Integrase　has　become　an　attractive　target　for　the　design　of　anti-HIV　inhibitor　because　it　plays　a　quite　important　role　in　the　process　of　HIV-1　virus　replication.　The　quinoline　ring　derivatives,　which　have　the　similar　pharmacophore　to　..-diketoacids,　are　the　kind　of　integrase　inhibitor　with　highly　antiviral　activity.　A　series　of　quinoline　ring　derivatives　were　analyzed　by　the　Comparative　Molecular　Field　Analysis　(CoMFA),　comparative　molecular　similarity　induces　analysis　(CoMSIA)　and　Topomer　CoMFA　methods.　Firstly,　we　chose　77　compounds　from　former　papers　as　a　dataset,　followed　by　dividing　it　into　the　training　set　and　test　set　randomly.　Then,　we　constructed　predictive　models　of　CoMFA,　CoMSIA　and　Topomer　CoMFA,　respectively.　The　CoMFA　yielded　the　best　cross-validated　model　with　a　q2=0.758,　non-cross-validated　r　2=0.988.　The　CoMSIA　model　yielded　a　q2　=0.701　and　r　2　=0.986　while　the　Topomer　CoMFA　model　has　q2　=0.661　and　r2　=　0.966.　Through　verification,　these　results　suggested　a　strong　predictive　ability　to　the　design　of　novel　highly　active　HIV-1　integrase　inhibitors　for　therapy.　©　2013　Springer-Verlag.