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