阿莫地喹

阿莫地喹用途

Amodiaquine (Amodiaquin) 是一种4-氨基喹啉类抗疟剂,是一种有效的具有口服活性的组胺 N-甲基转移酶 (histamine N-methyltransferase) 抑制剂。Amodiaquine 也是一种 Nurr1 激动剂,可特异性结合 Nurr1 的配体结合域,EC50 为 ~20 μM。抗炎作用。

阿莫地喹名称

[ CAS 号 ]:
86-42-0

[ 中文名 ]:
阿莫地喹

[ 英文名 ]:
Amodiaquine

[中文别名 ]:

氨酚喹啉

[英文别名 ]:

SN 10,751
CAM-AQI
Camoquinal
Camoquine
EINECS 201-669-3
MFCD00552927
Camoquin
Flavoquine
Miaquin
aminodiaquine

阿莫地喹生物活性

[ 描述 ]:

[ 相关类别 ]:

研究领域 >> 感染

信号通路 >> 表观遗传学 >> 组蛋白甲基转移酶

研究领域 >> 炎症/免疫

研究领域 >> 神经疾病

[ 靶点 ]

EC50: ~20 μM (Nurr1-LBD (ligand binding domain))[1] Histamine N-methyltransferase[3]

[体外研究]

阿莫地喹(10-20μM；4小时)治疗以剂量依赖性方式抑制LPS诱导的促炎性细胞因子(IL-1β、IL-6、TNF-α和iNOS)的表达[1]。阿莫地喹(5μM；24小时)显著抑制神经毒素(6-OHDA诱导的原代多巴胺细胞死亡,通过TH+神经元数量和多巴胺摄取量检测。阿莫地喹对大鼠PC12细胞也有神经保护作用[1]。RT-PCR[1]细胞系：原代小胶质细胞浓度：10µM,15µM,20µM孵育时间：4h。结果：LPS诱导的促炎性细胞因子(IL-1β、IL-6、TNF-α和iNOS)的表达呈剂量依赖性。

[体内研究]

阿莫地喹(40 mg/kg；腹腔注射；每日；连续3天；雄性ICR小鼠)治疗可减少血周小胶质细胞/巨噬细胞和星形胶质细胞的活化。阿莫地喹还可抑制脑出血诱导的IL-1β、CCL2和CXCL2的mRNA表达,改善小鼠运动功能障碍[2]。动物模型：雄性ICR小鼠(8-10周龄)诱发脊髓内出血[2]剂量：40mg/kg腹腔注射；每日；连续3天结果：血周小胶质细胞/巨噬细胞和星形胶质细胞的活化减少。

[参考文献]

[1]. Chun-Hyung Kim, et al. Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson's disease. Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):8756-61.

[2]. Keita Kinoshita, et al. A Nurr1 agonist amodiaquine attenuates inflammatory events and neurological deficits in a mouse model of intracerebral hemorrhage. J Neuroimmunol. 2019 May 15;330:48-54.

[3]. Akira Yokoyama, et al. Effect of amodiaquine, a histamine N-methyltransferase inhibitor, on, Propionibacterium acnes and lipopolysaccharide-induced hepatitis in mice. Eur J Pharmacol. 2007 Mar 8;558(1-3):179-84.

[4]. M T HOEKENGA. The treatment of acute malaria with single oral doses of amodiaquin, chloroquine, hydroxychloroquine and pyrimethamine. Am J Trop Med Hyg. 1954 Sep;3(5):833-8.

阿莫地喹物理化学性质

[ 密度 ]:
1.3±0.1 g/cm3

[ 沸点 ]:
478.0±45.0 °C at 760 mmHg

[ 熔点 ]:
208°C

[ 分子式 ]:
C₂₀H₂₂ClN₃O

[ 分子量 ]:
355.861

[ 闪点 ]:
242.9±28.7 °C

[ 精确质量 ]:
355.145142

[ PSA ]:
48.39000

[ LogP ]:
4.77

[ 外观性状 ]:
水晶般的固体

[ 蒸汽压 ]:
0.0±1.2 mmHg at 25°C

[ 折射率 ]:
1.669

[ 储存条件 ]:
-20°C Freezer

阿莫地喹毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: GO7300000

CHEMICAL NAME :: o-Cresol, 4-((7-chloro-4-quinolyl)amino)-alpha-(diethylamino)-

CAS REGISTRY NUMBER :: 86-42-0

BEILSTEIN REFERENCE NO. :: 0300962

LAST UPDATED :: 199612

DATA ITEMS CITED :: 7

MOLECULAR FORMULA :: C20-H22-Cl-N3-O

MOLECULAR WEIGHT :: 355.90

WISWESSER LINE NOTATION :: T66 BNJ EMR DQ C1N2&2& IG

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 72 mg/kg/7W-I

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - pulmonary emboli Liver - other changes Blood - agranulocytosis

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 20 mg/kg/25D-I

TOXIC EFFECTS :: Blood - thrombocytopenia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 29 mg/kg/25D-I

TOXIC EFFECTS :: Blood - thrombocytopenia

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 800 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 :: 550 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 - mouse

DOSE/DURATION :: 225 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

MUTATION DATA

TYPE OF TEST :: Phage inhibition capacity

TEST SYSTEM :: Bacteria - Escherichia coli

DOSE/DURATION :: 5 mg/plate

REFERENCE :: MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 222,311,1989

阿莫地喹安全信息

[ 安全声明 (欧洲) ]:
S22-S24/25-S8

[ WGK德国 ]:
3

[ 海关编码 ]:
2933499090

阿莫地喹合成路线

详细合成路线

阿莫地喹上下游产品

阿莫地喹上游产品

阿莫地喹下游产品

阿莫地喹海关

[ 海关编码 ]: 2933499090

[ 中文概述 ]:
2933499090. 其他含喹琳或异喹啉环系的化合物〔但未进一步稠合的〕. 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 ]:
2933499090. other compounds containing in the structure a quinoline or isoquinoline ring-system (whether or not hydrogenated), not further fused. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%