Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids

A procedure is described for the preparation of A-homo-5-pregnenes via an acid catalyzed rearrangement of cyclopropylcarbinols assisted by microwave irradiation. 3α-Hydroxy and 4α-hydroxy-A-homo-5- pregnen-20-one, analogues of the neuroactive steroid allopregnanolone, were obtained by means of a reg...

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Autores principales:	Dansey, M.V., Di Chenna, P.H., Veleiro, A.S., Krištofíková, Z., Chodounska, H., Kasal, A., Burton, G.
Formato:	JOUR
Materias:	A-homopregnane GABAA receptor Neurosteroid γ-Aminobutyric acid 3alpha hydroxy 5alpha pregnan 20 one 3alpha hydroxy a homo 5 pregnen 20 one 3beta hydroxy a homo 5 pregnen 20 one 3beta hydroxy a homo 5alpha h pregnan 20 one 4 aminobutyric acid A receptor 4alpha hydroxy a homo 5 pregnen 20 one fructose ketone methanol derivative neuroactive steroid neurosteroid oxidizing agent pregnane derivative sodium peroxide tert butylbicyclophosphorothioate unclassified drug fused heterocyclic rings hydroxide hydroxide ion tert-butylbicyclophosphorothionate article binding affinity catalysis catalyst chemical bond chirality controlled study drug conformation drug synthesis epoxidation microwave irradiation reaction analysis receptor binding ring opening stereochemistry animal chemical structure chemistry conformation drug effect male metabolism microwave radiation protein binding rat synthesis Wistar rat Animals Bicyclo Compounds, Heterocyclic Hydroxides Male Microwaves Models, Molecular Molecular Conformation Pregnenes Protein Binding Rats Rats, Wistar Receptors, GABA-A
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_02235234_v45_n7_p3063_Dansey
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_02235234_v45_n7_p3063_Dansey2023-10-03T15:11:13Z Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids Dansey, M.V. Di Chenna, P.H. Veleiro, A.S. Krištofíková, Z. Chodounska, H. Kasal, A. Burton, G. A-homopregnane GABAA receptor Neurosteroid γ-Aminobutyric acid 3alpha hydroxy 5alpha pregnan 20 one 3alpha hydroxy a homo 5 pregnen 20 one 3beta hydroxy a homo 5 pregnen 20 one 3beta hydroxy a homo 5alpha h pregnan 20 one 4 aminobutyric acid A receptor 4alpha hydroxy a homo 5 pregnen 20 one fructose ketone methanol derivative neuroactive steroid neurosteroid oxidizing agent pregnane derivative sodium peroxide tert butylbicyclophosphorothioate unclassified drug 4 aminobutyric acid A receptor fused heterocyclic rings hydroxide hydroxide ion pregnane derivative tert butylbicyclophosphorothioate tert-butylbicyclophosphorothionate article binding affinity catalysis catalyst chemical bond chirality controlled study drug conformation drug synthesis epoxidation microwave irradiation reaction analysis receptor binding ring opening stereochemistry animal chemical structure chemistry conformation drug effect male metabolism microwave radiation protein binding rat synthesis Wistar rat Animals Bicyclo Compounds, Heterocyclic Hydroxides Male Microwaves Models, Molecular Molecular Conformation Pregnenes Protein Binding Rats Rats, Wistar Receptors, GABA-A A procedure is described for the preparation of A-homo-5-pregnenes via an acid catalyzed rearrangement of cyclopropylcarbinols assisted by microwave irradiation. 3α-Hydroxy and 4α-hydroxy-A-homo-5- pregnen-20-one, analogues of the neuroactive steroid allopregnanolone, were obtained by means of a regioselective epoxidation of a double bond in the expanded A-ring, using a fructose-derived chiral ketone as catalyst and oxone as oxidant. Although both these compounds were marginally active in inhibiting TBPS binding to GABA A receptors, 3β-hydroxy-A-homo-5-pregnen-20-one was almost as active as allopregnanolone. Reduction of the double bond of the latter compound resulted in a ten fold loss of activity. © 2010 Elsevier Masson SAS. Fil:Dansey, M.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Di Chenna, P.H. 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: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_02235234_v45_n7_p3063_Dansey
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	A-homopregnane GABAA receptor Neurosteroid γ-Aminobutyric acid 3alpha hydroxy 5alpha pregnan 20 one 3alpha hydroxy a homo 5 pregnen 20 one 3beta hydroxy a homo 5 pregnen 20 one 3beta hydroxy a homo 5alpha h pregnan 20 one 4 aminobutyric acid A receptor 4alpha hydroxy a homo 5 pregnen 20 one fructose ketone methanol derivative neuroactive steroid neurosteroid oxidizing agent pregnane derivative sodium peroxide tert butylbicyclophosphorothioate unclassified drug 4 aminobutyric acid A receptor fused heterocyclic rings hydroxide hydroxide ion pregnane derivative tert butylbicyclophosphorothioate tert-butylbicyclophosphorothionate article binding affinity catalysis catalyst chemical bond chirality controlled study drug conformation drug synthesis epoxidation microwave irradiation reaction analysis receptor binding ring opening stereochemistry animal chemical structure chemistry conformation drug effect male metabolism microwave radiation protein binding rat synthesis Wistar rat Animals Bicyclo Compounds, Heterocyclic Hydroxides Male Microwaves Models, Molecular Molecular Conformation Pregnenes Protein Binding Rats Rats, Wistar Receptors, GABA-A
