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

1,4-Benzodioxane, an evergreen, versatile scaffold in medicinal chemistry: A review of its recent applications in drug design

“…7). 101 Obtained according to this approach, the compound with structure 16 (R = Me, Ar = 3-benzothiophene) shows very high 5-HT1A affinity (Ki 1.6 nM), with > 50 fold selectivity over 1-AR, potent 5-HT1A antagonism (IC50 10-20 nM) and no 5-HT-T affinity.…”

Catalytic Asymmetric Nucleophilic Addition of 3-Vinyl Indoles to Imines

“…If so, this transformation will give a concise way leading to the indolyl substituted allylic amines. Many compounds bearing 3-indolyl allylic amine skeletons have been reported with good biological activities, such as 5-HT2A receptors, selective serotonin reuptake inhibitors, and 5-HT1A antagonists . As expected, in the promotion of 10 mol % phosphoric acid ( R )- 3a , the desired product 4a was obtained in moderate yield; however, there was no enantioselective discrimination observed (Table , entry 1).…”

Structure−Activity Relationships for a Novel Series of Dopamine D2-like Receptor Ligands Based on N-Substituted 3-Aryl-8-azabicyclo[3.2.1]octan-3-ol

“…Reduction of this unreacted tropinone with NaBH 4 in the crude product was essential because of its coelution with pure target product during chromatography. The stereoselectivity of this reaction can be attributed to the sterically hindered nature of the bottom-face of the carbonyl group of 13 and 14 toward nucleophilic attack; thus, only endo -3-phenyltropines were produced. ,, Removal of the ethyl carbamate protecting group of 15 − 21 was nontrivial, as reaction with 50% KOH(aq), EtOH, and hydrazine was required for complete deprotection and production of 23 − 29 . Since the 4-methylthiophenyl group of 22 was not stable under these harsh conditions, the tert -butyl carbamate analogues were developed.…”