[Design, synthesis and bioactivity of aryl piperazine benzo[b][1,4]oxazine derivatives].
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.
Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China.
Yong-Yong
YY
Zheng
Peng
P
Xie
Jin
J
Zhang
Jian-Qi
JQ
Li
Lin
L
Guo
Lei-Ping
LP
Yu
Bin
B
Zhou
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D005822:Genetic Vectors; D015394:Molecular Structure; D010078:Oxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010957:Plasmids; D011485:Protein Binding; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection
D010078:Oxazines; D000077489:Piperazine; D010879:Piperazines; D044282:Receptor, Serotonin, 5-HT1A; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors