利巴韦林

利巴韦林用途

Ribavirin是广谱的抗病毒药,可抑制HCV,HIVl,RSV等病毒。

利巴韦林作用

1、利巴韦林在红细胞中磷酸化，生成三氮唑核苷单磷酸、二磷酸及三磷酸。其中三氮唑核苷单磷酸是肌苷单磷酸脱氢酶的强抑制剂，可抑制细胞鸟苷酸的合成，降低细胞鸟苷酸三磷酸化，阻断病毒核酸的合成。
2、三氮唑核苷三磷酸抑制流感病毒RNA聚合酶，干扰病毒复制。
3、三氮唑核苷三磷酸抑制病毒mRNA5’末端的合成和转录酶，从而抑制DNA和RNA合成。对多种病毒 (包括DNA型病毒和RNA型病毒) 有抑制作用。对流感、腺病毒肺炎、甲型肝炎、疱疹、麻疹等有防治作用，对流行性出血热也有效。
4、主要经尿以原形排泄，也有少量脱糖三氮唑核苷代谢产物，少量从粪便排出。

利巴韦林名称

[ CAS 号 ]:
36791-04-5

[ 中文名 ]:
利巴韦林

[ 英文名 ]:
Ribavirin

[中文别名 ]:

[英文别名 ]:

RTC
1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide
Ribavirin
UNII-49717AWG6K
MFCD00058564
rtca
Rebetol
Ravanex
Virazide
Virazole

利巴韦林生物活性

[ 描述 ]:

Ribavirin是广谱的抗病毒药,可抑制HCV,HIVl,RSV等病毒。

[ 相关类别 ]:

信号通路 >> 抗感染 >> HCV

信号通路 >> 抗感染 >> RSV

研究领域 >> 感染

[体外研究]

利巴韦林(5,10和20μM)对未刺激的小胶质细胞中的细胞活力和亚硝酸盐水平均不产生任何显着影响。用5,10和20μM利巴韦林处理LPS刺激的小胶质细胞分别诱导NO 2水平降低43％(p <0.05),53％(p <0.05)和59％(p <0.05)。利巴韦林(10 mM)在未刺激的培养物中显着降低细胞表面积,但在LPS刺激的小胶质细胞中显着降低细胞表面积(32％,p <0.05)[3]。利巴韦林对DENV具有活性,在A549细胞中EC50为3μM,并且CM-10-18与利巴韦林的组合在病毒复制的减少中表现出明显的增强[4]。

[体内研究]

给予JAT联合干扰素和利巴韦林可显着降低ALT,AST活性和胆红素水平(p <0.01)。单独的JAT,干扰素或利巴韦林与CCl4,肝脏似乎表现出一些针对CCl4的肝脏保护作用,正如肝线的存在,没有坏死和较少的脂肪浸润所证明的。分别或组合用JAT,Peg-干扰素和利巴韦林处理的组显示TGF-β和Bax的表达降低。在通过干扰素,利巴韦林和JAT的三重组合治疗的组中,p53的表达水平显着降低[1]。利巴韦林胶囊(400mg利巴韦林)处理的Wistar大鼠显示活化素A显着降低,并且血清和肝脏水平的卵泡抑素显着增加。只有当利巴韦林与IFN-α或Peg-IFN-α联合使用时,利巴韦林才具有很强的抗病毒活性[2]。利巴韦林(40mg/kg,口服)显着改善CM-10-18在小鼠中的抗病毒功效。利巴韦林抑制培养细胞中的DENV病毒感染,但它在减少单药治疗中的病毒血症方面无效[4]。

[细胞实验]

利巴韦林对小胶质细胞活力的影响通过磺酰罗丹明B（SRB）化学敏感性测定来评估。简而言之，在存在或不存在利巴韦林的情况下，将LPS刺激的小神经胶质细胞温育48小时。然后，将细胞在10％（w / v）三氯乙酸中于4℃固定1小时，在自来水中漂洗并用1％乙酸（100μL/孔）中的0.4％（w / v）SRB染色。在室温（RT）下保持30分钟。然后将细胞在1％乙酸中漂洗三次以除去未结合的染色剂。每孔用200μL10mMTris碱（pH 10.5）提取蛋白质结合的染色剂。在540nm处读取光密度，在670nm处进行校正。结果表示为对照（未刺激/未处理的小神经胶质细胞）的百分比，其任意设定为100％。

