Α series of novel 3,6-diazabicyclo[3.1.1]heptane derivatives 4a-f was synthesized and their affinity and selectivity towards α4β2 and α7 nAChR subtypes were evaluated. The results of the current study revealed a number of compounds (4a, 4b and 4c) having a very high affinity for α4β2 (Ki at α4β2 ranging from 0.023 to 0.056 nM) versus α7 nAChR subtypes; among these compounds, the 3-(6-bromopyridin-3-yl)-3,6-diazabicyclo[3.1.1]heptane 4c was found to be the most α7α4β2 selective term in receptor binding assays (α7α4β2 = 1295). Moreover, compound 4d also had high affinity for the α4β2 nAChR subtype (Ki = 1.2 nM) with considerably high selectivity (α7/α4β2 = 23300).
Murineddu, G., Murruzzu, C., Curzu Maria, M., Chelucci, G., Gotti, C., Gaimarri, A., et al. (2008). Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for neuronal nicotinic acetylcholine receptors. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 18(23), 6147-6150 [10.1016/j.bmcl.2008.10.002].
Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for neuronal nicotinic acetylcholine receptors
LEGNANI, LAURA;
2008
Abstract
Α series of novel 3,6-diazabicyclo[3.1.1]heptane derivatives 4a-f was synthesized and their affinity and selectivity towards α4β2 and α7 nAChR subtypes were evaluated. The results of the current study revealed a number of compounds (4a, 4b and 4c) having a very high affinity for α4β2 (Ki at α4β2 ranging from 0.023 to 0.056 nM) versus α7 nAChR subtypes; among these compounds, the 3-(6-bromopyridin-3-yl)-3,6-diazabicyclo[3.1.1]heptane 4c was found to be the most α7α4β2 selective term in receptor binding assays (α7α4β2 = 1295). Moreover, compound 4d also had high affinity for the α4β2 nAChR subtype (Ki = 1.2 nM) with considerably high selectivity (α7/α4β2 = 23300).
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