Granisetron hydrochloride | 107007-99-8

• 物质功能分类: 原料药 - 消化系统用药 - 止吐催吐药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: Granisetron hydrochloride
• 英文别名: endo-N-(9-methyl-9-azabicyclo<3.3.1>nonan-3-yl)-1-methyl-1H-indazole-3-carboxamide monohydrochloride；1-methyl-N-[(1R,3r,5S)-9-methyl-9-azabicyclo[3.3.1]non-3-yl]-1H-indazole-3-carboxamide hydrochloride；granisetrona hydrochloride；granisetron HCl；granisetron
• CAS: 107007-99-8
• 化学式: C₁₈H₂₄N₄O*ClH
• 分子量: 348.876
• InChiKey: QYZRTBKYBJRGJB-WQTKJZBYSA-N

物化性质

• 熔点：
  290-292°C
• 溶解度：
  H2O：>10mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  2.74
• 重原子数：
  24.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  50.16
• 氢给体数：
  1.0
• 氢受体数：
  4.0

安全信息

• 危险品标志：
  Xn,Xi
• 安全说明：
  S26,S36,S37
• 危险类别码：
  R22
• WGK Germany：
  3
• 海关编码：
  2933990090
• RTECS号：
  NK7882200
• 储存条件：
  室温

SDS

Granisetron Hydrochloride Revision number: 5
SAFETY DATA SHEET

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Section 1. IDENTIFICATION
Product name: Granisetron Hydrochloride

Revision number: 5

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Section 2. HAZARDS IDENTIFICATION
GHS classification
PHYSICAL HAZARDS Not classified
HEALTH HAZARDS
Acute toxicity (Oral) Category 4
Not classified
ENVIRONMENTAL HAZARDS
GHS label elements, including precautionary statements
Pictograms or hazard symbols
Signal word Warning
Hazard statements Harmful 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.

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Section 3. 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

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Section 4. 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

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Section 4. 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.

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Section 5. 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 protective When extinguishing fire, be sure to wear personal protective equipment.
equipment for firefighters:

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Section 6. 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.

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Section 7. 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.

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Section 8. 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.

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Section 9. 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

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Section 9. 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]

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Section 10. 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:

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Section 11. TOXICOLOGICAL INFORMATION
orl-rat LD50:350 mg/kg
Acute Toxicity:
ivn-rat LD50:14 mg/kg
Skin corrosion/irritation: No data available
Serious eye No 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

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Section 12. 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 Law No data available
constant(PaM3/mol):

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Section 13. 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.

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Section 14. TRANSPORT INFORMATION
Hazards Class: Does not correspond to the classification standard of the United Nations
UN-No: Not listed
Granisetron Hydrochloride

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Section 15. 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.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

盐酸格拉司琼概述

盐酸格拉司琼最初由英国 Beecham公司于80年代中期开发，并于1991年由合并后的Smithkline-Beecham (SB)公司在南非首次推出3mg注射剂Kytri1。自此，包括1mg口服片剂和1mg注射剂在内的产品已在美、英、法、日、德、意等全球四十多个国家和地区上市。随后，当SB公司与葛兰素公司合并时，该品转给了罗氏公司。

国外研究资料表明，盐酸格拉司琼具有高度的受体选择性。其与5-HT3受体的亲和力是其他如5-HT1、5-HT2、多巴胺D1、D1、组胺H1、苯二氮卓及阿片受体的4000—10000倍，而恩丹西酮与这些受体的差异仅1000倍。在预防顺铂致雪貂呕吐的试验中，盐酸格拉司琼三个剂量组（2×0.005、2×0.05及2×0.5mg/kg）止吐率分别为93%、96%和100%，而恩丹西酮2×2.5mg/kg的止吐率为89%，这表明盐酸格拉司琼抗呕吐活性强于恩丹西酮至少5倍。毒性研究结果显示，小剂量时该药物能够达到很好的止吐作用且副作用很小，但大剂量时可能会出现心血管系统的异常。由于临床推荐剂量（3mg/d）非常小，仅为动物试验所用的最低剂量（＜1mg/kg）的一半，因此临床应用是安全的。

药代动力学研究表明，盐酸格拉司琼在病人体内的半衰期为9小时，在健康人中则为4小时；老年人的半衰期为7.7小时，青年人则为4.9小时。该药物主要在肝脏代谢，以7-羟基盐酸格拉司琼和其他代谢产物形式通过粪便和尿液排出体外。肝功能受损或肝转移癌患者的血浆清除率减少，肾功能不全时其清除率为正常值的1/4。口服观察到很高的首过效应，绝对生物利用度为65%。

化学性质

盐酸格拉司琼是一种白色或微黄白色的结晶性粉末，无臭，易溶于水，较难溶于甲醇，极难溶于乙醇，几乎不溶于乙醚。熔点范围为290-292℃。急性毒性实验中，雌小鼠、雄大鼠和雌大鼠经静脉注射后的LD50分别为17、25、14和16mg/kg。

用途

盐酸格拉司琼是一种外周及中枢神经系统中的5-羟色胺3(5-HT3)的选择性拮抗剂，用于细胞毒药物或放疗引起的恶心和呕吐。此外，它还可用作解痉药和止吐药，用于化、放疗所致的恶心和呕吐。

生产方法

盐酸格拉司琼由化合物(I)和化合物(Ⅱ)反应获得。通过用氯化氢-乙醇进行酸化处理得到最终产物。

反应信息

• 作为反应物：
  描述：

  Granisetron hydrochloride 在 氨 、 水 作用下， 反应 0.5h， 生成 granisetron
  参考文献：
  名称：

  CRYSTALLINE GRANISETRON BASE AND PRODUCTION PROCESS THEREFOR

  摘要：

  提供的是结晶的格拉尼色隆碱基I形式及其生产工艺，适用于制备格拉尼色隆盐，例如盐酸盐。还提供了一种从结晶的格拉尼色隆碱基I形式制备格拉尼色隆盐的工艺。

  公开号：

  US20080242696A1
• 作为产物：
  描述：

  granisetron 在 盐酸 作用下， 以 水 、 甲苯 为溶剂， 生成 Granisetron hydrochloride
  参考文献：
  名称：

  POLYMORPHIC FORM OF GRANISETRON HYDROCHLORIDE AND METHODS OF MAKING THE SAME

  摘要：

  本发明公开了结晶性盐酸格拉司琼的粉末X射线衍射图谱，其峰位于约14.3、20.4和23.0±0.2度的2θ处，以及制备该物质的方法。

  公开号：

  US20100048613A1

文献信息

• [EN] AMINE-LINKED C3-GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN DEGRADATION<br/>[FR] DÉGRONIMÈRES DE C3-GLUTARIMIDE LIÉS À UNE AMINE POUR LA DÉGRADATION DE PROTÉINES CIBLES
  申请人：C4 THERAPEUTICS INC

  公开号：WO2017197051A1

  公开（公告）日：2017-11-16

  This invention provides amine-linked C3-glutarimide Degronimers and Degrons for therapeutic applications as described further herein, and methods of use and compositions thereof as well as methods for their preparation.

  这项发明提供了胺连接的C3-戊二酰亚胺Degronimers和Degrons，用于治疗应用，如本文进一步描述的，以及它们的使用方法、组合物以及它们的制备方法。
• [EN] AMIDOIMIDAZOPYRIDAZINES AS MKNK-1 KINASE INHIBITORS<br/>[FR] AMIDOIMIDAZOPYRIDAZINES À TITRE D'INHIBITEURS DE KINASES MKNK-1
  申请人：BAYER PHARMA AG

  公开号：WO2014118135A1

  公开（公告）日：2014-08-07

  The present invention relates to amido-substituted imidazopyridazine compounds of general formula (I) : in which A, R1, R2, R3, R4 and n are as defined in the claims, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper- proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients.

  本发明涉及一般式(I)的酰胺取代咪唑吡啶化合物，其中A、R1、R2、R3、R4和n如权利要求中所定义，以及制备所述化合物的方法，用于制备所述化合物的有用中间体化合物，包括所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗或预防疾病的药物组合物，特别是用作唯一药剂或与其他活性成分结合。
• HETEROAROMATIC COMPOUNDS FOR USE AS HIF INHIBITORS
  申请人：Härter Michael

  公开号：US20110301122A1

  公开（公告）日：2011-12-08

  The present application relates to novel substituted aryl compounds, processes for their preparation, their use for treatment and/or prevention of diseases and their use for the preparation of medicaments for treatment and/or prevention of diseases, in particular for treatment and/or prevention of hyperproliferative and angiogenic diseases and those diseases which arise from metabolic adaptation to hypoxic states. Such treatments can be carried out as monotherapy or also in combination with other medicaments or further therapeutic measures.

  本申请涉及新型取代芳基化合物，其制备方法，它们用于治疗和/或预防疾病以及用于制备治疗和/或预防疾病的药物，特别是用于治疗和/或预防过度增殖和血管生成性疾病以及那些由于代谢适应缺氧状态而引起的疾病。这种治疗可以作为单独治疗进行，也可以与其他药物或进一步的治疗措施结合使用。
• [EN] THERAPUETIC USES OF SELECTED PYRIMIDINE COMPOUNDS WITH ANTI-MER TYROSINE KINASE ACTIVITY<br/>[FR] UTILISATIONS THÉRAPEUTIQUES DE COMPOSÉS SÉLECTIONNÉS DE PYRIMIDINE AYANT UNE ACTIVITÉ TYROSINE KINASE ANTIMÈRE
  申请人：UNIV NORTH CAROLINA

  公开号：WO2015157127A1

  公开（公告）日：2015-10-15

  Uses of pyrimidines with anti-Mer tyrosine kinase activity as anti-infective agents, immunostimulatory and immunomodulatory agents, anti-cancer agents (including against MerTK -/- tumors and ITD and TKD mutant forms of Acute Myeloid Leukemia (AML)), and as adjunctive agents in combination with chemotherapeutic, radiation or other standard of care for neoplasms.

  将嘧啶类化合物用作抗Mer酪氨酸激酶活性的抗感染剂、免疫刺激剂和免疫调节剂、抗癌剂（包括对MerTK -/-肿瘤和急性髓样白血病（AML）的ITD和TKD突变形式），以及作为辅助剂与化疗、放疗或其他肿瘤标准治疗联合使用。
• [EN] AMINOIMIDAZOPYRIDAZINES<br/>[FR] AMINOIMIDAZOPYRIDAZINES
  申请人：BAYER PHARMA AG

  公开号：WO2014076162A1

  公开（公告）日：2014-05-22

  The present invention relates to amino-substituted imidazopyridazine compounds of general formula (I), in which A, R1, R2, R3, R4 and n are as defined in the claims, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper- proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients.

  本发明涉及一般式(I)的氨基取代咪唑吡啶化合物，其中A、R1、R2、R3、R4和n如权利要求中所定义，以及制备所述化合物的方法，用于制备所述化合物的有用中间体化合物，包含所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗或预防疾病的药物组合物，特别是用作唯一药剂或与其他活性成分组合使用时，用于治疗或预防过度增殖和/或血管生成障碍的疾病。