盐酸帕洛诺司琼 | 135729-62-3

• 物质功能分类: 生物化工 - 抑制剂 - 神经信号通路(Neuronal Signaling)
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 中文名称: 盐酸帕洛诺司琼
• 中文别名: 帕洛诺司琼盐酸盐；帕洛诺司琼；(3aS)-2-[(3s)-1-氮杂双环[2.2.2]辛烷基-2,3,3a,4,5,6-六氢-1-氧代-1H-苯并[de]异喹啉盐酸盐；盐酸帕洛司琼
• 英文名称: palonosetron hydrochloride
• 英文别名: aloxi；2-[(S)-1-azoniabicyclo[2.2.2]oct-3-yl]-2,3,3a,4,5,6-hexahydro-1H-benz[de]isoquinolin-1-one chloride；(3aS)-2-[(3S)-1-azoniabicyclo[2.2.2]octan-3-yl]-3a,4,5,6-tetrahydro-3H-benzo[de]isoquinolin-1-one;chloride
• CAS: 135729-62-3
• 化学式: C₁₉H₂₄N₂O*ClH
• mdl: MFCD00939524
• 分子量: 332.873
• InChiKey: OLDRWYVIKMSFFB-SSPJITILSA-N

物化性质

• 熔点：
  >290°C
• 比旋光度：
  D25 -94.1° (c = 0.4 in water)
• 溶解度：
  可溶于甲醇（轻微加热）、水（轻微）

计算性质

• 辛醇/水分配系数(LogP)：
  2.55
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.631
• 拓扑面积：
  23.6
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090
• 危险品运输编号：
  NONH for all modes of transport
• WGK Germany：
  3
• 危险标志：
  GHS07
• 危险性描述：
  H302
• 危险性防范说明：
  P301 + P312 + P330
• 储存条件：
  Refrigerator

SDS

Palonosetron Hydrochloride Revision number: 5.3
SAFETY DATA SHEET

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Section 1. IDENTIFICATION
Product name: Palonosetron Hydrochloride

Revision number: 5.3

---

Section 2. HAZARDS IDENTIFICATION
GHS classification
PHYSICAL HAZARDS Not classified
Not classified
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS Not classified
GHS label elements, including precautionary statements
Pictograms or hazard symbols None
No signal word
Signal word
Hazard statements None
None
Precautionary statements:

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substance/mixture: Substance
Components: Palonosetron Hydrochloride
Percent: >98.0%(HPLC)(T)
CAS Number: 135729-62-3
Chemical Formula: C19H24N2O·HCl

---

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.
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: Get medical advice/attention if you feel unwell. Rinse mouth.
A rescuer should wear personal protective equipment, such as rubber gloves and air-
Protection of first-aiders:
tight goggles.

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Section 5. FIRE-FIGHTING MEASURES
Suitable extinguishing Dry chemical, foam, water spray, carbon dioxide.
media:
Specific hazards arising Take care as it may decompose upon combustion or in high temperatures to
from the chemical: generate poisonous fume.
Palonosetron Hydrochloride

---

Section 5. FIRE-FIGHTING MEASURES
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
Use personal protective equipment. Keep people away from and upwind of spill/leak.
Personal precautions,
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
Handling is performed in a well ventilated place. Wear suitable protective equipment.
Technical measures:
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 refrigerator.
Store away from incompatible materials such as oxidizing agents.
Heat-sensitive
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: Very pale yellow - Pale reddish yellow
No data available
Odour:
pH: No data available
Melting point/freezing point:307°C (dec.)
Boiling point/range: No data available
No data available
Flash point:
Flammability or explosive
limits:
Lower: No data available
No data available
Upper:
Relative density: No data available
Solubility(ies):
[Water] Very soluble
[Other solvents]
Soluble: Propylene glycol
Palonosetron Hydrochloride

---

Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Slightly soluble: Dimethyl sulfoxide(DMSO)
Very slightly Ethanol, Isopropanol
soluble:

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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
Acute Toxicity: No data available
Skin corrosion/irritation: No data available
Serious eye No data available
damage/irritation:
Germ cell mutagenicity: No data available
Carcinogenicity:
IARC = No data available
No data available
NTP =
Reproductive toxicity: No data available

