SYNTHESIS AND ANTI-HIV ACTIVITY OF SOME HALOALKYL PHOSPHORAMIDATE DERIVATIVES OF 3'-AZIDO-3'-DEOXYTHYMIDINE (AZT) - POTENT ACTIVITY OF THE TRICHLOROETHYL METHOXYALANINYL COMPOUND

被引：64

作者：

MCGUIGAN, C

DEVINE, KG

OCONNOR, TJ

KINCHINGTON, D

机构：

[1] UNIV LONDON UNIV COLL, DEPT CHEM, LONDON WC1E 6BT, ENGLAND

[2] BARTHOLOMEWS HOSP, COLL MED, DEPT VIROL, LONDON, ENGLAND

来源：

ANTIVIRAL RESEARCH | 1991年 / 15卷 / 03期

关键词：

NUCLEOSIDE ANALOG; NUCLEOTIDE ESTER; ANTI-HIV; ANTI-AIDS; PHOSPHORAMIDATE;

D O I：

10.1016/0166-3542(91)90071-X

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Phosphate triester derivatives of AZT have been prepared as membrane-soluble pro-drugs of the bio-active nucleotides, and have been evaluated against HIV-1 in vitro. In particular, the phosphorus centre carries a trichloro- or trifluoroethyl group and a carboxyl-protected, amino-linked amino acid. The compounds are prepared using phosphorochloridate chemistry, and are characterized by a range of techniques. They display potent anti-HIV activity and low host toxicity, but surprisingly this activity does not increase on the introduction of the haloalkyl moiety. The trichloroethyl methoxyalaninyl compound is exceptional: here the activity is enhanced 50-fold by the introduction of the trichloroethyl group.

引用

收藏

页码：255 / 263

页数：9

相关论文

共 20 条

[1] SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME PHOSPHATE TRIESTER DERIVATIVES OF THE ANTI-CANCER DRUG ARAC [J].

COLIN, B ;

JONES, NM ;

MCGUIGAN, C ;

RILEY, PA .

NUCLEIC ACIDS RESEARCH, 1989, 17 (18) :7195-7201

[2]

CURLEY D, 1990, ANTIVIR RES, V14, P345, DOI 10.1016/0166-3542(90)90053-A

[3] MiniReview: Antiviral Targets Series, Number 1 Targets for antiviral chemotherapy: HIV-proteinase [J].

Dunn, B. M. ;

Kay, J. .

ANTIVIRAL CHEMISTRY & CHEMOTHERAPY, 1990, 1 (01) :3-8

[4] SYNTHESIS AND BIOLOGICAL PROPERTIES OF NOVEL PHOSPHOTRIESTERS - A NEW APPROACH TO THE INTRODUCTION OF BIOLOGICALLY-ACTIVE NUCLEOTIDES INTO CELLS [J].

FARROW, SN ;

JONES, AS ;

KUMAR, A ;

WALKER, RT ;

BALZARINI, J ;

DECLERCQ, E .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (05) :1400-1406

[5] INHIBITION OF HERPES-SIMPLEX VIRUS-INDUCED DNA-POLYMERASE ACTIVITY AND VIRAL-DNA REPLICATION BY 9-(2-HYDROXYETHOXYMETHYL)GUANINE AND ITS TRIPHOSPHATE [J].

FURMAN, PA ;

STCLAIR, MH ;

FYFE, JA ;

RIDEOUT, JL ;

KELLER, PM ;

ELION, GB .

JOURNAL OF VIROLOGY, 1979, 32 (01) :72-77

[6] 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

[7] 6-SUBSTITUTED AND 1-SUBSTITUTED MANNOSYL PHOSPHOTRIESTERS AS LIPOPHILIC MACROPHAGE-TARGETED CARRIERS OF ANTIVIRAL NUCLEOSIDES [J].

GOUYETTE, C ;

NEUMANN, JM ;

FAUVE, R ;

HUYNHDINH, T .

TETRAHEDRON LETTERS, 1989, 30 (44) :6019-6022

[8] COMPARISON OF ANTIGEN CAPTURE ASSAYS AGAINST HIV-1 IN EVALUATING ANTIVIRAL COMPOUNDS [J].

KINCHINGTON, D ;

GALPIN, SA ;

OCONNOR, TJ ;

JEFFRIES, DJ ;

WILLIAMSON, JD .

AIDS, 1989, 3 (02) :101-104

[9]

LEIBMAN KC, 1955, J BIOL CHEM, V216, P823

[10]

LICHTENSTEIN J, 1960, J BIOL CHEM, V235, P457