RESUMEN
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.
Asunto(s)
Animales , Cricetinae , Células CHO , Cricetulus , Diseño de Fármacos , Vectores Genéticos , Estructura Molecular , Oxazinas , Química , Farmacología , Piperazinas , Química , Farmacología , Plásmidos , Unión Proteica , Receptor de Serotonina 5-HT1A , Genética , Metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Genética , Metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina , Metabolismo , Relación Estructura-Actividad , TransfecciónRESUMEN
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.