中文名 | 克拉夫定 |
英文名 | 1-((2S,3R,4S,5S)-3-fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione |
别名 | 克拉夫定 克利夫定 1-(2'-脱氧-2'-氟-L-阿拉伯呋喃糖基)-5-甲基尿嘧啶 |
英文别名 | Levovir Clevudine CLEVUDINE 2'-Fluoro-5-methylarabinosyluracil 1-(2''-DEOXY-2''-FLUORO--L-ARABINOFURANOSYL)-5-METHYLURACIL 1-(2'-DEOXY-2'-FLUORO-BETA-L-ARABINOFURANOSYL)-5-METHYLURACIL 1-[(2S,3R,4S,5S)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione 1-[(2S,3R,4S,5S)-3-fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-5-methyl-pyrimidine-2,4-dione 1-((2S,3R,4S,5S)-3-fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione |
CAS | 163252-36-6 |
EINECS | 200-001-2 |
化学式 | C10H13FN2O5 |
分子量 | 260.22 |
密度 | 1.55±0.1 g/cm3(Predicted) |
熔点 | 184-185° |
比旋光度 | D25 -111.77° (c = 0.23 in methanol) |
溶解度 | DMSO (微溶) 、甲醇 (微溶) |
酸度系数 | 9.55±0.10(Predicted) |
存储条件 | under inert gas (nitrogen or Argon) at 2-8°C |
外观 | 固体 |
颜色 | White |
靶点 | DNA polymerase ;RNA polymerase |
体外研究 | Clevudine是一种有效的抗HBV剂(在HepG22.2.15细胞中EC 50为0.1 μM)以及抗EB病毒剂,在多种细胞系,包括MT2,CEM,H1和HepG22.2.15和骨髓祖细胞具有低的细胞毒性。Clevudine被细胞由细胞中的胸苷激酶以及脱氧胞苷激酶代谢为磷酸形式,及随后的二磷酸和三磷酸。Clevudine是已知特异性作用于病毒DNA合成的,其三磷酸以剂量依赖的方式抑制HBV DNA的合成而不被掺入到DNA或链终止。 Clevudine导致在这些类似物的二磷酸和三磷酸代谢物的增加。Clevudine单磷酸(L-FMAUMP)是D-异构体的较弱的配体。 在细胞培养中Clevudine很容易被磷酸化为5'-三磷酸形式化合物,这涉及Clevudine的作用机制。 |
体内研究 | Clevudine以剂量依赖方式导致病毒复发的延迟中,在土拨鼠模型中减少了共价闭合环状DNA的损失。 Clevudine(10毫克/千克,IP)与 Emtricitabine (30毫克/千克,IP)联用导致土拨鼠中病毒复制的快速显着的抑制作用,血清WHV DNA下降10的4次方。在WHV感染的土拨鼠中,Clevudine(10毫克/公斤,腹腔注射)与 Emtricitabine (30毫克/千克,IP)联用导致肝脏和血液中有效且持久的抗嗜肝病毒作用。 |
参考资料 展开查看 | 1: Anderson DL. Clevudine for hepatitis B. Drugs Today (Barc). 2009 May;45(5):331-50. doi: 10.1358/dot.2009.45.5.1354223. Review. PubMed PMID: 19584963. 2: Lau GK, Leung N. Forty-eight weeks treatment with clevudine 30 mg qd versus lamivudine 100 mg qd for chronic hepatitis B infection: a double-blind randomized study. Korean J Hepatol. 2010 Sep;16(3):315-20. doi: 10.3350/kjhep.2010.16.3.315. PubMed PMID: 20924215; PubMed Central PMCID: PMC3304600. 3: Kocic I. Clevudine University of Georgia/Abbott/Bukwang/Triangle/Yale University. Curr Opin Investig Drugs. 2000 Nov;1(3):308-13. Review. PubMed PMID: 11249713. 4: Yoo BC, Kim JH, Kim TH, Koh KC, Um SH, Kim YS, Lee KS, Han BH, Chon CY, Han JY, Ryu SH, Kim HC, Byun KS, Hwang SG, Kim BI, Cho M, Yoo K, Lee HJ, Hwang JS, Kim YS, Lee YS, Choi SK, Lee YJ, Yang JM, Park JW, Lee MS, Kim DG, Chung YH, Cho SH, Choi JY, Kweon YO, Lee HY, Jeong SH, Yoo HW, Lee HS. Clevudine is highly efficacious in hepatitis B e antigen-negative chronic hepatitis B with durable off-therapy viral suppression. Hepatology. 2007 Oct;46(4):1041-8. PubMed PMID: 17647293. 5: Asselah T, Lada O, Moucari R, Marcellin P. Clevudine: a promising therapy for the treatment of chronic hepatitis B. Expert Opin Investig Drugs. 2008 Dec;17(12):1963-74. doi: 10.1517/13543780802535760 . Review. PubMed PMID: 19012511. 6: Hui CK, Lau GK. Clevudine for the treatment of chronic hepatitis B virus infection. Expert Opin Investig Drugs. 2005 Oct;14(10):1277-84. Review. PubMed PMID: 16185170. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 3.843 ml | 19.215 ml | 38.429 ml |
5 mM | 0.769 ml | 3.843 ml | 7.686 ml |
10 mM | 0.384 ml | 1.921 ml | 3.843 ml |
5 mM | 0.077 ml | 0.384 ml | 0.769 ml |