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 VI₁ and VI₇ 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.