Design, synthesis, and pharmacological characterization of novel spirocyclic quinuclidinyl-Delta2 -isoxazoline derivatives as potent and selective agonists of alpha7 nicotinic acetylcholine receptors

Research output: Contribution to journalJournal articleResearchpeer-review

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Design, synthesis, and pharmacological characterization of novel spirocyclic quinuclidinyl-Delta2 -isoxazoline derivatives as potent and selective agonists of alpha7 nicotinic acetylcholine receptors. / Dallanoce, Clelia; Magrone, Pietro; Matera, Carlo; Frigerio, Fabio; Grazioso, Giovanni; De Amici, Marco; Fucile, Sergio; Piccari, Vanessa; Frydenvang, Karla Andrea; Pucci, Luca; Gotti, Cecilia; Clementi, Francesco; De Micheli, Carlo.

In: ChemMedChem, Vol. 6, No. 5, 02.05.2011, p. 889-903.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Dallanoce, C, Magrone, P, Matera, C, Frigerio, F, Grazioso, G, De Amici, M, Fucile, S, Piccari, V, Frydenvang, KA, Pucci, L, Gotti, C, Clementi, F & De Micheli, C 2011, 'Design, synthesis, and pharmacological characterization of novel spirocyclic quinuclidinyl-Delta2 -isoxazoline derivatives as potent and selective agonists of alpha7 nicotinic acetylcholine receptors', ChemMedChem, vol. 6, no. 5, pp. 889-903. https://doi.org/10.1002/cmdc.201000514

APA

Dallanoce, C., Magrone, P., Matera, C., Frigerio, F., Grazioso, G., De Amici, M., ... De Micheli, C. (2011). Design, synthesis, and pharmacological characterization of novel spirocyclic quinuclidinyl-Delta2 -isoxazoline derivatives as potent and selective agonists of alpha7 nicotinic acetylcholine receptors. ChemMedChem, 6(5), 889-903. https://doi.org/10.1002/cmdc.201000514

Vancouver

Dallanoce C, Magrone P, Matera C, Frigerio F, Grazioso G, De Amici M et al. Design, synthesis, and pharmacological characterization of novel spirocyclic quinuclidinyl-Delta2 -isoxazoline derivatives as potent and selective agonists of alpha7 nicotinic acetylcholine receptors. ChemMedChem. 2011 May 2;6(5):889-903. https://doi.org/10.1002/cmdc.201000514

Author

Dallanoce, Clelia ; Magrone, Pietro ; Matera, Carlo ; Frigerio, Fabio ; Grazioso, Giovanni ; De Amici, Marco ; Fucile, Sergio ; Piccari, Vanessa ; Frydenvang, Karla Andrea ; Pucci, Luca ; Gotti, Cecilia ; Clementi, Francesco ; De Micheli, Carlo. / Design, synthesis, and pharmacological characterization of novel spirocyclic quinuclidinyl-Delta2 -isoxazoline derivatives as potent and selective agonists of alpha7 nicotinic acetylcholine receptors. In: ChemMedChem. 2011 ; Vol. 6, No. 5. pp. 889-903.

Bibtex

@article{7a5f5954ad28455a8dda0f53a1fe39fc,
title = "Design, synthesis, and pharmacological characterization of novel spirocyclic quinuclidinyl-Delta2 -isoxazoline derivatives as potent and selective agonists of alpha7 nicotinic acetylcholine receptors",
abstract = "A set of racemic spirocyclic quinuclidinyl-¿(2) -isoxazoline derivatives was synthesized using a 1,3-dipolar cycloaddition-based approach. Target compounds were assayed for binding affinity toward rat neuronal homomeric (a7) and heteromeric (a4{\ss}2) nicotinic acetylcholine receptors. ¿(2) -Isoxazolines 3¿a (3-Br), 6¿a (3-OMe), 5¿a (3-Ph), 8¿a (3-OnPr), and 4¿a (3-Me) were the ligands with the highest affinity for the a7 subtype (K(i) values equal to 13.5, 14.2, 25.0, 71.6, and 96.2 nM, respectively), and showed excellent a7 versus a4{\ss}2 subtype selectivity. These compounds, tested in electrophysiological experiments against human a7 and a4{\ss}2 receptors stably expressed in cell lines, behaved as partial a7 agonists with varying levels of potency. The two enantiomers of (±)-3-methoxy-1-oxa-2,7-diaza-7,10-ethanospiro[4.5]dec-2-ene sesquifumarate 6¿a were prepared using (+)-dibenzoyl-L- or (-)-dibenzoyl-D-tartaric acid as resolving agents. Enantiomer (R)-(-)-6¿a was found to be the eutomer, with K(i) values of 4.6 and 48.7 nM against rat and human a7 receptors, respectively.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Clelia Dallanoce and Pietro Magrone and Carlo Matera and Fabio Frigerio and Giovanni Grazioso and {De Amici}, Marco and Sergio Fucile and Vanessa Piccari and Frydenvang, {Karla Andrea} and Luca Pucci and Cecilia Gotti and Francesco Clementi and {De Micheli}, Carlo",
note = "Copyright {\circledC} 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
year = "2011",
month = "5",
day = "2",
doi = "10.1002/cmdc.201000514",
language = "English",
volume = "6",
pages = "889--903",
journal = "ChemMedChem",
issn = "1860-7179",
publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",
number = "5",

