107007-99-8

• 常用中文名：盐酸格拉司琼
• 常用英文名：Granisetron hydrochloride
• CAS号：107007-99-8
• 分子式：C₁₈H₂₅ClN₄O
• 分子量：348.870
• 相关类别： 原料药 消化系统用药 止吐催吐药
• 发布时间：2018-04-13 08:00:00
• 更新时间：2024-01-02 19:26:11
• Granisetron(BRL 43694A)盐酸盐是5-HT3受体拮抗剂,可作为化疗后止吐剂。

名称

• 中文名: 盐酸格拉司琼
• 英文名: Granisetron hydrochloride
• 中文别名: 1-甲基-N-[内向-9-甲基-9-氮杂双环(3,3,1)壬烷-3-基]-lH-吲唑-3-甲酰胺盐酸盐; N-(内-9-甲基-9-氮杂二环[3,3,1]壬-3-基)-吲哚-3-羧酰胺盐酸盐; 1-甲基-N-[内向-9-甲基-9-氮杂双环[3.3.1]壬烷-3-基]-1H-吲唑-3-甲酰胺盐酸盐; 格拉司琼盐酸盐; 桥-N-(9-甲基-9-氯杂二环[3.3.1]壬-3-基)-1-甲基-1H-吲唑-3-羧酰胺盐酸盐; 1-甲基-N-[(3-endo)-9-甲基-9-氮杂双环[3.3.1]壬-3-基]-1H-吲哚-3-甲酰胺盐酸盐
• 英文别名: Granisetron hydrochloride; 1-méthyl-N-[(3-endo)-9-méthyl-9-azabicyclo[3.3.1]non-3-yl]-1H-indazole-3-carboxamide chlorhydrate; 1H-Indazole-3-carboxamide, 1-methyl-N-[(3-endo)-9-methyl-9-azabicyclo[3.3.1]non-3-yl]-, hydrochloride (1:1); 1-Methyl-N-[(3-endo)-9-methyl-9-azabicyclo[3.3.1]non-3-yl]-1H-indazole-3-carboxamide hydrochloride (1:1); 1H-indazole-3-carboxamide, 1-methyl-N-[(3-endo)-9-methyl-9-azabicyclo[3.3.1]non-3-yl]-, monohydrochloride; MFCD01747034; Granisetron HCl; 1-Methyl-N-[(3-endo)-9-methyl-9-azabicyclo[3.3.1]non-3-yl]-1H-indazole-3-carboxamide hydrochloride; 1-Methyl-N-[(3-endo)-9-methyl-9-azabicyclo[3.3.1]non-3-yl]-1H-indazole-3-carboxamide; 1-methyl-N-[(1S,5R)-9-methyl-9-azabicyclo[3.3.1]nonan-3-yl]indazole-3-carboxamide,hydrochloride; 1-Methyl-N-[(3-endo)-9-methyl-9-azabicyclo[3.3.1]non-3-yl]-1H-indazol-3-carboxamidhydrochlorid; Granisetron (Hydrochloride)

物化性质

• 密度: 1.33g/cm3
• 沸点: 532ºC at 760mmHg
• 熔点: 290-292°C
• 分子式: C₁₈H₂₅ClN₄O
• 分子量: 348.870
• 闪点: 275.6ºC
• 精确质量: 348.171692
• PSA: 50.16000
• LogP: 3.44920
• 外观性状: 白色至灰白色结晶固体
• 蒸汽压: 0mmHg at 25°C
• 折射率: 1.69
• 储存条件: Room temp
• 更多:

  1.性状：白色或微黄白色结晶性粉末，无臭。

  2.熔点（℃）：290-292。

  3.溶解度：易溶于水，较难溶于甲醇，极难溶于乙醇，几不溶于乙醚。

生物活性

• 描述: Granisetron(BRL 43694A)盐酸盐是5-HT3受体拮抗剂,可作为化疗后止吐剂。
• 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]. Sanger GJ, Nelson DR. Selective and functional 5-hydroxytryptamine3 receptor antagonism by BRL 43694 (granisetron). Eur J Pharmacol. 1989 Jan 10;159(2):113-24.

  [2]. Maleki-Dizaji N, Eteraf-Oskouei T, Fakhrjou A, The effects of 5HT3 receptor antagonist granisetron on inflammatory parameters and angiogenesis in the air-pouch model of inflammation. Int Immunopharmacol. 2010 Sep;10(9):1010-6.

