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 |
|---|---|
| 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 |
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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
Cite this
Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for the opioid receptors. / Loriga, Giovanni; Manca, Ilaria; Murineddu, Gabriele; Chelucci, Giorgio; Villa, Stefania; Gessi, Stefania; Toma, Lucio; Cignarella, Giorgio; Pinna, Gerard A.
In: Bioorganic and Medicinal Chemistry, Vol. 14, No. 3, 01.02.2006, p. 676-691.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for the opioid receptors
AU - Loriga, Giovanni
AU - Manca, Ilaria
AU - Murineddu, Gabriele
AU - Chelucci, Giorgio
AU - Villa, Stefania
AU - Gessi, Stefania
AU - Toma, Lucio
AU - Cignarella, Giorgio
AU - Pinna, Gerard A.
PY - 2006/2/1
Y1 - 2006/2/1
N2 - 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.
AB - 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.
KW - Molecular modelling
KW - Opioid receptors affinities and selectivities
KW - Synthesis of 3,6-diazabicyclo[3.1.1]heptanes
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UR - http://www.scopus.com/inward/citedby.url?scp=28844505735&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2005.09.045
DO - 10.1016/j.bmc.2005.09.045
M3 - Article
C2 - 16243530
AN - SCOPUS:28844505735
VL - 14
SP - 676
EP - 691
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 3
ER -