COSALANE ANALOGS WITH ENHANCED POTENCIES AS INHIBITORS OF HIV-1 PROTEASE AND INTEGRASE

被引：84

作者：

CUSHMAN, M

GOLEBIEWSKI, WM

POMMIER, Y

MAZUMDER, A

REYMEN, D

DECLERCQ, E

GRAHAM, L

RICE, WG

机构：

[1] NCI, DIV CANC TREATMENT, DEV THERAPEUT PROGRAM, MOLEC PHARMACOL LAB, BETHESDA, MD 20892 USA

[2] KATHOLIEKE UNIV LEUVEN, REGA INST MED RES, B-3000 LOUVAIN, BELGIUM

[3] NCI, FREDERICK CANC RES & DEV CTR, PROGRAM RESOURCES INC DYNCORP, ANTIVIRAL DRUG MECHANISMS LAB, FREDERICK, MD 21702 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 38卷 / 03期

关键词：

D O I：

10.1021/jm00003a007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Several new analogues of the novel anti-HIV agent cosalane have been synthesized and evaluated as inhibitors of HIV-1 integrase and protease, HIV-1 replication, HIV-1 and HIV-2 cytopathicity, HIV-1- and HIV-2-mediated syncytium formation, and cytopathicity of a variety of human pathogenic viruses. The congeners displayed enhanced potencies relative to cosalane itself as inhibitors of HIV-1 integrase and protease. The two most potent analogues against HIV-1 integrase displayed IC50 values of 2.2 mu M, while the three most potent compounds against HIV-1 protease had IC50 values in the 0.35-0.39 mu M range. In addition to its activity against HIV-1 and HIV-2 cytopathicity, cosalane inhibited the cytopathic effects of herpes simplex virus-1, herpes simplex virus-2, and human cytomegalovirus at concentrations that were well below the cytotoxic concentrations. Potentially useful antiviral activities were also revealed for some of the new cosalane congeners against influenza virus, Junin virus, and Tacaribe virus.

引用

页码：443 / 452

页数：10

共 63 条

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