Rigid analogs of DMPP as probes for the nicotinic receptors

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• 作者：Guandalini ; Luca ; Martini ; Elisabetta ; Martelli ; Cecilia ; Romanelli ; M. Novella ; Varani ; Katia
• 关键词：Nicotinic receptor ligands ; Structure??????activity relationships ; DMPP analogs ; Frozen-analog approach
• 刊名：Il Farmaco
• 出版年：2005
• 出版时间：February, 2005
• 年：2005
• 卷：60
• 期：2
• 页码：99-104
• 全文大小：287 K

文摘

Chemical manipulation of the nicotinic agonist DMPP, endowed with modest activity on the central receptors, definitely improved its affinity and pharmacokinetic properties. Although their pharmacophore is somehow different from that of classical nicotinic ligands, some DMPP derivatives show low nanomolar affinity for the central nicotinic receptors. Introduction of rigidity in the structure of DMPP and in that of its analogue 1-(3-pyridyl)piperazine, resulted in molecules with lower or null affinity for the central nicotinic receptors. This suggests that the frozen structures chosen either do not represent the bioactive conformation, or their volume is not compatible with the space available within the interaction site.