Neuronal nicotinic acetylcholine receptors (nAChRs), activated by the endogenous neurotransmitter acetylcholine and the natural alkaloid nicotine, emerged as important target in drug discovery. Among the plethora of different receptor subtypes the most abundant in the CNS are the α4β2and the α7receptors. Since the different nAChRs posses distinctive biophysical, pharmacological and physiological properties, the selective modulation of each subtype represents an intriguing challenge for the development of new drugs for the treatment of different disorders of CNS. In this work we reported optimized methods for the syntheses of novel 3,6-diazabicyclo[3.1.1]heptaneheteroaryl derivates in which the heteroaromatic rings have been modulated by different functionalizations. The changes were made mainly on the pyridine ring in order to investigate the effect of different substitutions on α4β2and α7nAChR affinity and selectivity. By preliminary binding studies, the new synthesized compounds showed high affinity for nAChR subtypes and at the same time some derivatives displayed a noticeable α4β2selectivity. We have designed and synthesized several ligands series for nAChR with a 3,6-diazabicyclo[3.1.1]heptane core linked with aza- or diaza-rings variously substituted. The study allowed the synthesis of derivatives with high affinity and selectivity for nAChRs highlighting as the position of the substituent is a determinant factor for the selectivity on α4β2receptor subtypes.

Sintesi e caratterizzazione biologica di nuovi 3,6-diazabiciclo[3.1.1]eptani quali potenti e selettivi ligandi per i recettori neuronali nicotinici α4β2e α7 / Deligia, Francesco. - (2013 Feb 18).

Sintesi e caratterizzazione biologica di nuovi 3,6-diazabiciclo[3.1.1]eptani quali potenti e selettivi ligandi per i recettori neuronali nicotinici α4β2e α7

DELIGIA, Francesco
2013-02-18

Abstract

Neuronal nicotinic acetylcholine receptors (nAChRs), activated by the endogenous neurotransmitter acetylcholine and the natural alkaloid nicotine, emerged as important target in drug discovery. Among the plethora of different receptor subtypes the most abundant in the CNS are the α4β2and the α7receptors. Since the different nAChRs posses distinctive biophysical, pharmacological and physiological properties, the selective modulation of each subtype represents an intriguing challenge for the development of new drugs for the treatment of different disorders of CNS. In this work we reported optimized methods for the syntheses of novel 3,6-diazabicyclo[3.1.1]heptaneheteroaryl derivates in which the heteroaromatic rings have been modulated by different functionalizations. The changes were made mainly on the pyridine ring in order to investigate the effect of different substitutions on α4β2and α7nAChR affinity and selectivity. By preliminary binding studies, the new synthesized compounds showed high affinity for nAChR subtypes and at the same time some derivatives displayed a noticeable α4β2selectivity. We have designed and synthesized several ligands series for nAChR with a 3,6-diazabicyclo[3.1.1]heptane core linked with aza- or diaza-rings variously substituted. The study allowed the synthesis of derivatives with high affinity and selectivity for nAChRs highlighting as the position of the substituent is a determinant factor for the selectivity on α4β2receptor subtypes.
18-feb-2013
3,6-diazabiciclo[3.1.1]eptano; nAChR α4β2; nAChR α7
Sintesi e caratterizzazione biologica di nuovi 3,6-diazabiciclo[3.1.1]eptani quali potenti e selettivi ligandi per i recettori neuronali nicotinici α4β2e α7 / Deligia, Francesco. - (2013 Feb 18).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/250994
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