocyclic Compounds having the following structure: wherein R 1 , R 2 , X, Y and Z are as defined herein, compositions comprising an effective amount of a Heterocyclic Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, metabolic conditions and conditions treatable or preventable by inhibition of a kinase pathway comprising administering an effective amount of a Heterocyclic Compound to a patient in need thereof.

  本文提供具有以下结构的杂环化合物： 其中R1、R2、X、Y和Z如本文所定义，包含有效量杂环化合物的组合物，以及治疗或预防癌症、炎症性疾病、免疫疾病、代谢性疾病以及通过给予患者需要的有效量杂环化合物来抑制激酶途径治疗或预防的疾病的方法。