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 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 (Ki 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.
Original language | English |
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Pages (from-to) | 676-691 |
Number of pages | 16 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 14 |
Issue number | 3 |
DOIs | |
Publication status | Published - Feb 1 2006 |
Keywords
- Molecular modelling
- Opioid receptors affinities and selectivities
- Synthesis of 3,6-diazabicyclo[3.1.1]heptanes
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Organic Chemistry
- Drug Discovery
- Pharmaceutical Science