Synthesis and GABAA receptor activity of 2,19-sulfamoyl analogues of allopregnanolone

The synthesis of new analogues of allopregnanolone with a bridged sulfamidate ring over the β-face of ring A has been achieved from easily available precursors, using an intramolecular aziridination strategy. The methodology also allows the synthesis of 3α-substituted analogues such as the 3α-fluoro...

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Autores principales:	Durán, F.J., Edelsztein, V.C., Ghini, A.A., Rey, M., Coirini, H., Dauban, P., Dodd, R.H., Burton, G.
Formato:	JOUR
Materias:	γ-Aminobutyric acid GABAA Neurosteroids Steroids 19 hydroxypregnan 2 en 20 one 3 alpha hydroxy dioxo 19,2 (epoxythioimino)pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 4 aminobutyric acid A receptor benzyl derivative flunitrazepam muscimol n benzyl 3 alpha hydroxy dioxo 19,2 (epoxythioimino)pregnan 20 one neurosteroid pregnane derivative sulfonamide unclassified drug animal tissue article binding affinity controlled study dose response drug receptor binding drug screening drug synthesis nonhuman rat structure activity relation Animals Cell Membrane Cerebellum Male Models, Molecular Pregnanolone Protein Binding Rats Rats, Sprague-Dawley Receptors, GABA-A Structure-Activity Relationship Sulfonamides
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_09680896_v17_n18_p6526_Duran
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_09680896_v17_n18_p6526_Duran2023-10-03T15:55:12Z Synthesis and GABAA receptor activity of 2,19-sulfamoyl analogues of allopregnanolone Durán, F.J. Edelsztein, V.C. Ghini, A.A. Rey, M. Coirini, H. Dauban, P. Dodd, R.H. Burton, G. γ-Aminobutyric acid GABAA Neurosteroids Steroids 19 hydroxypregnan 2 en 20 one 3 alpha hydroxy dioxo 19,2 (epoxythioimino)pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 4 aminobutyric acid A receptor benzyl derivative flunitrazepam muscimol n benzyl 3 alpha hydroxy dioxo 19,2 (epoxythioimino)pregnan 20 one neurosteroid pregnane derivative sulfonamide unclassified drug animal tissue article binding affinity controlled study dose response drug receptor binding drug screening drug synthesis nonhuman rat structure activity relation Animals Cell Membrane Cerebellum Male Models, Molecular Pregnanolone Protein Binding Rats Rats, Sprague-Dawley Receptors, GABA-A Structure-Activity Relationship Sulfonamides The synthesis of new analogues of allopregnanolone with a bridged sulfamidate ring over the β-face of ring A has been achieved from easily available precursors, using an intramolecular aziridination strategy. The methodology also allows the synthesis of 3α-substituted analogues such as the 3α-fluoro derivative. GABAA receptor activity of the synthetic analogues was evaluated by assaying their effect on the binding of [3H]flunitrazepam and [3H]muscimol. The 3α-hydroxy-2,19-sulfamoyl analogue and its N-benzyl derivative were more active than allopregnanolone for stimulating binding of [3H]flunitrazepam. For the binding of [3H]muscimol, both synthetic analogues and allopregnanolone stimulated binding to a similar extent, with the N-benzyl derivative exhibiting a higher EC50. The 3α-fluoro derivative was inactive in both assays. © 2009 Elsevier Ltd. All rights reserved. Fil:Durán, F.J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Edelsztein, V.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ghini, A.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rey, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Coirini, H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Burton, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09680896_v17_n18_p6526_Duran
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	γ-Aminobutyric acid GABAA Neurosteroids Steroids 19 hydroxypregnan 2 en 20 one 3 alpha hydroxy dioxo 19,2 (epoxythioimino)pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 4 aminobutyric acid A receptor benzyl derivative flunitrazepam muscimol n benzyl 3 alpha hydroxy dioxo 19,2 (epoxythioimino)pregnan 20 one neurosteroid pregnane derivative sulfonamide unclassified drug animal tissue article binding affinity controlled study dose response drug receptor binding drug screening drug synthesis nonhuman rat structure activity relation Animals Cell Membrane Cerebellum Male Models, Molecular Pregnanolone Protein Binding Rats Rats, Sprague-Dawley Receptors, GABA-A Structure-Activity Relationship Sulfonamides