[动物实验]

使用AG129小鼠中的登革热病毒血症模型（I型和II型干扰素受体缺陷）主要进行体内功效实验。每个实验每个给药组包含6只小鼠（7至8周龄）。通过ip注射以5×10 6 pfu /小鼠用DENV（血清型2，TSV01株）攻击小鼠。每隔12小时给予Imino糖两次，并且每天一次给予利巴韦林，感染后连续3天。在感染后3天抽取血样用于通过噬斑测定法测定血浆病毒滴度。

[参考文献]

[1]. Abdel-Hamid NM, et al. Synergistic Effects of Jerusalem Artichoke in Combination with Pegylated Interferon Alfa-2a and Ribavirin Against Hepatic Fibrosis in Rats. Asian Pac J Cancer Prev. 2016;17(4):1979-85.

[2]. Refaat B, et al. The effects of pegylated interferon-α and ribavirin on liver and serum concentrations of activin-A and follistatin in normal Wistar rat: a preliminary report. BMC Res Notes. 2015 Jun 26;8:265

[3]. Savic D, et al. Ribavirin shows immunomodulatory effects on activated microglia. Immunopharmacol Immunotoxicol. 2014 Dec;36(6):433-41

[4]. Chang J, et al. Combination of α-glucosidase inhibitor and ribavirin for the treatment of dengue virus infection in vitro and in vivo. Antiviral Res. 2011 Jan;89(1):26-34

[相关活性小分子]

利巴韦林物理化学性质

[ 密度 ]:
2.1±0.1 g/cm3

[ 沸点 ]:
639.8±65.0 °C at 760 mmHg

[ 熔点 ]:
174-176°C

[ 分子式 ]:
C₈H₁₂N₄O₅

[ 分子量 ]:
244.205

[ 闪点 ]:
340.7±34.3 °C

[ 精确质量 ]:
244.080765

[ PSA ]:
143.72000

[ LogP ]:
-2.26

[ 外观性状 ]:
无色固体

[ 蒸汽压 ]:
0.0±2.0 mmHg at 25°C

[ 折射率 ]:
1.823

[ 储存条件 ]:
2-8°C

[ 水溶解性 ]:
>=10 G/100 ML AT 19 ºC

利巴韦林MSDS

详细MSDS(安全技术说明书)

利巴韦林毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: XZ4250000

CHEMICAL NAME :: 1,2,4-Triazole-3-carboxamide, 1-beta-D-ribofuranosyl-

CAS REGISTRY NUMBER :: 36791-04-5

LAST UPDATED :: 199612

DATA ITEMS CITED :: 32

MOLECULAR FORMULA :: C8-H12-N4-O5

MOLECULAR WEIGHT :: 244.24

WISWESSER LINE NOTATION :: T5OTJ B1Q CQ DQ E- AT5NN DNJ CVZ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2700 mg/kg

TOXIC EFFECTS :: Tumorigenic - active as anti-cancer agent

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 4 gm/kg

TOXIC EFFECTS :: Tumorigenic - active as anti-cancer agent

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1300 mg/kg

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

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 1500 mg/kg

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Kidney, Ureter, Bladder - other changes Blood - hemorrhage

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 1 gm/kg/10D-I

TOXIC EFFECTS :: Blood - normocytic anemia Blood - changes in bone marrow (not otherwise specified) Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - cat

DOSE/DURATION :: 220 mg/kg/10D-I

TOXIC EFFECTS :: Blood - changes in platelet count Nutritional and Gross Metabolic - changes in calcium

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - cat

DOSE/DURATION :: 220 mg/kg/10D-I

TOXIC EFFECTS :: Blood - changes in platelet count Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Mammal - cat

DOSE/DURATION :: 440 mg/kg/10D-I

TOXIC EFFECTS :: Blood - changes in bone marrow (not otherwise specified) Blood - changes in platelet count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 25 mg/kg

SEX/DURATION :: female 9 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 37500 ug/kg

