Abstract

Two series of N-3-arylpropenyl-N-9-propionyl-3,9-diazabicyclo[3.3.1]nonanes (1b-j) and of the reverted N-3-propionyl-N-9-arylpropenyl isomers (2b-j) as analogues of the previously reported analgesic N-3(9)-cinnamyl-N-9(3)-propionyl-3,9-diazabicyclo[3.3.1]nonanes (DBN) (1a, 2a) were synthesised and their affinity and selectivity towards opioid µ-, δ- and k-receptors were evaluated. Several compounds (1e,i,j-2d,e,f,g,j) exhibited a µ-affinity in the low nanomolar range with moderate or negligible affinity towards δ- and k-receptors. The representative term N-9-(3,3-diphenylprop-2-enyl)-N-3-propionyl-DBN (2d) displayed in vivo (mouse) a potent analgesic effect (ED₅₀ 3.88 mg/kg ip) which favourably compared with that of morphine (ED₅₀ 5 mg/kg ip). In addition, 2d produced in mice tolerance after a period twice as long with morphine.

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