AZT-5′-(p-bromophenyl methoxyalaninyl phosphate) as a potent and non-toxic anti-human immunodeficiency virus agent

被引：6

作者：

Jan, ST

Zhu, Z

Tai, HL

Shih, MJ

Venkatachalam, TK

Uckun, FM ^{[1
]}

机构：

[1] Hughes Inst, Drug Discovery Program, Roseville, MN 55113 USA

[2] Hughes Inst, Dept Chem, Roseville, MN 55113 USA

[3] Hughes Inst, Dept Virol, Roseville, MN 55113 USA

[4] Hughes Inst, Dept Mol Pharmacol, Roseville, MN 55113 USA

来源：

ANTIVIRAL CHEMISTRY & CHEMOTHERAPY | 1999年 / 10卷 / 01期

关键词：

AZT derivatives; HIV; thymidine kinase-deficient T cells;

D O I：

10.1177/095632029901000106

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The potency and selectivity index of the AZT-phenyl phosphate derivatives in thymidine kinase (TK)-deficient T cells were substantially enhanced by introducing a single para-bromo substituent in the phenyl moiety. AZT-5'-(p-bromophenyl methoxyalaninyl phosphate) was 43-fold more potent than AZT-5'-(phenyl methoxyalaninyl phosphate) and was fivefold more potent than AZT in inhibiting human immunodeficiency virus (HIV) replication in TK-deficient CEM cells.

引用

收藏

页码：47 / 52

页数：6

相关论文

共 15 条

[1]

BALZARINI J, 1989, J BIOL CHEM, V264, P6127

[2]

CHU CK, 1989, Patent No. 4841039

[3] ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ACTIVITY OF AN ANTI-CD4 IMMUNOCONJUGATE CONTAINING POKEWEED ANTIVIRAL PROTEIN [J].

ERICE, A ;

BALFOUR, HH ;

MYERS, DE ;

LESKE, VL ;

SANNERUD, KJ ;

KUEBELBECK, V ;

IRVIN, JD ;

UCKUN, FM .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1993, 37 (04) :835-838

[4] PHOSPHORYLATION OF 3'-AZIDO-3'-DEOXYTHYMIDINE AND SELECTIVE INTERACTION OF THE 5'-TRIPHOSPHATE WITH HUMAN-IMMUNODEFICIENCY-VIRUS REVERSE-TRANSCRIPTASE [J].

FURMAN, PA ;

FYFE, JA ;

STCLAIR, MH ;

WEINHOLD, K ;

RIDEOUT, JL ;

FREEMAN, GA ;

LEHRMAN, SN ;

BOLOGNESI, DP ;

BRODER, S ;

MITSUYA, H ;

BARRY, DW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (21) :8333-8337

[5]

HAO Z, 1988, MOL PHARMACOL, V34, P431

[6] ARYL PHOSPHATE DERIVATIVES OF AZT RETAIN ACTIVITY AGAINST HIV-1 IN CELL-LINES WHICH ARE RESISTANT TO THE ACTION OF AZT [J].

MCGUIGAN, C ;

PATHIRANA, RN ;

MAHMOOD, N ;

DEVINE, KG ;

HAY, AJ .

ANTIVIRAL RESEARCH, 1992, 17 (04) :311-321

[7] Phosphoramidate derivatives of d4T with improved anti-HIV efficacy retain full activity in thymidine kinase-deficient cells [J].

McGuigan, C ;

Cahard, D ;

Sheeka, HM ;

DeClercq, E ;

Balzarini, J .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1996, 6 (10) :1183-1186

[8] INTRACELLULAR DELIVERY OF BIOACTIVE AZT NUCLEOTIDES BY ARYL PHOSPHATE DERIVATIVES OF AZT [J].

MCGUIGAN, C ;

PATHIRANA, RN ;

BALZARINI, J ;

DECLERCQ, E .

JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (08) :1048-1052

[9] Aryl phosphoramidate derivatives of d4T have improved anti-HIV efficacy in tissue culture and may act by the generation of a novel intracellular metabolite [J].

McGuigan, C ;

Cahard, D ;

Sheeka, HM ;

DeClercq, E ;

Balzarini, J .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (08) :1748-1753

[10] Probing the mechanism of action and decomposition of amino acid phosphomonoester amidates of antiviral nucleoside prodrugs [J].

McIntee, EJ ;

Remmel, RP ;

Schinazi, RF ;

Abraham, TW ;

Wagner, CR .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (21) :3323-3331