Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs

Three analogs of neuroactive steroids were prepared (4-6) in which 1,11- or 11,19-oxygen bridges give a constrained conformation. Their 3D structures were obtained by ab initio calculations and in the case of 3α-hydroxy-11,19-epoxypregn-4-ene-20-one (4), confirmed by X-ray analysis. Biological activ...

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Autores principales:	Alvarez, L.D., Veleiro, A.S., Baggio, R.F., Garland, M.T., Edelsztein, V.C., Coirini, H., Burton, G.
Formato:	JOUR
Materias:	γ-Aminobutyric acid GABA GABAA receptor Neurosteroids Steroids 3alpha hydroxy 11,19 epoxypregn 4 ene 20 one 3alpha hydroxy 1alpha,11alpha epoxy 5beta pregnan 20 one 3alpha hydroxy 1beta,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 4 aminobutyric acid A receptor eltanolone neurosteroid oxygen tert butylbicycloorthobenzoate tritium unclassified drug ab initio calculation article biological activity controlled study drug conformation drug receptor binding drug structure in vitro study isotope labeling male nonhuman rat X ray analysis Animals Male Models, Molecular Molecular Structure Neurons Oxygen Rats Rats, Sprague-Dawley Receptors, GABA-A
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_09680896_v16_n7_p3831_Alvarez
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_09680896_v16_n7_p3831_Alvarez
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spelling	todo:paper_09680896_v16_n7_p3831_Alvarez2023-10-03T15:55:12Z Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs Alvarez, L.D. Veleiro, A.S. Baggio, R.F. Garland, M.T. Edelsztein, V.C. Coirini, H. Burton, G. γ-Aminobutyric acid GABA GABAA receptor Neurosteroids Steroids 3alpha hydroxy 11,19 epoxypregn 4 ene 20 one 3alpha hydroxy 1alpha,11alpha epoxy 5beta pregnan 20 one 3alpha hydroxy 1beta,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 4 aminobutyric acid A receptor eltanolone neurosteroid oxygen tert butylbicycloorthobenzoate tritium unclassified drug ab initio calculation article biological activity controlled study drug conformation drug receptor binding drug structure in vitro study isotope labeling male nonhuman rat X ray analysis Animals Male Models, Molecular Molecular Structure Neurons Oxygen Rats Rats, Sprague-Dawley Receptors, GABA-A Steroids Three analogs of neuroactive steroids were prepared (4-6) in which 1,11- or 11,19-oxygen bridges give a constrained conformation. Their 3D structures were obtained by ab initio calculations and in the case of 3α-hydroxy-11,19-epoxypregn-4-ene-20-one (4), confirmed by X-ray analysis. Biological activity of the synthetic steroids was assayed in vitro using t-[3H]butylbicycloorthobenzoate as radiolabeled ligand for the GABAA receptor. The activity of compound 4 was similar to that of allopregnanolone (1). 1α,11α-Epoxypregnanolone (6) was more active than pregnanolone (2). © 2008 Elsevier Ltd. All rights reserved. Fil:Alvarez, L.D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Veleiro, A.S. 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: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_v16_n7_p3831_Alvarez
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 GABA GABAA receptor Neurosteroids Steroids 3alpha hydroxy 11,19 epoxypregn 4 ene 20 one 3alpha hydroxy 1alpha,11alpha epoxy 5beta pregnan 20 one 3alpha hydroxy 1beta,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 4 aminobutyric acid A receptor eltanolone neurosteroid oxygen tert butylbicycloorthobenzoate tritium unclassified drug ab initio calculation article biological activity controlled study drug conformation drug receptor binding drug structure in vitro study isotope labeling male nonhuman rat X ray analysis Animals Male Models, Molecular Molecular Structure Neurons Oxygen Rats Rats, Sprague-Dawley Receptors, GABA-A Steroids
spellingShingle	γ-Aminobutyric acid GABA GABAA receptor Neurosteroids Steroids 3alpha hydroxy 11,19 epoxypregn 4 ene 20 one 3alpha hydroxy 1alpha,11alpha epoxy 5beta pregnan 20 one 3alpha hydroxy 1beta,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 4 aminobutyric acid A receptor eltanolone neurosteroid oxygen tert butylbicycloorthobenzoate tritium unclassified drug ab initio calculation article biological activity controlled study drug conformation drug receptor binding drug structure in vitro study isotope labeling male nonhuman rat X ray analysis Animals Male Models, Molecular Molecular Structure Neurons Oxygen Rats Rats, Sprague-Dawley Receptors, GABA-A Steroids Alvarez, L.D. Veleiro, A.S. Baggio, R.F. Garland, M.T. Edelsztein, V.C. Coirini, H. Burton, G. Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs
topic_facet	γ-Aminobutyric acid GABA GABAA receptor Neurosteroids Steroids 3alpha hydroxy 11,19 epoxypregn 4 ene 20 one 3alpha hydroxy 1alpha,11alpha epoxy 5beta pregnan 20 one 3alpha hydroxy 1beta,11alpha epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 4 aminobutyric acid A receptor eltanolone neurosteroid oxygen tert butylbicycloorthobenzoate tritium unclassified drug ab initio calculation article biological activity controlled study drug conformation drug receptor binding drug structure in vitro study isotope labeling male nonhuman rat X ray analysis Animals Male Models, Molecular Molecular Structure Neurons Oxygen Rats Rats, Sprague-Dawley Receptors, GABA-A Steroids
description	Three analogs of neuroactive steroids were prepared (4-6) in which 1,11- or 11,19-oxygen bridges give a constrained conformation. Their 3D structures were obtained by ab initio calculations and in the case of 3α-hydroxy-11,19-epoxypregn-4-ene-20-one (4), confirmed by X-ray analysis. Biological activity of the synthetic steroids was assayed in vitro using t-[3H]butylbicycloorthobenzoate as radiolabeled ligand for the GABAA receptor. The activity of compound 4 was similar to that of allopregnanolone (1). 1α,11α-Epoxypregnanolone (6) was more active than pregnanolone (2). © 2008 Elsevier Ltd. All rights reserved.
format	JOUR
author	Alvarez, L.D. Veleiro, A.S. Baggio, R.F. Garland, M.T. Edelsztein, V.C. Coirini, H. Burton, G.
author_facet	Alvarez, L.D. Veleiro, A.S. Baggio, R.F. Garland, M.T. Edelsztein, V.C. Coirini, H. Burton, G.
author_sort	Alvarez, L.D.
title	Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs
title_short	Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs
title_full	Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs
title_fullStr	Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs
title_full_unstemmed	Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs
title_sort	synthesis and gabaa receptor activity of oxygen-bridged neurosteroid analogs
url	http://hdl.handle.net/20.500.12110/paper_09680896_v16_n7_p3831_Alvarez
work_keys_str_mv	AT alvarezld synthesisandgabaareceptoractivityofoxygenbridgedneurosteroidanalogs AT veleiroas synthesisandgabaareceptoractivityofoxygenbridgedneurosteroidanalogs AT baggiorf synthesisandgabaareceptoractivityofoxygenbridgedneurosteroidanalogs AT garlandmt synthesisandgabaareceptoractivityofoxygenbridgedneurosteroidanalogs AT edelszteinvc synthesisandgabaareceptoractivityofoxygenbridgedneurosteroidanalogs AT coirinih synthesisandgabaareceptoractivityofoxygenbridgedneurosteroidanalogs AT burtong synthesisandgabaareceptoractivityofoxygenbridgedneurosteroidanalogs
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Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs

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