Design And Synthesis Of N,N'-Bis(Aromatic Hydrazide) Derivatives For Human Immunodeficiency Virus Integrase Inhibitors

AIDS has spread around almost all countries in the world since a scientist found the first AIDS patient in America. Up to the end of 2004, almost 80 million people infected HIV in the world.Anti-AIDS drugs in clinic can be divided into HIV-1 reverse transcriptase inhibitors and HIV-1 protease inhibitors at present time. More and more doctors used these drugs and viruses developed resistance to drugs. And the patients need new anti-AIDS drugs because therapeutic valence has reduced obviously.HIV-1 integrase is an important enzyme in HIV-1 life cycle (other two important enzymes are reverse transcriptase and protease). Because of the special function of HIV-1 integrase, it has become one of focuses of anti-AIDS drug design.According to the structure of HIV-1 integrase, we design and synthesize 19 N,N' -bis (aromatic hydrazide) derivatives . And 18 compounds are firstly reported. In order to find the best electronic effect and steric effect characteristic structures which bind to HIV-1 integrase , we substitute 4 and 5 position of target compounds by different groups, including methyl, methoxy and chloro so on.In the chemical experiment parts, we refer to internal and international literature. And we fish for and improve on several methods about synthesis way of intermediates and target compounds.We carry out screening of outer anti-virus activity by employing HIV-1 integrase. And we attain HIV-1 integrase by gene recombinant DNA technology .