51264-14-3

• 常用中文名：安吖啶
• 常用英文名：Amsacrine
• CAS号：51264-14-3
• 分子式：C₂₁H₁₉N₃O₃S
• 分子量：393.459
• 相关类别： 原料药 抗肿瘤药 抗代谢类抗肿瘤药
• 发布时间：2018-08-29 11:04:36
• 更新时间：2024-01-02 15:19:58
• Amsacrine 是肿瘤细胞 DNA 嵌入剂,还能抑制拓扑异构酶 II。

名称

• 中文名: 安吖啶
• 英文名: amsacrine
• 中文别名: N-[4-(9-吖啶基氨基)-3-甲氧基苯基]甲磺酰胺; 安啶; M-AMSA 溶液
• 英文别名: m-AMSA; meta-Amsacrine; Methanesulfonamide, N-[4-(9-acridinylamino)-3-methoxyphenyl]-; Amsacrine; 4'-(Acridinylamino)methanesulfon-m-anisidide; Amsidyl; AMSA P-D; Amekrin; EINECS 257-094-3; AMSA, M-; Methanesulfonamide, N-(4-(9-acridinylamino)-3-methoxyphenyl)-; Amsine; Amsidine; N-[4-(9-Acridinylamino)-3-methoxuphenyl]methanesulfonamide; N-[4-(9-Acridinylamino)-3-methoxyphenyl]methanesulfonamide; N-[4-(acridin-9-ylamino)-3-(methyloxy)phenyl]methanesulfonamide; N-[4-(acridin-9-ylamino)-3-methoxyphenyl]methanesulfonamide

物化性质

• 密度: 1.4±0.1 g/cm3
• 沸点: 563.0±60.0 °C at 760 mmHg
• 熔点: 230-240ºC
• 分子式: C₂₁H₁₉N₃O₃S
• 分子量: 393.459
• 闪点: 294.3±32.9 °C
• 精确质量: 393.114716
• PSA: 88.70000
• LogP: 2.12
• 外观性状: 白色固体
• 蒸汽压: 0.0±1.5 mmHg at 25°C
• 折射率: 1.723
• 储存条件:

  保持贮藏器密封、储存在阴凉、干燥的地方，确保工作间有良好的通风或排气装置

• 稳定性:

  如果遵照规格使用和储存则不会分解，未有已知危险反应

• 计算化学:

  1.疏水参数计算参考值（XlogP）:4

  2.氢键供体数量:2

  3.氢键受体数量:6

  4.可旋转化学键数量:5

  5.互变异构体数量:2

  6.拓扑分子极性表面积88.7

  7.重原子数量:28

  8.表面电荷:0

  9.复杂度:601

  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：未确定

  2. 密度（g/mL,25ºC）：未确定

  3. 相对蒸汽密度（g/mL,空气=1）： 未确定

  4. 熔点（ºC）：未确定

  5. 沸点（ºC）：未确定

  6. 沸点（ºC，12mm hg）：未确定

  7. 折射率：未确定

  8. 闪点（°C）：未确定

  9. 比旋光度（ºC）：未确定

  10. 自燃点或引燃温度（ºC）： 未确定

  11. 蒸气压（kPa,25ºC）：未确定

  12. 饱和蒸气压（kPa,60ºC）：未确定

  13. 燃烧热（KJ/mol）：未确定

  14. 临界温度（ºC）：未确定

  15. 临界压力（KPa）：未确定

  16. 油水（辛醇/水）分配系数的对数值：未确定

  17. 爆炸上限（%,V/V）：未确定

  18. 爆炸下限（%,V/V）：未确定

  19. 溶解性：未确定

生物活性

• 描述: Amsacrine 是肿瘤细胞 DNA 嵌入剂,还能抑制拓扑异构酶 II。
• 相关类别:
  信号通路 >> 自噬 >> 自噬
  信号通路 >> 细胞周期/DNA损伤 >> 拓扑异构酶
  研究领域 >> 癌症
• 靶点:

  Topoisomerase II

• 体外研究: Amsacrine以浓度依赖性方式阻断HEK 293细胞和非洲爪蟾卵母细胞中的HERG电流,IC50值分别为209.4 nm和2.0μM。 Amsacrine引起激活(-7.6 mV)和失活(-7.6 mV)的电压依赖性的负向变化。通过amsacrine的HERG当前阻滞不依赖于频率[1]。对不同浓度m-AMSA的正常人淋巴细胞的体外研究显示,染色体畸变水平增加,范围从8％到100％,并且增加SCE,范围是研究的最低浓度的正常值的1.5倍(0.005μg/ mL)至正常值的12倍(0.25μg/ mL)[3]。 Amsacrine诱导的U937细胞凋亡的特征是caspase-9和caspase-3活化,细胞内Ca2 +浓度增加,线粒体去极化和MCL1下调。 Amsacrine通过降低其稳定性诱导MCL1下调。此外,amsacrine处理的U937细胞显示AKT降解和Ca2 +介导的ERK失活[4]。
• 体内研究: 在用不同剂量的安吖啶(0.5-12mg/kg)治疗的动物中,用9和12mg/kg治疗后,微核多色红细胞的频率显着增加。此外,本研究首次表明,amsacrine具有高致裂性发生率和低致气性发生率,而nocodazole在体内有丝分裂期具有高致气性和低致裂性发生率[2]。
• 动物实验: 在三个独立的实验中研究了Amsacrine。在第一个实验中，通过腹膜内注射0.5,1.5和4.5mg / kg的amsacrine处理动物，并在处理后24小时取样骨髓。在此采样时间的初步阴性MN结果导致使用30小时的采样时间用于安吖啶。因此，在第二个实验中，用0.5,1.5和4.5mg / kg的amsacrine处理小鼠，并在处理后30小时取样骨髓。通过参考早期研究选择安吖啶的剂量和采样时间，并且所选剂量在用于人化学疗法的剂量范围内。结果再次表明，小鼠骨髓中的微核率不受任何选定剂量的试验剂处理的影响，在30小时取样时间，因此，在第三个实验中，小鼠用6,9处理治疗后24和30小时取样12mg / kg的amsacrine和骨髓。
• 参考文献:

  [1]. Thomas D, et al. Inhibition of cardiac HERG currents by the DNA topoisomerase II inhibitor amsacrine: mode of action. Br J Pharmacol. 2004 Jun;142(3):485-94.

