1249480-68-9Relevant academic research and scientific papers
Molecular hybridization of 4-azahexacyclo[5.4.1.02,6.0 3,10.05,9.08,11]dodecane-3-ol with sigma (σ) receptor ligands modulates off-target activity and subtype selectivity
Banister, Samuel D.,Moussa, Iman A.,Jorgensen, William T.,Chua, Sook Wern,Kassiou, Michael
, p. 3622 - 3626 (2011)
A series of N-substituted 4-azahexacyclo[5.4.1.02,6.0 3,10.05,9.08,11]dodecan-3-ols incorporating the respective arylalkyl subunits from several known sigma (σ) receptor ligands were synthesized and evaluated for their affinity against σ receptors and dopamine receptors. The hybrid trishomocubane-derived ligands (4-6) showed good selectivity for σ1 and σ2 receptors over multiple dopamine receptors. The molecular hybrid obtained from haloperidol and 4-azahexacyclo[5.4.1.02,6.03,10.0 5,9.08,11]dodecan-3-ol (4, σ1 K i = 27 nM, σ2 Ki = 55 nM) showed reduced affinity for D1-D5 dopamine receptors when compared to haloperidol itself. The compound with the greatest σ1 affinity in the series, benzamide 4 (σ1 Ki = 7.6 nM, σ2 Ki = 225 nM) showed a complete reversal of the subtype selectivity displayed by the highly σ2 selective parent benzamide, RHM-2 (3, σ1 Ki = 10412 nM, σ2 Ki = 13.3 nM).
