132539-06-1

• 常用中文名：奥氮平
• 常用英文名：Olanzapine
• CAS号：132539-06-1
• 分子式：C₁₇H₂₀N₄S
• 分子量：312.432
• 相关类别： 原料药 循环系统用药 抗休克血管活性药
• 发布时间：2018-02-07 08:00:00
• 更新时间：2024-01-02 09:47:47
• Olanzapine(LY170053)是5-HT2和D2受体高亲和性拮抗剂。

名称

• 中文名: 奥氮平
• 英文名: olanzapine
• 中文别名: 奥兰扎平; 2-甲基-4-(4-甲基-1-哌嗪基)-10H-噻吩并[2,3-b][1,5]苯并二氮杂; 2-甲基-4-(4-甲基-1-哌嗪基)-10H-thieno[2,3-b][1,5]苯二氮
• 英文别名: 10H-thieno2,3-b1,5benzodiazepine, 2-methyl-4-(4-methyl-1-piperazinyl)-; Olanzapine; 2-Methyl-4-(4-methyl-1-piperazinyl)- 10H-thieno[2,3-b][1,5]benzodiazepine; 2-Methyl-4-(4-methylpiperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepine; 2-Methyl-4-(4-methylpiperazin-1-yl)-10H-benzo[b]thieno[2,3-e][1,4]diazepine; 2-méthyl-4-(4-méthylpipérazin-1-yl)-10H-thiéno[2,3-b][1,5]benzodiazépine; 2-Methyl-4-(4-methyl-1-piperazinyl)- 10H-thieno[2,3-b][1,5]benzodiazepine LY-170053; Integrol; Oltal; Larmac; ZYPREXA; OLANZAPINE FORM I; 2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine; 2-methyl-4-(4-methylpiperazin-1-yl)-10H-thieno2,3-b1,5benzodiazepine; lanzac; Oleanz; 10H-Thieno[2,3-b][1,5]benzodiazepine, 2-methyl-4-(4-methyl-1-piperazinyl)-; 2-Methyl-4-(4-methylpiperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepin; Oliza; MFCD00866702; EINECS 200-835-2

物化性质

• 密度: 1.3±0.1 g/cm3
• 沸点: 476.0±55.0 °C at 760 mmHg
• 熔点: 195°C
• 分子式: C₁₇H₂₀N₄S
• 分子量: 312.432
• 闪点: 241.7±31.5 °C
• 精确质量: 312.140869
• PSA: 59.11000
• LogP: 2.18
• 外观性状: 淡黄色结晶粉末
• 蒸汽压: 0.0±1.2 mmHg at 25°C
• 折射率: 1.709
• 储存条件: -20°C Freezer
• 分子结构:

  1、 摩尔折射率：92.15

  2、 摩尔体积（cm³/mol）：235.9

  3、 等张比容（90.2K）：633.7

  4、 表面张力（dyne/cm）：52.0

  5、 极化率（10-24cm3）：36.53

• 计算化学:

  1.疏水参数计算参考值（XlogP）:2.8

  2.氢键供体数量:1

  3.氢键受体数量:5

  4.可旋转化学键数量:1

  5.互变异构体数量:3

  6.拓扑分子极性表面积56.2

  7.重原子数量:22

  8.表面电荷:0

  9.复杂度:543

  10.同位素原子数量:0

  11.确定原子立构中心数量:0

  12.不确定原子立构中心数量:0

  13.确定化学键立构中心数量:0

  14.不确定化学键立构中心数量:0

  15.共价键单元数量:1

• 更多:

  1.性状：从乙腈结晶。

  2.熔点：195℃。

生物活性

• 描述: Olanzapine(LY170053)是5-HT2和D2受体高亲和性拮抗剂。
• 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
  信号通路 >> 自噬 >> 自噬
  信号通路 >> 自噬 >> 自噬
  研究领域 >> 神经疾病
• 参考文献:

  [1]. Cipriani A, Rendell JM, Geddes J. Olanzapine in long-term treatment for bipolar disorder. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD004367. doi: 10.1002/14651858.

  [2]. Meera Narasimhan, Travis O Bruce, and Prakash Masand. Review of olanzapine in the management of bipolar disorders. Neuropsychiatr Dis Treat. 2007 October; 3(5): 579-587.

