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

Abstract 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 α 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 α 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 α 1 and 5-HT-T.