}

RIS

TY - JOUR

T1 - Design, synthesis, and pharmacological characterization of novel spirocyclic quinuclidinyl-Delta2 -isoxazoline derivatives as potent and selective agonists of alpha7 nicotinic acetylcholine receptors

AU - Dallanoce, Clelia

AU - Magrone, Pietro

AU - Matera, Carlo

AU - Frigerio, Fabio

AU - Grazioso, Giovanni

AU - De Amici, Marco

AU - Fucile, Sergio

AU - Piccari, Vanessa

AU - Frydenvang, Karla Andrea

AU - Pucci, Luca

AU - Gotti, Cecilia

AU - Clementi, Francesco

AU - De Micheli, Carlo

N1 - Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2011/5/2

Y1 - 2011/5/2

N2 - A set of racemic spirocyclic quinuclidinyl-¿(2) -isoxazoline derivatives was synthesized using a 1,3-dipolar cycloaddition-based approach. Target compounds were assayed for binding affinity toward rat neuronal homomeric (a7) and heteromeric (a4ß2) nicotinic acetylcholine receptors. ¿(2) -Isoxazolines 3¿a (3-Br), 6¿a (3-OMe), 5¿a (3-Ph), 8¿a (3-OnPr), and 4¿a (3-Me) were the ligands with the highest affinity for the a7 subtype (K(i) values equal to 13.5, 14.2, 25.0, 71.6, and 96.2 nM, respectively), and showed excellent a7 versus a4ß2 subtype selectivity. These compounds, tested in electrophysiological experiments against human a7 and a4ß2 receptors stably expressed in cell lines, behaved as partial a7 agonists with varying levels of potency. The two enantiomers of (±)-3-methoxy-1-oxa-2,7-diaza-7,10-ethanospiro[4.5]dec-2-ene sesquifumarate 6¿a were prepared using (+)-dibenzoyl-L- or (-)-dibenzoyl-D-tartaric acid as resolving agents. Enantiomer (R)-(-)-6¿a was found to be the eutomer, with K(i) values of 4.6 and 48.7 nM against rat and human a7 receptors, respectively.

AB - A set of racemic spirocyclic quinuclidinyl-¿(2) -isoxazoline derivatives was synthesized using a 1,3-dipolar cycloaddition-based approach. Target compounds were assayed for binding affinity toward rat neuronal homomeric (a7) and heteromeric (a4ß2) nicotinic acetylcholine receptors. ¿(2) -Isoxazolines 3¿a (3-Br), 6¿a (3-OMe), 5¿a (3-Ph), 8¿a (3-OnPr), and 4¿a (3-Me) were the ligands with the highest affinity for the a7 subtype (K(i) values equal to 13.5, 14.2, 25.0, 71.6, and 96.2 nM, respectively), and showed excellent a7 versus a4ß2 subtype selectivity. These compounds, tested in electrophysiological experiments against human a7 and a4ß2 receptors stably expressed in cell lines, behaved as partial a7 agonists with varying levels of potency. The two enantiomers of (±)-3-methoxy-1-oxa-2,7-diaza-7,10-ethanospiro[4.5]dec-2-ene sesquifumarate 6¿a were prepared using (+)-dibenzoyl-L- or (-)-dibenzoyl-D-tartaric acid as resolving agents. Enantiomer (R)-(-)-6¿a was found to be the eutomer, with K(i) values of 4.6 and 48.7 nM against rat and human a7 receptors, respectively.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1002/cmdc.201000514

DO - 10.1002/cmdc.201000514

M3 - Journal article

C2 - 21365765

VL - 6

SP - 889

EP - 903

JO - ChemMedChem

JF - ChemMedChem

SN - 1860-7179

IS - 5

ER -

ID: 33171335