ACTIVITY OF VARIOUS THIOCARBOXANILIDE DERIVATIVES AGAINST WILD-TYPE AND SEVERAL MUTANT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 STRAINS

被引：37

作者：

BALZARINI, J

BROUWER, WG

FELAUER, EE

DECLERCQ, E

KARLSSON, A

机构：

[1] UNIROYAL CHEM CO LTD,GUELPH,ON N1E 5L7,CANADA

[2] KAROLINSKA INST,S-17177 STOCKHOLM,SWEDEN

来源：

ANTIVIRAL RESEARCH | 1995年 / 27卷 / 03期

关键词：

OXATHIIN CARBOXANILIDE; HIV; RESISTANCE; AIDS;

D O I：

10.1016/0166-3542(95)00006-8

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

A large variety of carboxanilide derivatives in which the original oxathiin moiety present in the prototype compound UC84 was replaced by a non-cyclic lipophilic entity has been evaluated for their inhibitory effect against wild-type human immunodeficiency virus type 1 (HIV-1/IIIB) and several mutant viruses derived thereof (i.e. HIV-1/138-Lys, HIV-1/181-Cys, HIV-1/106-Ala and HIV-1/100-Ile). Isopropoxy was the most favorable substituent resulting in molecules that were markedly inhibitory to the wild-type (EC(50) 0.004-0.04 mu g/ml) as well as the mutant HIV-1 strains (EC(50) 0.06-0.75 mu g/ml). In this respect, they proved superior to several other HIV-1-specific non-nucleoside reverse transcriptase inhibitors (NNRTIs) that are currently the subject of clinical trials. One of the most potent HIV-1 inhibitors among the thiocarboxanilide derivatives, namely UC38, selected for a mutant virus strain in which Lys at position 101 and Gly at position 190 of the reverse transcriptase was replaced by Glu.

引用

页码：219 / 236

页数：18

共 19 条

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