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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Published in: | Bioorganic & medicinal chemistry 2006-02, Vol.14 (3), p.676-691 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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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. |
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ISSN: | 0968-0896 1464-3391 |
DOI: | 10.1016/j.bmc.2005.09.045 |