Modulation of selective serotonin reuptake inhibitor and 5-HT1A antagonist activity in 8-aza-bicyclo[3.2.1]octane derivatives of 2,3-dihydro-1,4-benzodioxane.
2,3-Dihydro-1,4-benzodioxanes with aryl 8-aza-bicyclo[3.2.1]oct-3-ene attachments 2 produce compounds with potent 5-HT-T affinity, and weak 5-HT(1A) affinity and alpha(1) affinity. This compares with 2,3-dihydro-1,4-benzodioxanes containing 8-aza-bicyclo[3.2.1] octan-3-ol attachments 4 which possess potent 5-HT(1A) affinity, moderate to good selectivity over alpha(1) and little 5-HT-T affinity. A 3-benzothiophene analogue of 4 (30) was synthesized which possesses potent 5-HT(1A) affinity and especially good selectivity over both alpha(1) and 5-HT-T.
Gilbert
Adam M
AM
Chemical and Screening Sciences, Wyeth Research, 401N. Middletown Road, Pearl River, NY 10945, USA. gilbera@wyeth.com
Stack
Gary P
GP
Nilakantan
Ramaswamy
R
Kodah
Jason
J
Tran
Megan
M
Scerni
Rosemary
R
Shi
Xiaojie
X
Smith
Deborah L
DL
Andree
Terrance H
TH
D001643:Bridged Bicyclo Compounds / Q000378:metabolism / Q000494:pharmacology*; D004146:Dioxanes / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D009795:Octanes / Q000378:metabolism / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000494:pharmacology*
D001643:Bridged Bicyclo Compounds; D004146:Dioxanes; D009795:Octanes; D044282:Receptor, Serotonin, 5-HT1A; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors