Novel 2-N,N-dimethylaminomethyl-2,3,3a,12b-tetrahydrodibenzo[b,f]furo[2,3-d]oxepin derivatives displaying combined norepinephrine reuptake inhibition and 5-HT2A/2C receptor antagonism.
A novel series of cis-fused 2-N,N-dimethylaminomethyl-2,3,3a,12b-tetrahydrodibenzo[b,f]furo[2,3-d]oxepin derivatives modified at position C-11 was prepared and evaluated for its potential antidepressant/anxiolytic properties. In vitro affinities for the norepinephrine transporter and for 5-HT(2A) and 5-HT(2C) receptors, as well as the ED(50) values obtained in some in vivo assays predictive for antidepressant and anxiolytic potential are reported.
Bartolomé
José M
JM
Johnson & Johnson Pharmaceutical Research & Development, Division of Janssen-Cilag, S.A. Medicinal Chemistry Department, Toledo, Spain. jbartolo@prdes.jnj.com
Alcudia
Ana
A
Andrés
José I
JI
Cid
José M
JM
García
Mercedes
M
Megens
Anton
A
Toledo
Miguel A
MA
Trabanco
Andrés A
AA
D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010082:Oxepins / Q000138:chemical synthesis* / Q000494:pharmacology*; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D027981:Symporters / Q000037:antagonists & inhibitors
C504933:2-N,N-dimethylaminomethyl-2,3,3a,12b-tetrahydrodibenzo(b,f)furo(2,3-d)oxepin; D001572:Benzofurans; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010082:Oxepins; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D027981:Symporters; D009638:Norepinephrine