ANTI-HIV AND ANTI-HBV ACTIVITIES OF L-2',3'-DIDEOXYNUCLEOSIDE ANALOGS - DDC, 5FDDC, 5-AZA DDC AND DDG

被引:0
|
作者
MANSOUR, TS
TSE, A
CHARRON, M
机构
[1] GLAXO WELLCOME PLC,DEPT VIROL,STEVENAGE SG1 2NY,HERTS,ENGLAND
[2] BIOCHEM THERAPEUT INC,LAVAL,PQ H7V 4A7,CANADA
关键词
D O I
暂无
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Dideoxynucleoside analogues are amongst the most important inhibitors of reverse transcriptase (RT), a key enzyme encoded by HIV and involved in its replication.(1) Compelling evidence has supported the notion that some analogues with the L-absolute configuration in the heterosubstituted nucleoside analogues are potent antiviral agents. (-)-2'-Deoxy-3'-thiacytidine(2) (3TC((TM)), lamivudine), its 5-fluoro analogue(3) (-)-FTC and (-)-dioxolane C ((-)-BCH-204)(4) are prototypes with beta-L-configuration possessing potent anti-HIV and anti-HBV activities. In particular, substantial selectivity is demonstrated with 3TC((M)), which is currently in advanced clinical trials for the treatment of AIDS and hepatitis-B infections.(5)
引用
收藏
页码:417 / 425
页数:9
相关论文
共 50 条
  • [41] Stereoselective syntheses of substituted pterocarpans with anti-HIV activity, and 5-aza-/5-thia-pterocarpan and 2-aryl-2,3-dihydrobenzofuran analogues
    Engler, TA
    LaTessa, KO
    Iyengar, R
    Chai, WY
    Agrios, K
    BIOORGANIC & MEDICINAL CHEMISTRY, 1996, 4 (10) : 1755 - 1769
  • [42] D- and L-2′,3′-didehydro-2′,3′-dideoxy-3′-fluoro-carbocyclic nucleosides:: Synthesis, anti-HIV activity and mechanism of resistance
    Wang, Jianing
    Jin, Yunho
    Rapp, Kimberly L.
    Schinazi, Raymond F.
    Chu, Chung K.
    JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (08) : 1828 - 1839
  • [43] 5′-O-ester prodrugs of potent and selective anti-HIV agent-2′,3′-dideoxy-3′-fluoro-2-thiothymidine (S2FLT):: Synthesis and anti-HIV activity
    Miazga, A
    Poopeiko, NE
    Piasek, A
    Siweekar, MA
    Kulikowski, T
    NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, 2003, 22 (5-8): : 805 - 807
  • [44] SYNTHESIS OF 5-DIALKYLAMINOMETHYL-3'-AZIDO AND 3'-FLUORO-2',3'-DIDEOXYURIDINES FOR EVALUATION AS ANTI-HIV AGENTS
    MOTAWIA, MS
    JORGENSEN, PT
    LARNKJAER, A
    PEDERSEN, EB
    NIELSEN, C
    MONATSHEFTE FUR CHEMIE, 1993, 124 (01): : 55 - 64
  • [45] Synthesis, anti-HIV activity, and molecular mechanism of drug resistance of L-2',3′-didehydro-2′,3′-dideoxy-2′-fluoro-4′-thionucleosides
    Choo, H
    Chong, YH
    Choi, YS
    Mathew, J
    Schinazi, RF
    Chu, CK
    JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (03) : 389 - 398
  • [46] Synthesis and evaluation of the anti-hepatitis B virus activity of 4′-Azido-thymidine analogs and 4′-Azido-2′-deoxy-5-methylcytidine analogs: structural insights for the development of a novel anti-HBV agent
    Onitsuka, Kengo
    Tokuda, Ryoh
    Kuwata-Higashi, Nobuyo
    Kumamoto, Hiroki
    Aoki, Manabu
    Amano, Masayuki
    Kohgo, Satoru
    Das, Debananda
    Haraguchi, Kazuhiro
    Mitsuya, Hiroaki
    Imoto, Shuhei
    NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, 2020, 39 (04): : 518 - 529
  • [47] Synthesis and anti-HIV activities of L-β-3′-fluoro-2′,3′-dideoxy-2′,3′-didehydro-4′-thio-nucleosides
    Zhu, W
    Schinazi, RF
    Chu, CK
    ANTIVIRAL RESEARCH, 2003, 57 (03) : A45 - A45
  • [48] INTERACTION OF THE 5'-PHOSPHATES OF THE ANTI-HIV AGENTS, 3'-AZIDO-3'-DEOXYTHYMIDINE AND 3'-AZIDO-2',3'-DIDEOXYURIDINE, WITH THYMIDYLATE SYNTHASE
    DZIK, JM
    BRETNER, M
    KULIKOWSKI, T
    CIESLA, J
    CIESLA, JM
    RODE, W
    SHUGAR, D
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988, 155 (03) : 1418 - 1423
  • [49] 5-HALOGENO-3'-FLUORO-2',3'-DIDEOXYURIDINES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) - POTENT AND SELECTIVE ANTI-HIV ACTIVITY OF 3'-FLUORO-2',3'-DIDEOXY-5-CHLOROURIDINE
    BALZARINI, J
    VANAERSCHOT, A
    PAUWELS, R
    BABA, M
    SCHOLS, D
    HERDEWIJN, P
    DECLERCQ, E
    MOLECULAR PHARMACOLOGY, 1989, 35 (05) : 571 - 577
  • [50] 5-Iodo-2-arylalkylthio-6-aryl pyrimidin-4(3H)-ones as non-nucleoside anti-HBV agents
    Zhang, Yu
    Sun, Xuefeng
    Fan, Ningning
    Zhao, Jianxiong
    Tu, Jing
    Chen, Xiangmei
    Liu, Junyi
    Wang, Xiaowei
    MEDCHEMCOMM, 2015, 6 (08) : 1438 - 1443