Medetomidine에 유발된 정좌반사소실에 대한 Tricyclic Isoxazole 유도체들의 항우울성에 관한 3D-QSAR 분석

3D-QSAR Analysis on Antidepressant Activity of Tricyclic Isoxazole Analogues against Medetomidine-induced Loss of Righting

To search the minimum structural requirement of tricyclic isoxazole analogues (1~30) as new class potent antidepressant, thee-dimensional quanti- tative-structure relationship (3D-QSAR) models between substituents (R1~R5) of tricyclic isoxazoles and their antidepressant activity against medetomidine-induced loss of righting were performed and discussed quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indies analysis (CoMSIA) methods. The correlativity and predictability (r2=0.484 and q2=0.947) of CoMSIA-2 model were higher than those of the rest models. The inhibitory activity against medetomidine-induced loss of righting was dependent on electrostatic field (43.4%), hydrophobic field (35.3%), and steric field (21.2%) of tricyclic isoxazoles. From the CoMSIA-2 contour maps, it is predicted that the antidepressant activity of potent antidepressants against medetomidine-induced loss of righting will be able to increase by the substituents (R1~R5) which were in accord with CoMSIA field.