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
|
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 |
|
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
|
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 |
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
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LAST UPDATED :
-
199801
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DATA ITEMS CITED :
-
58
-
MOLECULAR FORMULA :
-
C21-H19-N3-O3-S
-
MOLECULAR WEIGHT :
-
393.49
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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)
|
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 |
【方法1】
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% |