HYDRAZIDE INHIBITORS OF HIV-1 INTEGRASE
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专利名称：HYDRAZIDE INHIBITORS OF HIV-1
INTEGRASE
发明人：NEAMATI, NOURI,POMMIER, YVES,LIN, ZHAIWEI,BURKE, TERRENCE
申请号：US0006361
申请日：20000310
公开号：WO0053577A9
公开日：
20010920
专利内容由知识产权出版社提供
摘要：The design, synthesis and antiviral activity of novel mercaptosalicylhydrazides are disclosed, which inhibit human immunodeficiency virus type-1 integrase (HIV-1 IN), an essential enzyme for effective viral replication. Examples of the compounds are N,N'-
bis(2-mercaptobenzoyl)hydrazide, N,N'-bis(2,2'-dithiosalicyl)hydrazide, and N,N'-bis(2-mercaptobenzyl)-2,2'-dithiosalicylhydrazide. These compounds are effective against the integrase catalytic core domain, inhibit integrase binding to HIV LTR DNA, and inhibit integrase in preassmbled integrase-DNA complexes. The disclosed mercaptosalicylhydrazides are 300 fold less cytotoxic than other known salicylhydrazides, and exhibit antiviral activity. They are also active in Mg<+2>-based assays, while integrase inhibition by salicylhydrazides is strictly Mn<+2>-dependent. The mercaptosalicylhydrazides have no detectable effect on other retroviral targets, including reverse transcriptase, protease, and virus attachment, and exhibit no detectable activity against human topoisomerase I at concentrations that effectively inhibited integrase. The mercaptosalicylhydrazides of the invention are therefore selective inhibitors of HIV-1 integrase, are useful in therapeutic compositions for the treatment of
HIV disease, and can also be used to find related antiviral drugs.
申请人：THE GOVERNMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES, THE NATIONAL INSTITUTES OF HEALTH,NEAMATI, NOURI,POMMIER, YVES,LIN, ZHAIWEI,BURKE, TERRENCE
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