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Section 12. ECOLOGICAL INFORMATION
Ecotoxicity:
Fish: No data available
Crustacea: No data available
No data available
Algae:
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):

---

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

---

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.
Palonosetron Hydrochloride

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

用途

盐酸帕洛诺司琼是5-羟色胺5-HT3受体拮抗剂，用于预防和治疗化学疗法诱发的恶心和呕吐（CINV），是一种止吐药。

恶心呕吐药

盐酸帕洛诺司琼是一种抑制恶心呕吐的新型高选择性、高亲和性5-HT3受体拮抗剂。它通过阻断呕吐反射中枢外周神经元的突触前5-HT受体，以及直接影响中枢神经系统内5-HT受体兴奋产生的冲动，进而减少恶心和呕吐的发生率。临床上主要用于治疗由中、重度致吐性化疗药物引起的急性、延迟性恶心和呕吐。因其疗效高、毒副作用小、半衰期长（约40小时）、用药剂量小等特点而备受关注。

盐酸帕洛诺司琼以1,2,3,4-四氢-1-萘甲酸为起始原料，经拆分、胺化、还原、关环、成盐制得。临床研究表明，它能安全地与皮质类固醇类、镇痛药、止吐药、解痉药和抗胆碱能药物一起应用；且鼠肿瘤模型研究表明，不会抑制所研究的五种化疗药物（顺铂、环磷酰胺、阿糖胞苷、阿霉素和丝裂霉素C）的抗癌活性。

生物活性

盐酸帕洛诺司琼(Palonosetron HCl, RS 25259)是一种高效高选择性的第二代5-HT3受体拮抗剂，对5-HT3受体的结合亲和性比其他同类药物高100倍（Palonosetron pK _i 10.5，而granisetron pK _i 8.91, tropisetron pK _i 8.81, ondansetron pK _i 8.39, dolasetron pK _i 7.6）。其血浆半衰期约为40小时，远超同种类拮抗剂（如ondansetron, 4小时; tropisetron, 7.3 小时; dolasetron, 7.5 小时; ranisetron, 8.9小时）。

靶点

• Target: 5-HT3

体外研究

Palonosetron 是一种高效高选择性的第二代5-HT3 受体拮抗剂，对5-HT3受体的结合亲和性比其他同类药物高100倍（Palonosetron pK _i 10.5，而granisetron pK _i 8.91, tropisetron pK _i 8.81, ondansetron pK _i 8.39, dolasetron pK _i 7.6）。其血浆半衰期约为40小时，远超同种类拮抗剂（如ondansetron, 4小时; tropisetron, 7.3 小时; dolasetron, 7.5 小时; ranisetron, 8.9小时）。

反应信息

• 作为反应物：
  描述：

  盐酸帕洛诺司琼 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 乙腈 为溶剂， 反应 5.0h， 生成 α-bromopalonosetron
  参考文献：
  名称：

  盐酸帕洛诺司琼代谢杂质的制备方法

  摘要：

  本发明属于药物合成技术领域，具体涉及一种盐酸帕洛诺司琼代谢杂质的制备方法。所述盐酸帕洛诺司琼代谢杂质包括α‑羟基帕洛诺司琼、α‑酮帕洛诺司琼和氮氧化α‑酮帕洛诺司琼；所述的制备方法为：以帕洛诺司琼为原料，经取代反应、水解反应制备α‑羟基帕洛诺司琼；以α‑羟基帕洛诺司琼为原料，经氧化反应制备α‑酮帕洛诺司琼；以α‑酮帕洛诺司琼为原料，经氧化反应制备氮氧化α‑酮帕洛诺司琼。本发明制备路线短，原料易得，所得产物纯度高，为盐酸帕洛诺司琼质量研究提供基础，具有很高的商业价值。

  公开号：

  CN111018852A
• 作为产物：
  描述：

  3-奎宁环酮盐酸盐 在 5%-palladium/activated carbon 、 氢气 、 三乙胺 作用下， 以 甲苯 、 正丁醇 为溶剂， 反应 30.0h， 生成 盐酸帕洛诺司琼
  参考文献：
  名称：

