321-64-2

• 常用中文名：他克林
• 常用英文名：Tacrine
• CAS号：321-64-2
• 分子式：C₁₃H₁₄N₂
• 分子量：198.264
• 相关类别： 原料药 专科用药 解毒药
• 发布时间：2018-08-05 19:33:26
• 更新时间：2024-01-02 09:50:28
• 他克林是一种有效的乙酰胆碱酯酶(AChE)抑制剂(IC50=109 nM),也可作为CYP1A2底物药物。他克林在某些个体中表现出一定的肝毒性。他克林可用于研究阿尔茨海默病[1][2][3]。

名称

• 中文名: 9-胺-1,2,3,4-四氢盐酸氯酯
• 英文名: tacrine
• 中文别名: 他克林
• 英文别名: EINECS 206-291-2; MFCD00046923; 9-Acridinamine, 1,2,3,4-tetrahydro-; 1,2,3,4-TETRAHYDRO-9-ACRIDINAMINE; 9-Amino-1,2,3,4-tetrahydroacridine; Tetrahydroaminocrine; Tenakrin; 1,2,3,4-tetrahydro-5-aminoacridine; Cognex; 4-Amino-2,3-tetramethylenequinoline; Tetrahydroaminocrin; 1,2,3,4-tetrahydro-9-amino-acridine; Tetrahydroaminacrine; 1,2,3,4-tetrahdyroacridin-9-amine; 1,2,3,4-tetrahydroacridin-9-amine; Romotal; Tetrahydroaminoacridine; Tacrine

物化性质

• 密度: 1.3±0.1 g/cm3
• 沸点: 353.8±42.0 °C at 760 mmHg
• 熔点: 283-284ºC
• 分子式: C₁₃H₁₄N₂
• 分子量: 198.264
• 闪点: 167.8±27.9 °C
• 精确质量: 198.115692
• PSA: 38.91000
• LogP: 1.78
• 外观性状: 白色至黄色固体
• 蒸汽压: 0.0±0.8 mmHg at 25°C
• 折射率: 1.682
• 储存条件: 室温，干燥，避光
• 计算化学:

  1.疏水参数计算参考值（XlogP）:无

  2.氢键供体数量:1

  3.氢键受体数量:2

  4.可旋转化学键数量:0

  5.互变异构体数量:10

  6.拓扑分子极性表面积:38.9

  7.重原子数量:15

  8.表面电荷:0

  9.复杂度:229

  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

生物活性

• 描述: 他克林是一种有效的乙酰胆碱酯酶(AChE)抑制剂(IC50=109 nM),也可作为CYP1A2底物药物。他克林在某些个体中表现出一定的肝毒性。他克林可用于研究阿尔茨海默病[1][2][3]。
• 相关类别:
  研究领域 >> 神经疾病
  信号通路 >> 神经信号通路 >> 疼痛
• 靶点:

  IC50: 109 nM (AChE)[3]

• 参考文献:

  [1]. Patocka J, et al. Possible role of hydroxylated metabolites of tacrine in drug toxicity and therapy of Alzheimer's disease. Curr Drug Metab. 2008;9(4):332-335.

  [2]. Bhatt S, et al. Assessment of the CYP1A2 Inhibition-Mediated Drug Interaction Potential for Pinocembrin Using In Silico, In Vitro, and In Vivo Approaches. ACS Omega. 2022;7(23):20321-20331. Published 2022 Jun 2.

  [3]. Romero A, et al. Novel tacrine-related drugs as potential candidates for the treatment of Alzheimer's disease. Bioorg Med Chem Lett. 2013;23(7):1916-1922.

