RÉSUMÉ
Compounds with serotonin reuptake inhibition/5-HT(1A) dual activity were used to build 3D pharmacophore model as a training molecules by Discover Studio. Based on the model, 8 novel aryl piperazine benzo[b][1,4] oxazine derivatives were designed and synthesized, and their structures were confirmed by 1H NMR and HR-MS. Biological evaluation illustrated that compounds VI(1) and VI(7) showed potent functional activities at both 5-HT transporter and 5-HT(1A) receptor, which can be used as lead compounds to guide future research of design and synthesis of potent novel compounds.
Sujet(s)
Animaux , Cricetinae , Cellules CHO , Cricetulus , Conception de médicament , Vecteurs génétiques , Structure moléculaire , Oxazines , Chimie , Pharmacologie , Pipérazines , Chimie , Pharmacologie , Plasmides , Liaison aux protéines , Récepteur de la sérotonine de type 5-HT1A , Génétique , Métabolisme , Transporteurs de la sérotonine , Génétique , Métabolisme , Inbiteurs sélectifs de la recapture de la sérotonine , Métabolisme , Relation structure-activité , TransfectionRÉSUMÉ
To explore novel monoamine reuptake inhibitor with antidepressant activity, a series of substituted aryl alkanol piperidine derivatives were designed and synthesized. All of them were new compounds, and their structures were confirmed with 1H NMR and HR-MS. The results showed that compounds 4, 5 and 8 displayed strong 5-HT, NA and DA reuptake inhibiting activities in vitro. Among the tested compounds, 4, 5 and 13 exhibited potent antidepressant activities in the mice forced swimming test. Compounds 4 and 5 have potent antidepressant activities and are worth further development.