基于gaba受体的药物设计

基于GABA受体的药物设计巨修练武汉工程大学GABA(g-aminobutyricacid)OOHNH2ModelofGABAReceptorCl-ModelofCl-ChannelClClClClClClOOSOClClClClClClOOR4R3R6R5R2R7R1lindanea-endosulfanDTDPolychloratedCyclanesOOOHMeOOOOMeOOOOOOOHOOOHOOOpicrotoxininpicrodendrin-QtutiPicrodendrinHomologuesNNClClCF3NH2SOCF3CNSNOONNNOOfipronilLY219048U-93631PhenylpyrazolesOPOOSOOOOPOBrOTBPSEBOBdioxaphosphorinaneTrioxabicyclooctanesOPOR1OOOOR1OR2SSR1R2OR2R1OButylbenzoatesModificationofGABAAntagonistsOOOH3H3[3H]EBOBOOCOOHInhibitionof[3H]EBOBBindingLC50rat=1.41mM,LC50fly=2.90mMOPOOSOPOOSR4R3BicyclicGABAAntagonistsOPOOSNematocidalActivityLD50=24.7mMOPOOSOPOOSLC50rat/LC50housefly=2360nM/45nM=52(invitro）Compound15LD50housefly=0.04mg/fly（invivo）OPOOSABCPresumptionofBindingSitesABCOOOPresumptionofBindingSitesEBOBR2OOR1ABCDPossibleInteractionofGABAAntagonistswithTheirBindingSitesClClONNOF3CCompound14LowestEnergyConformationofCompound14AlignmentofTheTrainingSetPharmacophoreMapofHouseflyGABAReceptorPharmacophoreMapofRatGABAReceptorHouseflyRatComparisonofHouseflyandRatGABAReceptorsGABAreceptorisoneoftheimportanttargetfordevelopinginsecticides.Electrophysiological,biochemical,andpharmacologicalstudieshaveindicatedthatanumberofdifferencesexistbetweeninsectandvertebrateGABAreceptors.Exploringsuchdifferencesby3DQSARmaydevelopsaferinsecticide.Summary欢迎合作，共同发展。本实验室可提供SYBYL6.92软件包