  [2]. Attia SM. Molecular cytogenetic evaluation of the mechanism of genotoxic potential of amsacrine and nocodazole in mouse bone marrow cells. J Appl Toxicol. 2013 Jun;33(6):426-33.

  [3]. Kao-Shan CS, et al. Cytogenetic effects of amsacrine on human lymphocytes in vivo and in vitro. Cancer Treat Rep. 1984 Jul-Aug;68(7-8):989-97.

  [4]. Lee YC, et al. Amsacrine-induced apoptosis of human leukemia U937 cells is mediated by the inhibition of AKT- and ERK-induced stabilization of MCL1. Apoptosis. 2016 Oct 19

毒性和生态

毒理学数据: 急性毒性LD50雄小鼠，雌小鼠(ml/m2):810,729口服。 盐酸安吖啶(Amsacrine Hydrochloride):C21H19N3O3S.HCL.。结晶，熔点197～199℃。急性毒性LD50小鼠(mg/kg):约60腹腔注射。 甲磺酸安吖啶(Amsacrine HydrochlorideC21H19N3O3S.CH3SO3H结 晶，熔点292～293℃。急性毒性LD50小鼠(mg/kg):约24腹腔注射。 生态学数据: 对水是稍微有危害的不要让未稀释或大量的产品接触地下水、水道或者污水系统，若无政府许可，勿将材料排入周围环境 CHEMICAL IDENTIFICATION RTECS NUMBER : PB1080000 CHEMICAL NAME : Methanesulfon-m-anisidide, 4'-(9-acridinylamino)- CAS REGISTRY NUMBER : 51264-14-3 BEILSTEIN REFERENCE NO. : 0500176 LAST UPDATED : 199801 DATA ITEMS CITED : 58 MOLECULAR FORMULA : C21-H19-N3-O3-S MOLECULAR WEIGHT : 393.49 WISWESSER LINE NOTATION : T C666 BNJ IMR BO1 DMSW1 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Human - man DOSE/DURATION : 5405 ug/kg/3H-C TOXIC EFFECTS : Blood - changes in bone marrow (not otherwise specified) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Human DOSE/DURATION : 12 mg/kg TOXIC EFFECTS : Vascular - thrombosis distant from injection site Gastrointestinal - nausea or vomiting Blood - other changes TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 53420 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 : 15470 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 : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 110 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 : 33700 ug/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 50 mg/kg TOXIC EFFECTS : Behavioral - food intake (animal) Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 6250 ug/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - weight loss or decreased weight gain TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Primate - monkey DOSE/DURATION : 10400 ug/kg TOXIC EFFECTS : Blood - changes in bone marrow (not otherwise specified) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 546 mg/kg/13W-I TOXIC EFFECTS : Blood - changes in bone marrow (not otherwise specified) Related to Chronic Data - death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 90 mg/kg/24W-I TOXIC EFFECTS : Blood - changes in bone marrow (not otherwise specified) Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - changes in testicular weight TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 69250 ug/kg/5D-I TOXIC EFFECTS : Behavioral - muscle contraction or spasticity Blood - pigmented or nucleated red blood cells Related to Chronic Data - death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 125 mg/kg/5D-I TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Blood - changes in bone marrow (not otherwise specified) Related to Chronic Data - death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 1950 ug/kg/5D-I TOXIC EFFECTS : Blood - hemorrhage Blood - changes in bone marrow (not otherwise specified) Blood - changes in leukocyte (WBC) count TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Primate - monkey DOSE/DURATION : 13 mg/kg/5D-I TOXIC EFFECTS : Blood - changes in bone marrow (not otherwise specified) Blood - changes in leukocyte (WBC) count TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 30 mg/kg/24W-I TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Gastrointestinal - tumors Skin and Appendages - tumors TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous DOSE : 6486 ug/kg SEX/DURATION : male 3 week(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 8 mg/kg SEX/DURATION : female 6-9 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal DOSE : 15 mg/kg SEX/DURATION : male 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) TYPE OF TEST : Micronucleus test TYPE OF TEST : DNA damage TYPE OF TEST : Cytogenetic analysis MUTATION DATA TYPE OF TEST : DNA damage TEST SYSTEM : Mammal - species unspecified Lymphocyte DOSE/DURATION : 54 umol/L REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 38,1300,1978 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X6337 No. of Facilities: 7 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 14 (estimated) No. of Female Employees: 14 (estimated)

安全

• 危险品运输编码: UN 3249
• 包装等级: III
• 危险类别: 6.1(b)
• 海关编码: 2935009090

制备

邻甲氧基对硝基苯胺和酰氯反应，对氨基酰胺化进行保护，还原硝基为氨基，以甲磺酰氯对该氨基进行酰化使形成甲磺酰胺基，再选择性水解脱去1位氨基上的保护基，最后和9-氯吖啶反应，得到安吖啶。

海关

海关编码	2935009090
中文概述	2935009090 其他磺（酰）胺. 增值税率:17.0% 退税率:9.0% 监管条件:无 最惠国关税:6.5% 普通关税:35.0%
申报要素	品名, 成分含量, 用途
Summary	2935009090 other sulphonamides VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:35.0%