SYNTHESIS OF A DIFLUOROMETHYLENEPHOSPHONATE ANALOG OF AZT-5'-TRIPHOSPHATE AND ITS INHIBITION OF HIV-1 REVERSE-TRANSCRIPTASE

被引：34

作者：

HEBEL, D ^{[1
]}

KIRK, KL ^{[1
]}

KINJO, J ^{[1
]}

KOVACS, T ^{[1
]}

LESIAK, K ^{[1
]}

BALZARINI, J ^{[1
]}

DECLERCQ, E ^{[1
]}

TORRENCE, PF ^{[1
]}

机构：

[1] REGA INST,B-3000 LOUVAIN,BELGIUM

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1991年 / 1卷 / 07期

关键词：

D O I：

10.1016/S0960-894X(01)80472-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Difluoromethylenebisphosphonic acid was prepared by acetyl hypofluorite-mediated fluorination of tetraisopropyl methylenebisphosphonate and ester hydrolysis. Coupling to 3'-azido-3'-deoxythymidine 5'-monophosphate gave the title compound. The difluoromethylenephosphonate was 30-fold less effective than AZT-triphosphate as a competitive inhibitor of HIV-1 reverse transcriptase but 10-fold more effective than the methylenephosphonate analogue.

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页码：357 / 360

页数：4

相关论文

共 13 条

[1] ALPHA,BETA-METHYLENE AND BETA,GAMMA-METHYLENE 5'-PHOSPHONATE DERIVATIVES OF 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE-5'-TRIPHOSPHATE - CORRELATION BETWEEN AFFINITY FOR REVERSE-TRANSCRIPTASE, SUSCEPTIBILITY TO HYDROLYSIS BY PHOSPHODIESTERASES AND ANTI-RETROVIRUS ACTIVITY [J].

BALZARINI, J ;

HERDEWIJN, P ;

PAUWELS, R ;

BRODER, S ;

DECLERCQ, E .

BIOCHEMICAL PHARMACOLOGY, 1988, 37 (12) :2395-2403

[2] ISOPRENOID (PHOSPHINYLMETHYL)PHOSPHONATES AS INHIBITORS OF SQUALENE SYNTHETASE [J].

BILLER, SA ;

FORSTER, C ;

GORDON, EM ;

HARRITY, T ;

SCOTT, WA ;

CIOSEK, CP .

JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (10) :1869-1871

[3]

BLACKBURN GM, 1986, CHEM SCRIPTA, V26, P21

[4] PREPARATION OF F-METHYLENE BIS PHOSPHONATES [J].

BURTON, DJ ;

FLYNN, RM .

JOURNAL OF FLUORINE CHEMISTRY, 1980, 15 (03) :263-266

[5] FLUORINE IN ENZYME CHEMISTRY .2. THE PREPARATION OF DIFLUOROMETHYLENEPHOSPHONATE ANALOGS OF GLYCOLYTIC PHOSPHATES - APPROACHING AN ISOSTERIC AND ISOELECTRONIC PHOSPHATE MIMIC [J].

CHAMBERS, RD ;

JAOUHARI, R ;

OHAGAN, D .

TETRAHEDRON, 1989, 45 (16) :5101-5108

[6] SYNTHESIS OF NUCLEOTIDE 5'-DIPHOSPHATES FROM 5'-O-TOSYL NUCLEOSIDES [J].

DAVISSON, VJ ;

DAVIS, DR ;

DIXIT, VM ;

POULTER, CD .

JOURNAL OF ORGANIC CHEMISTRY, 1987, 52 (09) :1794-1801

[7] TARGETS AND STRATEGIES FOR THE ANTIVIRAL CHEMOTHERAPY OF AIDS [J].

DECLERCQ, E .

TRENDS IN PHARMACOLOGICAL SCIENCES, 1990, 11 (05) :198-205

[8] 9-(DIFLUOROPHOSPHONOALKYL)GUANINES AS A NEW CLASS OF MULTISUBSTRATE ANALOG INHIBITORS OF PURINE NUCLEOSIDE PHOSPHORYLASE [J].

HALAZY, S ;

EHRHARD, A ;

DANZIN, C .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1991, 113 (01) :315-317

[9] MECHANISM OF HIV REVERSE-TRANSCRIPTASE - ENZYME PRIMER INTERACTION AS REVEALED THROUGH STUDIES OF A DNTP ANALOG, 3'-AZIDO-DTTP [J].

KEDAR, PS ;

ABBOTTS, J ;

KOVACS, T ;

LESIAK, K ;

TORRENCE, P ;

WILSON, SH .

BIOCHEMISTRY, 1990, 29 (15) :3603-3611

[10] A NOVEL ELECTROPHILIC FLUORINATION OF ACTIVATED AROMATIC RINGS USING ACETYL HYPOFLUORITE, SUITABLE ALSO FOR INTRODUCING F-18 INTO BENZENE NUCLEI [J].

LERMAN, O ;

TOR, Y ;

HEBEL, D ;

ROZEN, S .

JOURNAL OF ORGANIC CHEMISTRY, 1984, 49 (05) :806-813