99614-02-5

• 常用中文名：昂丹司琼
• 常用英文名：Ondansetron
• CAS号：99614-02-5
• 分子式：C₁₈H₁₉N₃O
• 分子量：293.363
• 相关类别： 原料药 消化系统用药 止吐催吐药
• 发布时间：2018-07-10 18:52:42
• 更新时间：2024-01-02 10:21:44
• Ondansetron(GR38032)是5- HT3受体拮抗剂。
• 本品为一种高度选择性的5-羟色胺3（5-HT3）受体拮抗剂，能抑制由化疗和放疗引起的恶心呕吐，其作用机制尚不完全清楚。一般认为，化疗和放疗可引起小肠的嗜铬细胞释放5-HT3，并通过5-HT3受体引起迷走传入神经兴奋从而导致呕吐反射，而昂丹司琼可阻断这一反射发生。 昂丹司琼本品不影响行为效率，无镇静作用，且不改变血浆催乳素水平。口服吸收迅速，单剂量8mg，tmax为1.5小时，Cmax为30ng/ml，口服生物利用度约为60%；Vd约为140L，t1/2β约3小时；血浆蛋白结合率为70%～76%。主要自肝脏代谢，代谢产物主要自粪和尿排泄，50%以内的本品以原形自尿排出。老年人由于代谢减慢，服用本品后消除半衰期延长（5小时），同时口服生物利用度提高（65%）；严重肝功能障碍患者系统清除率可显著减少，消除半衰期可延长至15～32小时，同时口服生物利用度可接近100%。
  本品是强效、高选择性的5—HT3受体拮抗剂，有强镇吐作用。化疗药物和放射治疗可造成小肠释放5—HT，经由5—HT3受体激活迷走神经的传入支，触发呕吐反射。本品能阻断这一反射的触发。迷走神经传入支的激动也可引起位于第四脑室底部Postrema区的5—HT释放，从而经过中枢机制而加强。本品对化疗、放疗引起的恶心、呕吐,系通过拮抗位于周围和中枢神经局部的神经原的5—HT受体而发挥止吐作用。手术后恶心、呕吐的作用机制未明，但可能类似细胞毒类致恶心、呕吐的共同途径而诱发。本品尚能抑制因阿片诱导的恶心，其作用机理尚不清楚。由于本品的高选择性作用，因而不具有其他止吐药的副作用，如锥体外系反应、过度镇静等。

名称

• 中文名: 昂旦司琼
• 英文名: 9-Methyl-3-((2-methyl-1H-imidazol-1-yl)methyl)-2,3-dihydro-1H-carbazol-4(9H)-one
• 中文别名: 昂丹司琼; 1,2,3,9-四氢-9-甲基-3-[(2-甲基-1H-咪唑-1-基)甲基]-4H-咔唑-4-酮; 恩丹西酮
• 英文别名: ONDANSETRON HYDROCHLORIDE DIHYDRATE; 9-Methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-1,2,3,9-tetrahydro-4H-carbazol-4-one; GR 38032F; 4H-Carbazol-4-one, 1,2,3,9-tetrahydro-9-methyl-3-((2-methyl-1H-imidazol-1-yl)methyl)-; 9-METHYL-3-[(2-METHYL-1H-IMIDAZOLYL)METHYL]-1,2,3,9-TETRAHYDRO-4H-CARBAZOLE-4-ONE; 1,2,3,9-Tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one; ONDANSETRON-D5; ONDANSETRON HCL D6; 9-METHYL-3-(2-METHYL-1H-IMIDAZOLYL)-METHYL-1,2,3,9-TETRAHYDRO-4H-CARBAZOLE-4-ONE; Zofran; ONDANSETRONBASE; R(+)-Ondansetron; Ondansetro; ONDANSETRON HYDROCHLORIDE; 9-METHYL-3-[(2-METHYL-1H-IMIDAZOLYL)-METHYL]-1,2,3,9-TETRAHYDRO-4H-CARBAZOLE-4-ONE; GR 38032X; ONDANESTRON; GR-38032F; MFCD00764297; 4H-Carbazol-4-one, 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-; ONDANSETRON FOR LC SYSTEM SUITABILITY, EP STANDARD; Ondansetron; ONDANSETRON HCL; EINECS 619-449-4

物化性质

• 密度: 1.3±0.1 g/cm3
• 沸点: 546.0±30.0 °C at 760 mmHg
• 熔点: 231 - 232ºC
• 分子式: C₁₈H₁₉N₃O
• 分子量: 293.363
• 闪点: 284.0±24.6 °C
• 精确质量: 293.152802
• PSA: 39.82000
• LogP: 2.07
• 外观性状: 白色至黄色晶体
• 蒸汽压: 0.0±1.5 mmHg at 25°C
• 折射率: 1.678
• 储存条件: −20°C
• 水溶解性: H2O: >5 mg/mL
• 分子结构:

  1、 摩尔折射率：86.75

  2、 摩尔体积（cm³/mol）：230.1

  3、 等张比容（90.2K）：608.7

  4、 表面张力（dyne/cm）：48.9

  5、 极化率（10-24cm3）：34.39

• 更多:

  1.熔点（ºC）：从甲醇结晶，熔点231-232℃

生物活性

• 描述: Ondansetron(GR38032)是5- HT3受体拮抗剂。
• 相关类别:
  信号通路 >> G 蛋白偶联受体/G 蛋白 >> 5-HT受体
  信号通路 >> 神经信号通路 >> 5-HT受体
  研究领域 >> 神经疾病
• 参考文献:

  [1]. Brown AM, et al. Ion permeation and conduction in a human recombinant 5-HT3 receptor subunit (h5-HT3A). J Physiol. 1998 Mar 15;507 ( Pt 3):653-65.

  [2]. Barann M, et al. Recombinant human 5-HT3A receptors in outside-out patches of HEK 293 cells: basic properties and barbiturate effects. Naunyn Schmiedebergs Arch Pharmacol. 2000 Sep;362(3):255-65.

  [3]. Wildeboer KM, et al. Ondansetron results in improved auditory gating in DBA/2 mice through a cholinergic mechanism. Brain Res. 2009 Dec 1;1300:41-50.

  [4]. Khedhaier A, et al. Circadian rhythms in toxic effects of the serotonin antagonist ondansetron in mice. Chronobiol Int. 2003 Nov;20(6):1103-16.

  [5]. Umathe SN, et al. The 5-HT3 receptor antagonist, ondansetron, blocks the development and expression of ethanol-induced locomotor sensitization in mice. Behav Pharmacol. 2009 Feb;20(1):78-83.

  [6]. Doggrell SA, et al. Cardiac safety concerns for ondansetron, an antiemetic commonly used for nausea linked to cancer treatment and following anaesthesia. Expert Opin Drug Saf. 2013 May;12(3):421-31.

MSDS

Material Safety Data Sheet Section1. Identification of the substance Product Name: Ondansetron Synonyms: Section2. Hazards identification Harmful by inhalation, in contact with skin, and if swallowed. Section3. Composition/information on ingredients. Ingredient name:Ondansetron CAS number:99614-02-5 Section4. 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. Section5. 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. Section6. 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. Section7. 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: Section8. 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. Section9. Physical and chemical properties Appearance:Not specified Boiling point:No data No data Melting point: Flash point:No data Density:No data Molecular formula:C18H19N3O Molecular weight:293.4 Section10. Stability and reactivity Conditions to avoid: Heat, flames and sparks. Materials to avoid: Oxidizing agents. Possible hazardous combustion products: Carbon monoxide, nitrogen oxides. Section11. Toxicological information No data. Section12. Ecological information No data. Section13. 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. Section14. Transportation information Non-harzardous for air and ground transportation. Section15. 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

安全

• 危害码 (欧洲): T: Toxic;Xi: Irritant;
• 风险声明 (欧洲): R25
• 安全声明 (欧洲): S45
• 危险品运输编码: UN 2811 6.1/PG 3
• WGK德国: 3
• RTECS号: FE6375500
• 海关编码: 2933990090

合成路线

上下游产品

上游产品  9
99614-01-4 60498-72-8 99614-64-9 27387-31-1
51-80-9 1630-73-5 20073-50-1 51200-87-4
880-09-1
下游产品  1
99614-01-4

制备

2-溴苯胺和1,3-环己二酮反应，再脱溴化氢环合，生成四氢咔唑衍生物，该衍生物和二甲胺及二聚甲醛反应，接着和碘甲烷反应，最后和2-甲基-1H-咪唑在二甲基甲酰胺中搅拌反应，得到昂丹司琼。

或者由环己酮和苯肼反应，得四氢咔唑。将其溶于四氢呋喃和水中，在氮气中滴加2,3,5,6-四氯-1,4-苯醌的四氢呋喃溶液，搅拌得氧化产物。该产物与乙醇、浓盐酸、多聚甲醛和盐酸二甲胺，一起回流。处理后再在丙酮中加浓盐酸搅拌，得到的氨甲基化产物再和2-甲基咪唑反应；接着和碘甲烷及碳酸钾，在室温搅拌至固体消失。经处理得到昂丹司琼。将其溶于丙酮和水的混合液中，加入浓盐酸反应，可得盐酸昂丹司琼二水合物。

也可以由1,2,3,9-四氧-4H-咔唑-4-酮与二甲胺及二聚甲醛反应，再和碘甲烷反应，最后和2-甲基-1H-咪唑在二甲基甲酰胺中反应，得到昂丹司琼。

海关

海关编码	2933990090
中文概述	2933990090. 其他仅含氮杂原子的杂环化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:20.0%
申报要素	品名, 成分含量, 用途, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期
Summary	2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%