SYNTHESIS AND ANTIVIRAL ACTIVITY OF NEW CARBONYLPHOSPHONATE 2',3'-DIDEOXY-3'-THIACYTIDINE CONJUGATES

被引：4
|
作者：
CHARVET, AS
TURIN, F
FAURY, P
HANTZ, O
CAMPLO, M
MOURIER, N
BERTHILLON, P
GRACIET, JC
CHERMANN, JC
TREPO, C
KRAUS, JL
机构：
[1] FAC SCI LUMINY,CHIM BIOMOLEC LAB,F-13288 MARSEILLE 9,FRANCE
[2] INSERM,U322,UNITE RETROVIRUS & MALAD ASSOCIEES,F-13273 MARSEILLE 9,FRANCE
[3] INSERM,U271,F-69424 LYON 3,FRANCE
来源：
ANTIVIRAL RESEARCH | 1994年 / 25卷 / 02期
关键词：
2'; 3'-DIDEOXY-3'-THIACYTIDINE; 3'-DIDEOXY-3'-THIACYTIDINE PHOSPHONOFORMIC CONJUGATES; HIV-1; DHBV;
D O I：
10.1016/0166-3542(94)90104-X
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
The synthesis of new potential PFA-BCH-189 conjugate analogues is described and their molecular structure clearly identified through NMR and mass spectra techniques. The anti-HIV-1 activity was determined according to the inhibition of syncytium formation in MT-4 cells, while the anti-HBV activity was determined in infected duck hepatocytes. Both antiviral activities of the PFA-BCH-189 conjugates were much lower than those of the parent BCH-189 (2',3'-dideoxy-3'-thiacytidine) (1). Whereas a prodrug effect, following cleavage and release of the free BCH-189 and PFA, cannot be ruled out, poor cellular permeation of the drug seems to be the most likely reason for the reduced activities against HIV and DHBV. The presence of the PFA moiety appears to be detrimental for both the anti-HIV and anti-DHBV activity of PFA-BCH-189 cases.
引用
收藏
页码：161 / 168
页数：8
相关论文
共 50 条
  • [31] Synthesis and HIV inhibition activity of 2',3'-dideoxy-3'-C-hydroxymethyl nucleosides
    LeeRuff, E
    Ostrowski, M
    Ladha, A
    Stynes, DV
    Vernik, I
    Jiang, JL
    Wan, WQ
    Ding, SF
    Joshi, S
    JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (26) : 5276 - 5280
  • [32] Theoretical study on the hydrolysis mechanism of N,N-dimethyl-N′-(2′,3′-dideoxy-3′-thiacytidine)formamidine
    ZHANG Chang1 & XUE Ying2? 1 College of Chemistry and Environment Protection Engineering
    2 College of Chemistry
    Science China Chemistry, 2008, (10) : 911 - 917
  • [33] Theoretical study on the hydrolysis mechanism of N,N-dimethyl-N′-(2′,3′-dideoxy-3′-thiacytidine)formamidine
    Chang Zhang
    Ying Xue
    Science in China Series B: Chemistry, 2008, 51 : 911 - 917
  • [34] INVITRO TOXICITY OF 2',3'-DIDEOXY-3'-THIACYTIDINE (BCH189/3TC), A NEW SYNTHETIC ANTI-HIV-1 NUCLEOSIDE
    LISIGNOLI, G
    FACCHINI, A
    CATTINI, L
    MONACO, MCG
    DEGRASSI, A
    MARIANI, E
    ANTIVIRAL CHEMISTRY & CHEMOTHERAPY, 1992, 3 (05): : 299 - 303
  • [35] CONVERGENT SYNTHESIS OF 2',3'-DIDEOXY-3'-METHYLTHIO AND 2',3'-DIDEOXY-3'-MERCAPTO NUCLEOSIDES AND THEIR DISULFIDE ANALOGS - POTENTIAL ANTI-HIV AGENTS
    DUEHOLM, KL
    ALY, YL
    JORGENSEN, PT
    ELBARBARY, AA
    PEDERSEN, EB
    NIELSEN, C
    MONATSHEFTE FUR CHEMIE, 1993, 124 (01): : 37 - 53
  • [36] Synthesis and antiviral evaluation of α-D-2′,3′-didehydro-2′,3′-dideoxy-3′-C-hydroxymethyl nucleosides
    Yamada, Kohei
    Hayakawa, Hiroyuki
    Sakata, Shinji
    Ashida, Noriyuki
    Yoshimura, Yuichi
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (20) : 6013 - 6016
  • [37] Mutations at codon 184 in simian immunodeficiency virus reverse transcriptase confer resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine
    Cherry, E
    Slater, M
    Salomon, H
    Rud, E
    Wainberg, MA
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (12) : 2763 - 2765
  • [38] Theoretical study on the hydrolysis mechanism of N,N-dimethyl-N′-(2′,3′-dideoxy-3′-thiacytidine)-formamidine
    Zhang Chang
    Xue Ying
    SCIENCE IN CHINA SERIES B-CHEMISTRY, 2008, 51 (10): : 911 - 917
  • [39] Synthesis of 2′,3′-dideoxy-3′,3′-difluoro and 2′,3′-dideoxy-2′,2′-difluoropyranosyl nucleosides analogues of gemcitabine
    Fernández, R
    Castillón, S
    TETRAHEDRON, 1999, 55 (28) : 8497 - 8508
  • [40] SYNTHESIS OF 3'-CYANO-2',3'-DIDEOXYADENOSINE AND 2',3'-DIDEOXY-3'-FORMYLADENOSINE
    YU, D
    DALARCAO, M
    JOURNAL OF ORGANIC CHEMISTRY, 1989, 54 (13): : 3240 - 3242
12345