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 mu-, delta- and K-receptors were evaluated. Several compounds (1e,i.j 2d,e,f,g,j) exhibited a p-affinity in the low nanomolar range with moderate or negligible affinity towards delta- and kappa-receptors. The representative term N-9-(3,3-diphonylprop-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.
N-3(9)-arylpropenyl-N-9(3)-propionyl-3,9-diazabicyclo[3.3.1]nonanes as μ-opioid receptor agonists. Effects on μ-affinity of arylalkenyl chain modifications / Pinna, Gerard Aime; Cignarella, G.; Loriga, G.; Murineddu, Gabriele; Mussinu, J. M.; Ruiu, S.; Fadda, P.; Fratta, W.. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 10:6(2002), pp. 1929-1937. [10.1016/S0968-0896(01)00436-9]
N-3(9)-arylpropenyl-N-9(3)-propionyl-3,9-diazabicyclo[3.3.1]nonanes as μ-opioid receptor agonists. Effects on μ-affinity of arylalkenyl chain modifications
PINNA, Gerard Aime;MURINEDDU, Gabriele;
2002-01-01
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 mu-, delta- and K-receptors were evaluated. Several compounds (1e,i.j 2d,e,f,g,j) exhibited a p-affinity in the low nanomolar range with moderate or negligible affinity towards delta- and kappa-receptors. The representative term N-9-(3,3-diphonylprop-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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
