NUCLEOSIDES .158. FLUORINATED SUGAR ANALOGS OF POTENTIAL ANTI-HIV-1 NUCLEOSIDES

被引：55

作者：

HUANG, JT ^{[1
]}

CHEN, LC

WANG, L

KIM, MH

WARSHAW, JA

ARMSTRONG, D

ZHU, QY

CHOU, TC

WATANABE, KA

MATULICADAMIC, J

SU, TL

FOX, JJ

POLSKY, B

BARON, PA

GOLD, JWM

HARDY, WD

ZUCKERMAN, E

机构：

[1] CORNELL UNIV, GRAD SCH MED SCI, MEM SLOAN KETTERING CANC CTR, SLOAN KETTERING INST CANC RES, NEW YORK, NY 10021 USA

[2] CORNELL UNIV, GRAD SCH MED SCI, MEM SLOAN KETTERING CANC CTR, SLOAN KETTERING INST CANC RES, NEW YORK, NY 10021 USA

[3] CORNELL UNIV, GRAD SCH MED SCI, MEM SLOAN KETTERING CANC CTR, SLOAN KETTERING INST CANC RES, NEW YORK, NY 10021 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 05期

关键词：

D O I：

10.1021/jm00109a017

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In order to obtain agents with therapeutic indices superior to those of AZT, FLT, or D4T, several analogues of anti-HIV-1 nucleosides were synthesized. These include 2',3'-dideoxy-2',3'-difluoro-5-methyluridine (13), its arabino analogue 19, arabino-5-methylcytosine analogue 21, 3'-deoxy-2',3'-didehydro-2'-fluorothymidine (25), 3'-azido-2',3'-dideoxy-2'-fluoro-5-methyluridine (29), 2'-azido-3'-fluoro-2',3'-dideoxy-5-methyluridine (31), and 2',3'-dideoxy-2'-fluoro-5-methyluridine (37). These new nucleosides were screened for their activity against HIV and feline TLV in vitro. None of the compounds showed significant activity. It is interesting to note that such a small modification in the sugar moiety of active anti-HIV nucleosides (i.e., displacement of hydrogen by fluorine) almost completely inactivate the agents.

引用

页码：1640 / 1646

页数：7

共 34 条

[1] REACTIONS OF RELEVANCE TO CHEMISTRY OF AMINOGLYCOSIDE ANTIBIOTICS .7. CONVERSION OF THIOCARBONATES INTO DEOXY-SUGARS [J].

BARTON, DHR ;

SUBRAMANIAN, R .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1977, (15) :1718-1723

[2] NEW METHOD FOR DEOXYGENATION OF SECONDARY ALCOHOLS [J].

BARTON, DHR ;

MCCOMBIE, SW .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1975, (16) :1574-1585

[3] REACTION OF METHYL 2,3-ANHYDRO-BETA-D-LYXOFURANOSIDE WITH SODIUM BENZYL MERCAPTIDE [J].

CASINI, G ;

GOODMAN, L .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1964, 86 (07) :1427-&

[4] NUCLEOSIDES .18. SYNTHESIS OF 2]-FLUOROTHYMIDINE 2]-FLUORODEOXYURIDINE + OTHER 2]-HALOGENO-2]-DEOXY NUCLEOSIDES [J].

CODINGTON, JF ;

FOX, JJ ;

DOERR, IL .

JOURNAL OF ORGANIC CHEMISTRY, 1964, 29 (03) :558-&

[5] NUCLEOSIDES OF FLUORO SUGARS .6. SYNTHESIS AND REACTIVITY OF 3'-FLUORO-3'-DESOXYTHYMIDINE AND 3'-CHLORO-3'-DESOXYTHYMIDINE [J].

ETZOLD, G ;

HINTSCHE, R ;

KOWOLLIK, G ;

LANGEN, P .

TETRAHEDRON, 1971, 27 (12) :2463-&

[6] NUCLEOSIDES .16. FURTHER STUDIES OF ANHYDRONUCLEOSIDES [J].

FOX, JJ ;

MILLER, NC .

JOURNAL OF ORGANIC CHEMISTRY, 1963, 28 (04) :936-&

[7] HORIZONTAL TRANSMISSION OF FELINE LEUKEMIA-VIRUS [J].

HARDY, WD ;

HESS, PW ;

ESSEX, M ;

COTTER, S ;

OLD, LJ .

NATURE, 1973, 244 (5414) :266-269

[8]

HARDY WD, 1987, 11TH S INT ASS COMP

[9] ENHANCED INVITRO INHIBITION OF HIV-1 REPLICATION BY 3'-FLUORO-3'-DEOXYTHYMIDINE COMPARED TO SEVERAL OTHER NUCLEOSIDE ANALOGS [J].

HARTMANN, H ;

VOGT, MW ;

DURNO, AG ;

HIRSCH, MS ;

HUNSMANN, G ;

ECKSTEIN, F .

AIDS RESEARCH AND HUMAN RETROVIRUSES, 1988, 4 (06) :457-466

[10] 3'-SUBSTITUTED 2',3'-DIDEOXYNUCLEOSIDE ANALOGS AS POTENTIAL ANTI-HIV (HTLV-III/LAV) AGENTS [J].

HERDEWIJN, P ;

BALZARINI, J ;

DECLERCQ, E ;

PAUWELS, R ;

BABA, M ;

BRODER, S ;

VANDERHAEGHE, H .

JOURNAL OF MEDICINAL CHEMISTRY, 1987, 30 (08) :1270-1278

← 1 2 3 4 →