SEX/DURATION :: female 9 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 3150 mg/kg

SEX/DURATION :: male 90 day(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 :: Oral

DOSE :: 9 gm/kg

SEX/DURATION :: male 60 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 25 mg/kg

SEX/DURATION :: female 10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 3750 ug/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2500 ug/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 2500 ug/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - eye/ear

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 5 mg/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 2500 ug/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 5 mg/kg

SEX/DURATION :: female 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 5 mg/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 5 mg/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :: Mutation test systems - not otherwise specified

TEST SYSTEM :: Rodent - rabbit Kidney

DOSE/DURATION :: 4900 ug/L

REFERENCE :: BCPCA6 Biochemical Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1958- Volume(issue)/page/year: 38,1771,1989 *** REVIEWS *** TOXICOLOGY REVIEW JACTDZ Journal of the American College of Toxicology. (Mary Ann Liebert, Inc., 1651 Third Ave., New York, NY 10128) V.1-12, 1982-1993. Discontinued. Volume(issue)/page/year: 9(5),551,1990

利巴韦林安全信息

[ 符号 ]:

GHS08

[ 信号词 ]:
Danger

[ 危害声明 ]:
H360

[ 警示性声明 ]:
P201-P280-P308 + P313

[ 个人防护装备 ]:
Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ 危害码 (欧洲) ]:
Xi

[ 风险声明 (欧洲) ]:
R61

[ 安全声明 (欧洲) ]:
53-22-45-37/39-26

[ 危险品运输编码 ]:
UN 3152 9/PG 2

[ WGK德国 ]:
3

[ RTECS号 ]:
XZ4250000

[ 包装等级 ]:
II

[ 危险类别 ]:
9

[ 海关编码 ]:
2933290090

利巴韦林合成路线

详细合成路线

利巴韦林上下游产品

利巴韦林上游产品

利巴韦林下游产品

利巴韦林制备

以核苷或核苷酸为原料
先将鸟苷和鸟苷酸在冰醋酸和醋酐的作用下水解，生成核糖-1-磷酸，再在双-对硝基苯酚的催化下，与三叠氮缩酰胺反应生成缩合物，经氨解即得。
鸟苷（或鸟苷酸）[乙酐，冰醋酸]→[水解]核糖-1-磷酸[双-(对硝基苯酚）-磷酸酯]→[三叠氮羧基酰胺]缩合物[氨解]→三唑核苷
酶合成法
先将鸟苷和鸟苷酸在嘧啶核苷磷酸化酶的作用下水解，生成核糖-1-磷酸，再在嘌呤核苷磷酸化酶的作用下与三叠氮缩酰胺反应直接生成三氮唑核苷。
鸟苷（或鸟苷酸）[嘧啶核苷磷酸化酶]→核糖-1-核酸[嘌呤核苷酸化酶]→三唑核苷。

利巴韦林海关

[ 海关编码 ]: 2933290090

[ 中文概述 ]:
2933290090. 其他结构含非稠合咪唑环的化合物. 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 ]:
2933290090. other compounds containing an unfused imidazole ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

利巴韦林文献

Genetic and pharmacologic inhibition of eIF4E reduces breast cancer cell migration, invasion, and metastasis.

Cancer Res. 75(6) , 1102-12, (2015)

The translation initiation factor eIF4E is an oncogene that is commonly overexpressed in primary breast cancers and metastases. In this article, we report that a pharmacologic inhibitor of eIF4E funct...

An integrated biological approach to guide the development of metal-chelating inhibitors of influenza virus PA endonuclease.

Mol. Pharmacol. 87(2) , 323-37, (2015)

The influenza virus PA endonuclease, which cleaves capped cellular pre-mRNAs to prime viral mRNA synthesis, is a promising target for novel anti-influenza virus therapeutics. The catalytic center of t...

Antiviral and antitumor activities of the lectin extracted from Aspidistra elatior.

Z. Naturforsch., C, J. Biosci. 70 , 7-13, (2015)

Lectins, a group of highly diverse proteins of non-immune origin and are ubiquitously distributed in plants, animals and fungi, have multiple significant biological functions, such as anti-fungal, ant...

更多文献