spellingShingle	A-homopregnane GABAA receptor Neurosteroid γ-Aminobutyric acid 3alpha hydroxy 5alpha pregnan 20 one 3alpha hydroxy a homo 5 pregnen 20 one 3beta hydroxy a homo 5 pregnen 20 one 3beta hydroxy a homo 5alpha h pregnan 20 one 4 aminobutyric acid A receptor 4alpha hydroxy a homo 5 pregnen 20 one fructose ketone methanol derivative neuroactive steroid neurosteroid oxidizing agent pregnane derivative sodium peroxide tert butylbicyclophosphorothioate unclassified drug 4 aminobutyric acid A receptor fused heterocyclic rings hydroxide hydroxide ion pregnane derivative tert butylbicyclophosphorothioate tert-butylbicyclophosphorothionate article binding affinity catalysis catalyst chemical bond chirality controlled study drug conformation drug synthesis epoxidation microwave irradiation reaction analysis receptor binding ring opening stereochemistry animal chemical structure chemistry conformation drug effect male metabolism microwave radiation protein binding rat synthesis Wistar rat Animals Bicyclo Compounds, Heterocyclic Hydroxides Male Microwaves Models, Molecular Molecular Conformation Pregnenes Protein Binding Rats Rats, Wistar Receptors, GABA-A Dansey, M.V. Di Chenna, P.H. Veleiro, A.S. Krištofíková, Z. Chodounska, H. Kasal, A. Burton, G. Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids
topic_facet	A-homopregnane GABAA receptor Neurosteroid γ-Aminobutyric acid 3alpha hydroxy 5alpha pregnan 20 one 3alpha hydroxy a homo 5 pregnen 20 one 3beta hydroxy a homo 5 pregnen 20 one 3beta hydroxy a homo 5alpha h pregnan 20 one 4 aminobutyric acid A receptor 4alpha hydroxy a homo 5 pregnen 20 one fructose ketone methanol derivative neuroactive steroid neurosteroid oxidizing agent pregnane derivative sodium peroxide tert butylbicyclophosphorothioate unclassified drug 4 aminobutyric acid A receptor fused heterocyclic rings hydroxide hydroxide ion pregnane derivative tert butylbicyclophosphorothioate tert-butylbicyclophosphorothionate article binding affinity catalysis catalyst chemical bond chirality controlled study drug conformation drug synthesis epoxidation microwave irradiation reaction analysis receptor binding ring opening stereochemistry animal chemical structure chemistry conformation drug effect male metabolism microwave radiation protein binding rat synthesis Wistar rat Animals Bicyclo Compounds, Heterocyclic Hydroxides Male Microwaves Models, Molecular Molecular Conformation Pregnenes Protein Binding Rats Rats, Wistar Receptors, GABA-A
description	A procedure is described for the preparation of A-homo-5-pregnenes via an acid catalyzed rearrangement of cyclopropylcarbinols assisted by microwave irradiation. 3α-Hydroxy and 4α-hydroxy-A-homo-5- pregnen-20-one, analogues of the neuroactive steroid allopregnanolone, were obtained by means of a regioselective epoxidation of a double bond in the expanded A-ring, using a fructose-derived chiral ketone as catalyst and oxone as oxidant. Although both these compounds were marginally active in inhibiting TBPS binding to GABA A receptors, 3β-hydroxy-A-homo-5-pregnen-20-one was almost as active as allopregnanolone. Reduction of the double bond of the latter compound resulted in a ten fold loss of activity. © 2010 Elsevier Masson SAS.
format	JOUR
author	Dansey, M.V. Di Chenna, P.H. Veleiro, A.S. Krištofíková, Z. Chodounska, H. Kasal, A. Burton, G.
author_facet	Dansey, M.V. Di Chenna, P.H. Veleiro, A.S. Krištofíková, Z. Chodounska, H. Kasal, A. Burton, G.
author_sort	Dansey, M.V.
title	Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids
title_short	Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids
title_full	Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids
title_fullStr	Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids
title_full_unstemmed	Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids
title_sort	synthesis and gabaa receptor activity of a-homo analogues of neuroactive steroids
url	http://hdl.handle.net/20.500.12110/paper_02235234_v45_n7_p3063_Dansey
work_keys_str_mv	AT danseymv synthesisandgabaareceptoractivityofahomoanaloguesofneuroactivesteroids AT dichennaph synthesisandgabaareceptoractivityofahomoanaloguesofneuroactivesteroids AT veleiroas synthesisandgabaareceptoractivityofahomoanaloguesofneuroactivesteroids AT kristofikovaz synthesisandgabaareceptoractivityofahomoanaloguesofneuroactivesteroids AT chodounskah synthesisandgabaareceptoractivityofahomoanaloguesofneuroactivesteroids AT kasala synthesisandgabaareceptoractivityofahomoanaloguesofneuroactivesteroids AT burtong synthesisandgabaareceptoractivityofahomoanaloguesofneuroactivesteroids
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Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids

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