  [3]. Vieta E. Olanzapine in bipolar disorder. Expert Opin Pharmacother. 2004 Jul;5(7):1613-9.

  [4]. Bymaster FP, Calligaro DO, Falcone JF et al. Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology. 1996 Feb;14(2):87-96.

  [5]. Moore NA, Tye NC, Axton MS, Risius FC. The behavioral pharmacology of olanzapine, a novel "atypical" antipsychotic agent. J Pharmacol Exp Ther. 1992 Aug;262(2):545-51.

MSDS

Olanzapine Revision number: 5 SAFETY DATA SHEET Section1. IDENTIFICATION Product name:Olanzapine Revision number:5 Section2. HAZARDS IDENTIFICATION GHS classification PHYSICAL HAZARDSNot classified HEALTH HAZARDS Acute toxicity (Oral)Category 3 Category 2 Skin corrosion/irritation Serious eye damage/eye irritationCategory 2A Not classified ENVIRONMENTAL HAZARDS GHS label elements, including precautionary statements Pictograms or hazard symbols Signal wordDanger Hazard statementsToxic if swallowed Causes skin irritation Causes serious eye irritation Precautionary statements: Do not eat, drink or smoke when using this product. [Prevention] Wash hands thoroughly after handling. Wear protective gloves/eye protection/face protection. [Response]IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. Rinse mouth. IF IN EYES: 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. IF ON SKIN: Gently wash with plenty of soap and water. If skin irritation occurs: Get medical advice/attention. Take off contaminated clothing and wash before reuse. [Storage]Store locked up. [Disposal]Dispose of contents/container through a waste management company authorized by the local government. Section3. COMPOSITION/INFORMATION ON INGREDIENTS Substance/mixture:Substance Olanzapine Components: Olanzapine Section3. COMPOSITION/INFORMATION ON INGREDIENTS Percent:>98.0%(GC)(T) CAS Number:132539-06-1 Synonyms:2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine Chemical Formula:C17H20N4S Section4. FIRST AID MEASURES Remove victim to fresh air and keep at rest in a position comfortable for breathing. Inhalation: Get medical advice/attention if you feel unwell. Remove/Take off immediately all contaminated clothing. Gently wash with plenty of Skin contact: soap and water. 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:Immediately call a POISON CENTER or doctor/physician. 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 Suitable extinguishingDry 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. 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 Use extra personal protective equipment (P3 filter respirator for toxic particles). Keep Personal precautions, protective equipment and people away from and upwind of spill/leak. Entry to non-involved personnel should emergency procedures: be controlled around the leakage area by 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 closed system if possible. 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 locked up. Store away from incompatible materials such as oxidizing agents. Heat-sensitive Packaging material:Comply with laws. Section8. EXPOSURE CONTROLS / PERSONAL PROTECTION Engineering controls:Install a closed system or local exhaust. Also install safety shower and eye bath. Personal protective equipment Olanzapine Section8. EXPOSURE CONTROLS / PERSONAL PROTECTION Respiratory protection: Dust respirator, self-contained breathing apparatus(SCBA), supplied air respirator, etc. Use respirators approved under appropriate government standards and follow local and national regulations. Hand protection:Impervious gloves. Eye protection:Safety goggles. A face-shield, if the situation requires. Skin and body protection: Impervious protective clothing. Protective boots, if the situation requires. Section9. PHYSICAL AND CHEMICAL PROPERTIES Solid Physical state (20°C): Form:Crystal- Powder Colour:Pale yellow - Deep yellow Odour:No data available pH: No data available Melting point/freezing point:194°C (dec.) Boiling point/range:No data available Flash point:No data available Flammability or explosive limits: Lower:No data available Upper:No data available Relative density:No data available Solubility(ies): [Water]Insoluble [Other solvents] Soluble:Hot acetone Log Pow:4.09 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), Sulfur oxides products: Section11. TOXICOLOGICAL INFORMATION Acute Toxicity:orl-man LDLo:7067 ug/kg Skin corrosion/irritation: No data available Serious eyeNo data available damage/irritation: Germ cell mutagenicity: No data available Carcinogenicity: IARC =No data available NTP =No data available Reproductive toxicity:No data available RTECS Number:XJ9007750 Section12. ECOLOGICAL INFORMATION Ecotoxicity: Fish:No data available No data available Crustacea: Algae:No data available Persistence / degradability: No data available BioaccumulativeNo data available potential(BCF): Mobility in soil Olanzapine Section12. ECOLOGICAL INFORMATION Log Pow:4.09 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:6.1: Toxic substance. UN-No:2811 Proper shipping name:Toxic solid, organic, n.o.s. Packing group:III 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