  一种盐酸帕洛诺司琼盐酸盐的合成工艺

  摘要：

  本发明公开了一种盐酸帕洛诺司琼盐酸盐的合成工艺，包括如下步骤：步骤S1，以3,4‑二氢‑1‑萘甲胺盐酸盐和3‑奎宁环酮盐酸盐为原料缩合还原制备得到N‑[(3,4‑二氢萘‑1‑基)甲基]‑(S)‑1‑氮杂二环[2.2.2]辛烷‑3‑胺的正丁醇溶液；步骤S2，直接在N‑[(3,4‑二氢萘‑1‑基)甲基]‑(S)‑1‑氮杂二环[2.2.2]辛烷‑3‑胺的正丁醇溶液中加入催化剂氢化还原得到N‑[(1,2,3,4‑四氢萘‑1‑基)甲基]‑(S)‑1‑氮杂二环[2.2.2]辛烷‑3‑胺；步骤S3，将N‑[(1,2,3,4‑四氢萘‑1‑基)甲基]‑(S)‑1‑氮杂二环[2.2.2]辛烷‑3‑胺环合成盐得到盐酸帕洛诺司琼盐酸盐。本发明提供的合成工艺条件温和、步骤简单、收率高，优于现有技术。

  公开号：

  CN107089979B
• 作为试剂：
  描述：

  帕洛诺司琼 、 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 、 在 盐酸帕洛诺司琼 、 乙醇甲醇混合物 作用下， 以 甲醇 、 乙醇 为溶剂， 以yielded 5.0 g of the title product (I) which的产率得到盐酸帕洛诺司琼
  参考文献：
  名称：

  Process for the preparation of substantially pure palonosetron and its acid salts

  摘要：

  本发明涉及一种改进和可扩展的制备基本纯的帕洛诺塞特龙及其酸加成盐（特别是盐酸盐（I））的过程，其包括：（a）通过在适当的有机溶剂中在压力下与适当选择的氢化催化剂进行氢化，将中间体（IIa）本身或其游离基（II）转化为掺杂有不同量未转化的中间体（II）或（IIa）的不对映异构体帕洛诺塞特龙（VIII）或（VIIIa）的粗混合物；（b）通过卤化反应将掺杂有不同量未转化的中间体（II）或（IIa）的不对映异构体帕洛诺塞特龙（VIII）或（VIIIa）的粗混合物基本上从（II）或（IIa）中清除；（c）最后，通过选择性结晶从适当的单一或混合有机溶剂中将基本上不含中间体（II）或（IIa）的不对映异构体帕洛诺塞特龙（VIII）或其盐酸盐（VIIIa）转化为所需的基本纯帕洛诺塞特龙盐酸盐（I）。

  公开号：

  US08093391B2

文献信息

• [EN] SUBSTITUTED TRICYCLIC COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS TRICYCLIQUES SUBSTITUÉS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：BAYER HEALTHCARE AG

  公开号：WO2009033581A1

  公开（公告）日：2009-03-19

  This invention relates to novel compounds and processes for their preparation, methods of treating diseases, particularly cancer, comprising administering said compounds, and methods of making pharmaceutical compositions for the treatment or prevention of disorders, particularly cancer.

  这项发明涉及新颖化合物及其制备方法，治疗疾病的方法，特别是癌症，包括给予这些化合物，以及制备用于治疗或预防疾病，特别是癌症的药物组合物的方法。
• [EN] ESTROGEN RECEPTOR MODULATORS AND USES THEREOF<br/>[FR] MODULATEURS DE RÉCEPTEURS D'OESTROGÈNES ET LEURS UTILISATIONS
  申请人：SERAGON PHARMACEUTICALS INC

  公开号：WO2013142266A1

  公开（公告）日：2013-09-26

  Described herein are compounds that are estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.

