SYNTHESIS, ANTIRETROVIRUS EFFECTS, AND PHOSPHORYLATION KINETICS OF 3'-ISOCYANO-3'-DEOXYTHYMIDINE AND 3'-ISOCYANO-2',3'-DIDEOXYURIDINE

被引:26
作者
HIEBL, J
ZBIRAL, E
BALZARINI, J
DECLERCQ, E
机构
[1] UNIV VIENNA,INST ORGAN CHEM,WAHRINGERSTR 38,A-1090 VIENNA,AUSTRIA
[2] CATHOLIC UNIV LEUVEN,REGA INST MED RES,B-3000 LOUVAIN,BELGIUM
关键词
D O I
10.1021/jm00164a059
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The silylated AzddThd 5 and AzddUrd 6 prepared from 2,3'-anhydronucleoside derivatives 3 and 4 were transformed to formamides 7 and 8 by using the sequence RN3→ RN=P(C6H5)→ RNHCHO. Formamides 7 and 8 were dehydrated to the protected 3'-isocyano derivatives 9 and 10; deblocking gave 11 and 12. Neither 3'-isocyano-3'-deoxythymidine (11) nor 3'-isocyano-2',3'-dideoxyuridine (12) showed anti-HIV activity at noncytotoxic concentrations. ddThd derivative 11 was considerably more toxic to MT-4 cells than ddUrd derivative 12; it also had a much greater affinity (K)ifor MT-4 cell dThd kinase than ddUrd derivative 12. Both compounds appear to be linear mixed-type inhibitors of MT-4 cell dThd kinase. © 1990, American Chemical Society. All rights reserved.
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页码:845 / 848
页数:4
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