MSDS

Name: 9-Amino-1 2 3 4-tetrahydroacridine hydrochloride hydrate 99+% (tlc) Material Safety Data Sheet Synonym: THA; Tacrine hydrochlorid CAS: 321-64-2 Section 1 - Chemical Product MSDS Name:9-Amino-1 2 3 4-tetrahydroacridine hydrochloride hydrate 99+% (tlc) Material Safety Data Sheet Synonym:THA; Tacrine hydrochlorid Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS CAS# Chemical Name content EINECS# 321-64-2 9-Amino-1,2,3,4-tetrahydroacridine hyd 99+% 206-291-2 Hazard Symbols: T Risk Phrases: 25 Section 3 - HAZARDS IDENTIFICATION EMERGENCY OVERVIEW Toxic if swallowed.The toxicological properties of this material have not been fully investigated. Potential Health Effects Eye: May cause eye irritation. Skin: May cause skin irritation. Ingestion: Harmful if swallowed. Inhalation: May cause respiratory tract irritation. Chronic: No information found. Section 4 - FIRST AID MEASURES Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid. Skin: Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Ingestion: If victim is conscious and alert, give 2-4 cupfuls of milk or water. Get medical aid immediately. Wash mouth out with water. Inhalation: Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid. Notes to Physician: Section 5 - FIRE FIGHTING MEASURES General Information: As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. Extinguishing Media: Use water spray, dry chemical, carbon dioxide, or chemical foam. Section 6 - ACCIDENTAL RELEASE MEASURES General Information: Use proper personal protective equipment as indicated in Section 8. Spills/Leaks: Vacuum or sweep up material and place into a suitable disposal container. Section 7 - HANDLING and STORAGE Handling: Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Use with adequate ventilation. Avoid contact with skin and eyes. Avoid ingestion and inhalation. Storage: Store in a cool, dry place. Store in a tightly closed container. Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION Engineering Controls: Use adequate ventilation to keep airborne concentrations low. Exposure Limits CAS# 321-64-2: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166. Skin: Wear appropriate protective gloves to prevent skin exposure. Clothing: Wear appropriate protective clothing to prevent skin exposure. Respirators: Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced. Section 9 - PHYSICAL AND CHEMICAL PROPERTIES Physical State: Solid Color: white Odor: Not available. pH: Not available. Vapor Pressure: Not available. Viscosity: Not available. Boiling Point: Not available. Freezing/Melting Point: 283 - 284 deg C Autoignition Temperature: Not available. Flash Point: Not available. Explosion Limits, lower: Not available. Explosion Limits, upper: Not available. Decomposition Temperature: Solubility in water: soluble in water Specific Gravity/Density: Molecular Formula: C13H14N2.HCl.xH2O Molecular Weight: 234.72 Section 10 - STABILITY AND REACTIVITY Chemical Stability: Stable under normal temperatures and pressures. Conditions to Avoid: Incompatible materials. Incompatibilities with Other Materials: Strong oxidizing agents, acid chlorides, acid anhydrides. Hazardous Decomposition Products: Hydrogen chloride, nitrogen oxides, carbon monoxide, carbon dioxide. Hazardous Polymerization: Has not been reported. Section 11 - TOXICOLOGICAL INFORMATION RTECS#: CAS# 321-64-2: AR9532100 LD50/LC50: CAS# 321-64-2: Oral, mouse: LD50 = 39800 ug/kg; Oral, rat: LD50 = 70 mg/kg. Carcinogenicity: 9-Amino-1,2,3,4-tetrahydroacridine hydrochloride hydrate - Not listed by ACGIH, IARC, or NTP. Other: See actual entry in RTECS for complete information. Section 12 - ECOLOGICAL INFORMATION Section 13 - DISPOSAL CONSIDERATIONS Dispose of in a manner consistent with federal, state, and local regulations. Section 14 - TRANSPORT INFORMATION IATA Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.* Hazard Class: 6.1 UN Number: 2811 Packing Group: III IMO Shipping Name: TOXIC SOLID, ORGANIC, N.O.S. Hazard Class: 6.1 UN Number: 2811 Packing Group: III RID/ADR Shipping Name: TOXIC SOLID, ORGANIC, N.O.S. Hazard Class: 6.1 UN Number: 2811 Packing group: III Section 15 - REGULATORY INFORMATION European/International Regulations European Labeling in Accordance with EC Directives Hazard Symbols: T Risk Phrases: R 25 Toxic if swallowed. Safety Phrases: S 28A After contact with skin, wash immediately with plenty of water. S 45 In case of accident or if you feel unwell, seek medical advice immediately (show the label where possible). WGK (Water Danger/Protection) CAS# 321-64-2: No information available. Canada None of the chemicals in this product are listed on the DSL/NDSL list. CAS# 321-64-2 is not listed on Canada's Ingredient Disclosure List. US FEDERAL TSCA CAS# 321-64-2 is not listed on the TSCA inventory. It is for research and development use only. SECTION 16 - ADDITIONAL INFORMATION N/A

