NEW PHOSPHONATE ANALOGS OF 3'-THIA-2',3'-DIDEOXYCYTIDINE (BCH-189) - SYNTHESIS AND ANTI-HIV EVALUATION

被引：13

作者：

KRAUS, JL

机构：

[1] Lahoratnire de Chimie Biomolèculaire, Faculté des Sciences de Luminy, Universite d'Aix-Marseille II, 13288

来源：

NUCLEOSIDES & NUCLEOTIDES | 1993年 / 12卷 / 02期

关键词：

D O I：

10.1080/07328319308021202

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：

New phosphonate analogues of 3'-thia-2',3'-dideoxycytidine (BCH-189) were synthesized in 5 steps via cyclocondensation of 2-mercaptoacetaldehyde di[2-methoxyethyl]acetal with 3-diethylphosphonopropionaldehyde as a key step, followed by a Lewis acid catalyst addition of the appropriate nucleic base. Anti-HIV evaluation of these analogues showed that the alpha-form 3b of 3'-thia-2',3'-dideoxycytidine-4'-ethylene phosphonic acid was inactive while the beta-form 3a was found to be less potent than the parent compound (BCH-189), showing that the replacement of the oxygen in position 5' by a methylene group in the monophosphorylated intermediate diminishes the antiviral activity.

引用

页码：157 / 162

页数：6

共 18 条

[1]

BACH MC, 1989, NEW ENGL J MED, V320, P594

[2]

BEACH W, 1992, J ORG CHEM, V57, P2217

[3]

BELLEAU B, 1989, 5TH P INT C AIDS MON

[4]

BELLEAU B, 1990, Patent No. 3013357

[5] A SIMPLE AND CONVENIENT METHOD FOR THE SELECTIVE N-ACYLATIONS OF CYTOSINE NUCLEOSIDES [J].

BHAT, V ;

UGARKAR, BG ;

SAYEED, VA ;

GRIMM, K ;

KOSORA, N ;

DOMENICO, PA ;

STOCKER, E .

NUCLEOSIDES & NUCLEOTIDES, 1989, 8 (02) :179-183

[6] INSITU COMPLEXATION DIRECTS THE STEREOCHEMISTRY OF N-GLYCOSYLATION IN THE SYNTHESIS OF OXATHIOLANYL AND DIOXOLANYL NUCLEOSIDE ANALOGS [J].

CHOI, WB ;

WILSON, LJ ;

YEOLA, S ;

LIOTTA, DC ;

SCHINAZI, RF .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1991, 113 (24) :9377-9379

[7]

DOURNON E, 1988, LANCET, V2, P1297

[8]

FAURY P, 1992, IN PRESS NUCLEOSIDES

[9] 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

[10] MERCAPTO-ACETALDEHYD UND DIOXY-1.4-DITHIAN [J].

HESSE, G ;

JORDER, I .

CHEMISCHE BERICHTE-RECUEIL, 1952, 85 (9-10) :924-932

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