  [3]. Boccia RV, Gordan LN, Clark G, Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy: a randomized, double-blind, phase III

MSDS

Granisetron Hydrochloride Revision number: 5 SAFETY DATA SHEET Section1. IDENTIFICATION Product name:Granisetron Hydrochloride Revision number:5 Section2. HAZARDS IDENTIFICATION GHS classification PHYSICAL HAZARDSNot classified HEALTH HAZARDS Acute toxicity (Oral)Category 4 Not classified ENVIRONMENTAL HAZARDS GHS label elements, including precautionary statements Pictograms or hazard symbols Signal wordWarning Hazard statementsHarmful if swallowed Precautionary statements: [Prevention]Do not eat, drink or smoke when using this product. Wash hands thoroughly after handling. IF SWALLOWED: Call a POISON CENTER or doctor/physician if you feel unwell. [Response] Rinse mouth. Dispose of contents/container through a waste management company authorized by [Disposal] the local government. Section3. COMPOSITION/INFORMATION ON INGREDIENTS Substance/mixture:Substance Components:Granisetron Hydrochloride Percent:>98.0%(LC)(T) CAS Number:107007-99-8 Synonyms:1-Methyl-N-[(3-endo)-9-methyl-9-azabicyclo[3.3.1]non-3-yl]-1H-indazole-3- carboxamide Hydrochloride Chemical Formula:C18H24N4O·HCl Section4. FIRST AID MEASURES Inhalation:Remove victim to fresh air and keep at rest in a position comfortable for breathing. Get medical advice/attention if you feel unwell. Skin contact:Remove/Take off immediately all contaminated clothing. Rinse skin with water/shower. If skin irritation or rash occurs: Get medical advice/attention. Granisetron Hydrochloride Section4. FIRST AID MEASURES Eye contact:Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. If eye irritation persists: Get medical advice/attention. Ingestion:Call a POISON CENTER or doctor/physician if you feel unwell. Rinse mouth. Protection of first-aiders:A rescuer should wear personal protective equipment, such as rubber gloves and air- tight goggles. Section5. FIRE-FIGHTING MEASURES Dry chemical, foam, water spray, carbon dioxide. Suitable extinguishing media: Precautions for firefighters: Fire-extinguishing work is done from the windward and the suitable fire-extinguishing method according to the surrounding situation is used. Uninvolved persons should evacuate to a safe place. In case of fire in the surroundings: Remove movable containers if safe to do so. Special protectiveWhen extinguishing fire, be sure to wear personal protective equipment. equipment for firefighters: Section6. ACCIDENTAL RELEASE MEASURES Personal precautions,Use personal protective equipment. Keep people away from and upwind of spill/leak. protective equipment and Entry to non-involved personnel should be controlled around the leakage area by emergency procedures: roping off, etc. Environmental precautions: Prevent product from entering drains. Methods and materials for Sweep dust to collect it into an airtight container, taking care not to disperse it. containment and cleaning Adhered or collected material should be promptly disposed of, in accordance with up: appropriate laws and regulations. Section7. HANDLING AND STORAGE Precautions for safe handling Technical measures:Handling is performed in a well ventilated place. Wear suitable protective equipment. Prevent dispersion of dust. Wash hands and face thoroughly after handling. Use a local exhaust if dust or aerosol will be generated. Advice on safe handling: Avoid contact with skin, eyes and clothing. Conditions for safe storage, including any incompatibilities Storage conditions:Keep container tightly closed. Store in a cool and dark place. Store away from incompatible materials such as oxidizing agents. Packaging material:Comply with laws. Section8. EXPOSURE CONTROLS / PERSONAL PROTECTION Engineering controls:Install a closed system or local exhaust as possible so that workers should not be exposed directly. Also install safety shower and eye bath. Personal protective equipment Respiratory protection: Dust respirator. Follow local and national regulations. Hand protection:Protective gloves. Eye protection:Safety glasses. A face-shield, if the situation requires. Skin and body protection: Protective clothing. Protective boots, if the situation requires. Section9. PHYSICAL AND CHEMICAL PROPERTIES Solid Physical state (20°C): Form:Crystal- Powder Colour:White - Almost white No data available Odour: pH: No data available Melting point/freezing point:292°C (dec.) Boiling point/range:No data available No data available Flash point: Granisetron Hydrochloride Section9. PHYSICAL AND CHEMICAL PROPERTIES Flammability or explosive limits: Lower:No data available Upper:No data available Relative density:No data available Solubility(ies): [Water]No data available No data available [Other solvents] Section10. STABILITY AND REACTIVITY Chemical stability:Stable under proper conditions. Possibility of hazardous No special reactivity has been reported. reactions: Incompatible materials: Oxidizing agents Hazardous decomposition Carbon monoxide, Carbon dioxide, Nitrogen oxides (NOx), Hydrogen chloride products: Section11. TOXICOLOGICAL INFORMATION orl-rat LD50:350 mg/kg Acute Toxicity: ivn-rat LD50:14 mg/kg Skin corrosion/irritation: No data available Serious eyeNo data available damage/irritation: Germ cell mutagenicity: mmo-sat 5 gm/L (+S9) cyt-hmn-lym 1500 mg/L Carcinogenicity: No data available IARC = NTP =No data available No data available Reproductive toxicity: RTECS Number:NK7882200 Section12. ECOLOGICAL INFORMATION Ecotoxicity: Fish:No data available Crustacea:No data available Algae:No data available Persistence / degradability: No data available No data available Bioaccumulative potential(BCF): Mobility in soil Log Pow:No data available Soil adsorption (Koc):No data available Henry's LawNo data available constant(PaM3/mol): Section13. DISPOSAL CONSIDERATIONS Recycle to process, if possible. Consult your local regional authorities. You may be able to dissolve or mix material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber system. Observe all federal, state and local regulations when disposing of the substance. Section14. TRANSPORT INFORMATION Hazards Class:Does not correspond to the classification standard of the United Nations UN-No:Not listed Granisetron Hydrochloride Section15. REGULATORY INFORMATION Safe management ordinance of dangerous chemical product (State Council announces on January 26, 2002 and revised on February 16,2011): Safe use and production, the storage of a dangerous chemical, transport, loading and unloading were prescribed. SECTION 16 - ADDITIONAL INFORMATION N/A

毒性和生态

毒理学数据: 急性毒性LD50、雌小鼠，雄、雌大鼠(mg/kg)：17，25，14，16静脉注射。 CHEMICAL IDENTIFICATION RTECS NUMBER : NK7882200 CHEMICAL NAME : 1H-Indazole-3-carboxamide, 1-methyl-N-(9-methyl-9-azabicyclo(3.3.1)non-3-yl)-, monohydrochloride, endo- CAS REGISTRY NUMBER : 107007-99-8 LAST UPDATED : 199612 DATA ITEMS CITED : 12 MOLECULAR FORMULA : C18-H24-N4-O.Cl-H MOLECULAR WEIGHT : 348.92 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 350 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 14 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Behavioral - muscle contraction or spasticity TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 350 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 17 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory stimulation TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 3 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - tremor Gastrointestinal - nausea or vomiting TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 4500 mg/kg/30D-I TOXIC EFFECTS : Liver - changes in liver weight Blood - changes in leukocyte (WBC) count Related to Chronic Data - death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 18200 mg/kg/26W-I TOXIC EFFECTS : Liver - changes in liver weight Blood - changes in platelet count Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 325 mg/kg/30D-I TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous DOSE : 52 mg/kg SEX/DURATION : male 10 week(s) pre-mating female 2 week(s) pre-mating - 19 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) MUTATION DATA TYPE OF TEST : Cytogenetic analysis TEST SYSTEM : Human Lymphocyte DOSE/DURATION : 1500 mg/L REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 24,6795,1990

安全

• 符号: GHS07
• 信号词: Warning
• 危害声明: H302
• 警示性声明: P301 + P312 + P330
• 个人防护装备: dust mask type N95 (US);Eyeshields;Faceshields;Gloves
• 危害码 (欧洲): Xn: Harmful;Xi: Irritant;
• 风险声明 (欧洲): R22
• 安全声明 (欧洲): 26-36-37
• 危险品运输编码: NONH for all modes of transport
• RTECS号: NK7882200
• 海关编码: 2933990090

合成路线

76272-41-8 106649-02-9 ~% 107007-99-8

文献：US4886808 A1, ;

109889-09-0 ~74% 107007-99-8

文献：INKE, S.A. Patent: WO2008/151677 A1, 2008 ; Location in patent: Page/Page column 13 ;

上下游产品

上游产品  3
109889-09-0 76272-41-8 106649-02-9
下游产品  1
109889-09-0

制备

化合物(I)和化合物(Ⅱ)反应，即得格拉司琼。用氯化氢-乙醇酸化，得到盐酸格拉司琼。

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%