  本文描述了一些雌激素受体调节剂化合物。还描述了包括本文描述的化合物在内的药物组合物和药物，以及使用这些雌激素受体调节剂的方法，单独或与其他化合物结合，用于治疗与雌激素受体介导或依赖的疾病或症状。
• [EN] BETA-SUBSTITUTED BETA-AMINO ACIDS AND ANALOGS AS CHEMOTHERAPEUTIC AGENTS AND USES THEREOF<br/>[FR] ACIDES BÊTA-AMINÉS SUBSTITUÉS EN BÊTA ET ANALOGUES À UTILISER EN TANT QU'AGENTS DE CHIMIOTHÉRAPIE ET LEURS UTILISATIONS
  申请人：QUADRIGA BIOSCIENCES INC

  公开号：WO2017024009A1

  公开（公告）日：2017-02-09

  β-Substituted β-amino acids, β-substituted β-amino acid derivatives, and β-substituted β-amino acid analogs and (bio)isosteres and their use as chemotherapeutic agents are disclosed. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and (bio)isosteres are selective LAT1/4F2hc substrates and exhibit rapid uptake and retention in tumors expressing the LAT1/4F2hc transporter. Methods of synthesizing the β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and methods of using the compounds for treating cancer are also disclosed. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs exhibit selective uptake in tumor cells expressing the LAT1/4F2hc transporter and accumulate in cancerous cells when administered to a subject in vivo. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and (bio)isosteres exhibit cytotoxicity toward several tumor types.

  β-取代β-氨基酸，β-取代β-氨基酸衍生物，β-取代β-氨基酸类似物和（生物）同位素以及它们作为化疗药物的用途被披露。β-取代β-氨基酸衍生物和β-取代β-氨基酸类似物和（生物）同位素是选择性LAT1/4F2hc底物，并在表达LAT1/4F2hc转运蛋白的肿瘤中表现出快速摄取和保留。还披露了合成β-取代β-氨基酸衍生物和β-取代β-氨基酸类似物的方法以及使用这些化合物治疗癌症的方法。β-取代β-氨基酸衍生物和β-取代β-氨基酸类似物在表达LAT1/4F2hc转运蛋白的肿瘤细胞中表现出选择性摄取，并在体内给予受试者后在癌细胞中积累。β-取代β-氨基酸衍生物和β-取代β-氨基酸类似物和（生物）同位素对几种肿瘤类型表现出细胞毒性。
• [EN] DISUBSTITUTED 5-FLUORO PYRIMIDINE DERIVATIVES CONTAINING A SULFOXIMINE GROUP<br/>[FR] DÉRIVÉS DE 5-FLUOROPYRIMIDINE DISUBSTITUÉS CONTENANT UN GROUPE SULFOXIMINE
  申请人：BAYER IP GMBH

  公开号：WO2013037894A1

  公开（公告）日：2013-03-21

  The present invention relates to disubstituted 5-fluoro pyrimidine derivatives containing a sulfoximine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).

  本发明涉及含有一种磺氧亚胺基团的二取代5-氟嘧啶衍生物，其一般式（I）如本文所述和定义，并且涉及其制备方法，以及用于治疗和/或预防疾病，特别是高增殖性疾病和/或病毒诱导的传染病和/或心血管疾病的用途。该发明还涉及在制备上述一般式（I）化合物中有用的中间化合物。
• [EN] 4-ARYL-N-PHENYL-1,3,5-TRIAZIN-2-AMINES CONTAINING A SULFOXIMINE GROUP<br/>[FR] 4-ARYL-N-PHÉNYL-1,3,5-TRIAZINE-2-AMINES CONTENANT UN GROUPE SULFOXIMINE
  申请人：BAYER IP GMBH

  公开号：WO2012160034A1

  公开（公告）日：2012-11-29

  The present invention relates to 4-aryl-N-phenyl-1,3,5-triazin-2-amines containing a sulfoximine group of general formula (I) or (Ia) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I) or (Ia).

  本发明涉及一种含有一般式(I)或(Ia)中所述和定义的亚砜基团的4-芳基-N-苯基-1,3,5-三嗪-2-胺，以及它们的制备方法，它们用于治疗和/或预防疾病，特别是高增殖性疾病和/或病毒诱导的传染病和/或心血管疾病。该发明还涉及在制备所述一般式(I)或(Ia)化合物中有用的中间化合物。