安全

• 符号: GHS07
• 信号词: Warning
• 危害声明: H315-H319
• 警示性声明: P305 + P351 + P338
• 危害码 (欧洲): Xi,Xn,F
• 风险声明 (欧洲): 36/38-36-20/21/22-11
• 安全声明 (欧洲): S22-S24/25
• 危险品运输编码: UN 2811 6.1 / PGIII
• WGK德国: 3
• 海关编码: 2934999090

合成路线

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制备

1. 4-氨基-2-甲基-10H-噻吩并[2,3-b][1,5]苯并二氮杂革盐酸盐和N-甲基哌嗪，在二甲亚砜和甲苯中，氮气保护下回流20h，得到奥氮平。

2. 2-氨基-3-氰基-5-甲基噻吩的制备

在反应瓶中加入硫21.8g(0.68mol)、丙醛47.3g(0.81mol)和DMA135ml,搅拌溶解,5~10ºC滴加三乙胺57.6g(0.61mol),约30min加完,于18~20ºC搅拌1h.滴加丙二腈45g(0.68mol)的DMF90ml溶液,约1h加完,继续于15~20ºC搅拌反应1h.将反应液倾入冰水中,产生黄色沉淀,稍放置,过滤,水洗,干燥,得黄色固体2-氨基-3-氰基-5-甲基噻吩70g,收率74.6%,mp99~100ºC.

3. 2-(邻硝基苯氨基)-3-氰基-5-甲基噻吩的制备

在反应瓶中加入邻氯硝基苯28.2g(0.2mol)、2-氨基-3-氰基-5-甲基噻吩27.6g(0.2mol)、LiOH12.4g(0.3mol)和DMF150ml,于70 ºC搅拌反应6h.冷却,倒入碎冰中,用二氯甲烷(500×3)提取,用2mol/L盐酸100ml洗,水(200ml×2)洗,无水MgSO4干燥,减压蒸除回收溶剂,剩余物用乙醇重结晶,得黄色结晶2-(邻硝基苯氨基)-3-氰基-5-甲基噻吩35g, 收率70%,mp99~101ºC.

4. 2-甲基-4-氨基-10H-噻吩并[2,3-b][1,5]苯二氮杂盐酸盐的制备

在反应瓶中加入乙醇600ml和2-(邻硝基苯氨基)-3-氰基-5-甲基噻吩60g(0.23mol),于50 ºC搅拌10min.于10min内加入二水氯化亚锡170g(0.75mol)的6mol/L盐酸500ml的溶液,搅拌回流1h.减压蒸除乙醇,自然冷却,析晶,过滤,用少量水洗滤饼,再用少量丙酮洗至呈黄色,抽干,干燥,得黄色固体2-甲基-4-氨基-10H-噻吩并[2,3-b][1,5]苯二氮杂盐酸盐50g,收率82%,mp>250ºC.

5. 奥氮平的合成

在反应瓶中加入2-甲基-4-氨基-10H-噻吩并[2,3-b][1,5]苯二氮杂盐酸盐50g(0.19mol)、无水哌嗪200g(2.3mol)、DMSO250ml和甲苯250ml,搅拌溶解,搅拌回流20h.冷至50 ºC,倾入冰水1000ml中,放置析晶,过滤,水洗,抽干,干燥,得黄色固体.将固体加到反应瓶中,再加入DMSO500ml、37%甲醛14.6g(0.18mol)和98%甲酸8.5g(0.18mol),于80 ºC搅拌2h.倾入冰水中析晶,过滤,水洗,干燥得粗品奥氮平50g,用乙醇500ml重结晶,得奥氮平纯品40g,收率68%,mp193~195 ºC.

海关

海关编码	2934999090
中文概述	2934999090. 其他杂环化合物. 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
Summary	2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%