spellingShingle	γ-Aminobutyric acid GABAA Neurosteroids Steroids 19 hydroxypregnan 2 en 20 one 3 alpha hydroxy dioxo 19,2 (epoxythioimino)pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 4 aminobutyric acid A receptor benzyl derivative flunitrazepam muscimol n benzyl 3 alpha hydroxy dioxo 19,2 (epoxythioimino)pregnan 20 one neurosteroid pregnane derivative sulfonamide unclassified drug animal tissue article binding affinity controlled study dose response drug receptor binding drug screening drug synthesis nonhuman rat structure activity relation Animals Cell Membrane Cerebellum Male Models, Molecular Pregnanolone Protein Binding Rats Rats, Sprague-Dawley Receptors, GABA-A Structure-Activity Relationship Sulfonamides Durán, F.J. Edelsztein, V.C. Ghini, A.A. Rey, M. Coirini, H. Dauban, P. Dodd, R.H. Burton, G. Synthesis and GABAA receptor activity of 2,19-sulfamoyl analogues of allopregnanolone
topic_facet	γ-Aminobutyric acid GABAA Neurosteroids Steroids 19 hydroxypregnan 2 en 20 one 3 alpha hydroxy dioxo 19,2 (epoxythioimino)pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 4 aminobutyric acid A receptor benzyl derivative flunitrazepam muscimol n benzyl 3 alpha hydroxy dioxo 19,2 (epoxythioimino)pregnan 20 one neurosteroid pregnane derivative sulfonamide unclassified drug animal tissue article binding affinity controlled study dose response drug receptor binding drug screening drug synthesis nonhuman rat structure activity relation Animals Cell Membrane Cerebellum Male Models, Molecular Pregnanolone Protein Binding Rats Rats, Sprague-Dawley Receptors, GABA-A Structure-Activity Relationship Sulfonamides
description	The synthesis of new analogues of allopregnanolone with a bridged sulfamidate ring over the β-face of ring A has been achieved from easily available precursors, using an intramolecular aziridination strategy. The methodology also allows the synthesis of 3α-substituted analogues such as the 3α-fluoro derivative. GABAA receptor activity of the synthetic analogues was evaluated by assaying their effect on the binding of [3H]flunitrazepam and [3H]muscimol. The 3α-hydroxy-2,19-sulfamoyl analogue and its N-benzyl derivative were more active than allopregnanolone for stimulating binding of [3H]flunitrazepam. For the binding of [3H]muscimol, both synthetic analogues and allopregnanolone stimulated binding to a similar extent, with the N-benzyl derivative exhibiting a higher EC50. The 3α-fluoro derivative was inactive in both assays. © 2009 Elsevier Ltd. All rights reserved.
format	JOUR
author	Durán, F.J. Edelsztein, V.C. Ghini, A.A. Rey, M. Coirini, H. Dauban, P. Dodd, R.H. Burton, G.
author_facet	Durán, F.J. Edelsztein, V.C. Ghini, A.A. Rey, M. Coirini, H. Dauban, P. Dodd, R.H. Burton, G.
author_sort	Durán, F.J.
title	Synthesis and GABAA receptor activity of 2,19-sulfamoyl analogues of allopregnanolone
title_short	Synthesis and GABAA receptor activity of 2,19-sulfamoyl analogues of allopregnanolone
title_full	Synthesis and GABAA receptor activity of 2,19-sulfamoyl analogues of allopregnanolone
title_fullStr	Synthesis and GABAA receptor activity of 2,19-sulfamoyl analogues of allopregnanolone
title_full_unstemmed	Synthesis and GABAA receptor activity of 2,19-sulfamoyl analogues of allopregnanolone
title_sort	synthesis and gabaa receptor activity of 2,19-sulfamoyl analogues of allopregnanolone
url	http://hdl.handle.net/20.500.12110/paper_09680896_v17_n18_p6526_Duran
work_keys_str_mv	AT duranfj synthesisandgabaareceptoractivityof219sulfamoylanaloguesofallopregnanolone AT edelszteinvc synthesisandgabaareceptoractivityof219sulfamoylanaloguesofallopregnanolone AT ghiniaa synthesisandgabaareceptoractivityof219sulfamoylanaloguesofallopregnanolone AT reym synthesisandgabaareceptoractivityof219sulfamoylanaloguesofallopregnanolone AT coirinih synthesisandgabaareceptoractivityof219sulfamoylanaloguesofallopregnanolone AT daubanp synthesisandgabaareceptoractivityof219sulfamoylanaloguesofallopregnanolone AT doddrh synthesisandgabaareceptoractivityof219sulfamoylanaloguesofallopregnanolone AT burtong synthesisandgabaareceptoractivityof219sulfamoylanaloguesofallopregnanolone
_version_	1807318901698068480

Synthesis and GABAA receptor activity of 2,19-sulfamoyl analogues of allopregnanolone

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