Novel tricyclic Delta(2)-isoxazoline and 3-oxo-2-methyl-isoxazolidine derivatives: synthesis and binding affinity at neuronal nicotinic acetylcholine receptor subtypes.


:A group of novel tricyclic Delta(2)-isoxazolines (4b, 5b, 7a-b, and 8a-b) and 3-oxo-isoxazolidines (6a-b and 9a-b), structurally related to cytisine or norferruginine, was prepared through 1,3-dipolar cycloadditions involving suitable olefins and bromonitrile oxide. The target compounds were assayed at alpha4beta2 and alpha7 neuronal acetylcholine receptors (nAChRs). The results of competition binding experiments indicated for the new derivatives a reduction of the affinity at the alpha4beta2 subtype in comparison with the reference molecules, coupled with an overall negligible affinity at the alpha7 subtype. The binding mode of the bromo-Delta(2)-isoxazolines 4b and 7b, which were the highest affinity ligands in the series (K(i)=0.92 and 0.75 microM, respectively), was analyzed by applying a recently developed model of the alpha4beta2 nAChRs.


Bioorg Med Chem


Dallanoce C,Frigerio F,Martelli G,Grazioso G,Matera C,Pomè DY,Pucci L,Clementi F,Gotti C,De Amici M




Has Abstract


2010-06-15 00:00:00














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    pub_type: 杂志文章


    authors: Seerden JP,Tulp MT,Scheeren HW,Kruse CG

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    pub_type: 杂志文章


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    更新日期:2013-09-01 00:00:00

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    pub_type: 杂志文章


    authors: Batista R,Humberto JL,Chiari E,de Oliveira AB

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


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