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Your search keyword '"Cignarella, Giorgio"' showing total 2 results
Start Over Author "Cignarella, Giorgio" Topic bridged bicyclo compounds, heterocyclic
2 results on '"Cignarella, Giorgio"'

1. Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for the opioid receptors.

Author

Loriga G, Manca I, Murineddu G, Chelucci G, Villa S, Gessi S, Toma L, Cignarella G, and Pinna GA

Subjects
Animals, Brain metabolism, Bridged Bicyclo Compounds, Heterocyclic chemistry, In Vitro Techniques, Kinetics, Ligands, Male, Mice, Models, Molecular, Molecular Conformation, Molecular Structure, Receptors, Opioid, delta metabolism, Receptors, Opioid, kappa metabolism, Receptors, Opioid, mu metabolism, Thermodynamics, Bridged Bicyclo Compounds, Heterocyclic chemical synthesis, Bridged Bicyclo Compounds, Heterocyclic metabolism, Receptors, Opioid metabolism
Abstract

In an effort to improve diazabicycloalkane-based opioid receptor ligands, N-3(6)-arylpropenyl-N-6(3)-propionyl-3,6-diazabicyclo[3.1.1]heptanes (3A,Ba-i) were synthesized and their affinity and selectivity towards mu-, delta- and kappa-receptors were evaluated. The results of the current study revealed a number of compounds (3Bb, 3Bg and 3Bh) having a high affinity for mu (Ki at mu-receptors ranging from 2.7 to 7.9 nM) versus delta (Ki at delta-receptors > 2000 nM) and versus kappa (Ki at kappa-receptors > 5000 nM) receptors. Molecular modelling carried out on the pair 3Aa/3Ba and on the 3Bh was consistent with the hypothesis that the two series of compounds 3A and 3B interact with the mu-receptor in very different ways.

Published
2006
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2. N-3(9)-arylpropenyl-N-9(3)-propionyl-3,9-diazabicyclo[3.3.1]nonanes as mu-opioid receptor agonists. Effects on mu-affinity of arylalkenyl chain modifications.

Author

Pinna GA, Cignarella G, Loriga G, Murineddu G, Mussinu JM, Ruiu S, Fadda P, and Fratta W

Subjects
Analgesics, Opioid chemical synthesis, Analgesics, Opioid metabolism, Animals, Brain cytology, Bridged Bicyclo Compounds, Heterocyclic chemical synthesis, Bridged Bicyclo Compounds, Heterocyclic metabolism, Cell Membrane drug effects, Cell Membrane metabolism, Inhibitory Concentration 50, Male, Mice, Molecular Structure, Pain Measurement, Receptors, Opioid, mu metabolism, Structure-Activity Relationship, Substrate Specificity, Analgesics, Opioid chemistry, Analgesics, Opioid pharmacology, Bridged Bicyclo Compounds, Heterocyclic chemistry, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Receptors, Opioid, mu agonists
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 kappa-receptors were evaluated. Several compounds (1e,i,j-2d,e,f,g,j) exhibited a mu-affinity in the low nanomolar range with moderate or negligible affinity towards delta- and kappa-receptors. The representative term N-9-(3,3-diphenylprop-2-enyl)-N-3-propionyl-DBN (2d) displayed in vivo (mouse) a potent analgesic effect (ED(50) 3.88 mg/kg ip) which favourably compared with that of morphine (ED(50) 5 mg/kg ip). In addition, 2d produced in mice tolerance after a period twice as long with morphine.

Published
2002
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