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

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 μ-, δ- and κ-receptors were evaluated. The results of the current study revealed a...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2006-02, Vol.14 (3), p.676-691
Main Authors: Loriga, Giovanni, Manca, Ilaria, Murineddu, Gabriele, Chelucci, Giorgio, Villa, Stefania, Gessi, Stefania, Toma, Lucio, Cignarella, Giorgio, Pinna, Gerard A.
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Language:English
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Summary: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 μ-, δ- and κ-receptors were evaluated. The results of the current study revealed a number of compounds ( 3Bb, 3Bg and 3Bh) having a high affinity for μ ( K i at μ-receptors ranging from 2.7 to 7.9 nM) versus δ ( K i at δ-receptors >2000 nM) and versus κ ( K i at κ-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 μ-receptor in very different ways.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2005.09.045