The Design, Synthesis And Activity Study Of Caffeoyl-Benzenesulfonamindes As HIV-1 Integrase Inhibitors

Nowadays almost every stage of life period and related enzymes of HIV have become pharmacal target for anti-HIV drug design.HIV-1 is a retrovirus,whose life cycle depends on the fusion,transcriptase(RT),protease(PI),and integrase(IN). Current drug research mainly focus on reverse transcriptase and reverse transcriptase. The application of highly active anti-retroviral therapy greatly reduces mortality of AIDS.However,the emergence of multidrug resistant,toxicity and side-effect drug itself and drug drug interaction restrict its application.The HIV-1 integrase is an essential enzyme which catalyzes the insertion of the viral DNA into the genome of the host cell.Moreover,there is no known human homologue to integrase and the reactions catalyzed by IN are unique.This allows design of selective inhibitors with little or no side effects,and makes IN as an attractive target for therapeutic intervention.Among the reported HIV-1 integrase inhibitors,polyhydroxylated aromatics represent a promising class of compounds,their structure-function relationship and mechanism of action are relatively clear.They are inhibitors of enzymatic 3'-processing strand transfer.1,5-DCQA that has enterred into clinical research belongs to these compounds.In this paper,we design a series novel compounds using caffeic acid phenethyl ester as lead compound.We keep the caffeoyl as pharmacophore,and to explore the effect of different substituent aryl groups on activity by changing polarity, hydrophobicity and vacuity size of aryl group.All the new compounds are prepared by applying different aromatic acid with different number and substitution position of phenolic hydroxyl groups and different arylamines as raw materials through reactions of acylation,sulfonylation,condensation,hydrolization and so on.The chemical structures of these compounds are identified by IR,MS,and 1H-NMR spectra. Integrase inhibitory activity of some compounds were tested.