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : AR9532100 CHEMICAL NAME : Acridine, 1,2,3,4-tetrahydro-9-amino- CAS REGISTRY NUMBER : 321-64-2 BEILSTEIN REFERENCE NO. : 0147610 LAST UPDATED : 199707 DATA ITEMS CITED : 17 MOLECULAR FORMULA : C13-H14-N2 MOLECULAR WEIGHT : 198.29 WISWESSER LINE NOTATION : T C666 BNT&&J IZ HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 294 mg/kg/14W-I TOXIC EFFECTS : Liver - fatty liver degeneration Liver - liver function tests impaired Blood - changes in cell count (unspecified) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 84 mg/kg/6W-I TOXIC EFFECTS : Liver - hepatitis (hepatocellular necrosis), zonal Liver - liver function tests impaired TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 176 mg/kg/7W-I TOXIC EFFECTS : Gastrointestinal - nausea or vomiting Liver - liver function tests impaired TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 70 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 : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 30 mg/kg TOXIC EFFECTS : Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - true cholinesterase TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 20 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 : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 34 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 : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 39800 ug/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 : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 20 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 : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 25 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 : Intramuscular SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 29 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 : Unreported SPECIES OBSERVED : Mammal - species unspecified DOSE/DURATION : 31 mg/kg TOXIC EFFECTS : Behavioral - euphoria Behavioral - antipsychotic TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 620 mg/kg/18W-C TOXIC EFFECTS : Nutritional and Gross Metabolic - weight loss or decreased weight gain TYPE OF TEST : Cytogenetic analysis MUTATION DATA TEST SYSTEM : Rodent - mouse DOSE/DURATION : 100 mg/kg REFERENCE : ACNSAX Activitas Nervosa Superior. (Avicenum, Malostranske nam. 28, Prague 1, Czechoslovakia) V.1- 1959- Volume(issue)/page/year: 26,84,1984

安全

• 危害码 (欧洲): T
• 风险声明 (欧洲): R25
• 海关编码: 2933990090

合成路线

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制备

【方法一】
苯胺和羟胺及水合三氯乙醛反应后，再硫酸催化环合得靛红，收率 63.4%。靛红、过量的盐酸羟胺、乙酸钠三水合物和水，在60℃剧烈搅拌后室温放置过夜。过滤，乙醇-水重结晶，得靛红-3-肟，收率92%。靛红-3-肟加热至熔融，剧烈分解生成邻氨基苯甲腈，用乙醚溶解收集。蒸出乙醚后减压蒸馏得产品，收率86.8%，沸点112～114℃/0.8kPa，熔点48～50℃。邻氨基苯甲腈溶于环己酮，加入等摩尔的无水二氯化锌，搅拌回流。冷却过滤，固体用乙醚洗数次后，悬于水中。加30%氢氧化钠至强碱性，用二氯甲烷提取。提取液水洗，干燥，浓缩，用甲苯重结晶，得微黄色片状的他克林结晶，收率92.6%，熔点182～184℃。

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%