The pharmacophore models of diketo acid derivatives integrase inhibitors have established through camparing the structure,activity and side effects of six diketo acid derivatives which have been approved to enter the second phase of clinical trial.6-carbonyl-5-hydroxy-4-oxo-l,4-dihydroquinoline-3-carboxylic acid compounds based on this model have designed as a novel integrase inhibitor,which are characterized by the presence of four electron donor groups close to each other in the skeleton,thus have more strong adhesion with the diatomic metallic ions in integrase catalytic center.In addition,introducing a benzyl group at 6-position chain at quinoline can form hydrophobic interaction with integrase.These compounds are novel potential integrase inhibitors with better conjugation to integrase.These compounds were obtained through Gould-Jacobs reaction,hydrolysis and replacement.