Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity

Autores
Slavíková, Barbora; Krištofíková, Zdena; Chodounská, Hana; Buděšínský, Miloš; Duran, Fernando Javier; Veleiro, Adriana Silvia; Burton, Gerardo; Kasal, Alexander
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The lipophilic nature of allopregnanolone prevents its user-friendly application in human medicine. On inspiration by pReviously prepared allopregnanolone with a 16α -bound tetraethylammonium salt, an attempt was made to produce allopregnanolone analogues with polar groups introduced into position 16α with the goal of increasing water solubility, brain accessibility, and potency of neuroactive steroids. The Michael addition to derivatives of pregn-16-en-20-one was the key reaction step. The link between the steroid skeleton and the new side chain was either a methylene group (when diethyl malonate was added) or an oxygen atom (when a hydroxy derivative was added). [35S]TBPS displacement was used to evaluate the products. Several carbamates (but not their parent alcohols) displaced TBPS from the picrotoxin binding site on GABAA receptors. Although none of them was more potent than the above ammonium salt, which stimulated this study, their nonionic nature should not prevent their passage into the brain. © 2009 American Chemical Society.
Fil: Slavíková, Barbora. Academy of Sciences of the Czech Republic; República Checa
Fil: Krištofíková, Zdena. Prague Psychiatric Centre; República Checa
Fil: Chodounská, Hana. Academy of Sciences of the Czech Republic; República Checa
Fil: Buděšínský, Miloš. Academy of Sciences of the Czech Republic; República Checa
Fil: Duran, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina
Fil: Veleiro, Adriana Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina
Fil: Burton, Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina
Fil: Kasal, Alexander. Academy of Sciences of the Czech Republic; República Checa
Materia
NEUROSTEROIDS
ALLOPREGNANOLONE
SULFAMIDATES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/85638
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activitySlavíková, BarboraKrištofíková, ZdenaChodounská, HanaBuděšínský, MilošDuran, Fernando JavierVeleiro, Adriana SilviaBurton, GerardoKasal, AlexanderNEUROSTEROIDSALLOPREGNANOLONESULFAMIDATEShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1The lipophilic nature of allopregnanolone prevents its user-friendly application in human medicine. On inspiration by pReviously prepared allopregnanolone with a 16α -bound tetraethylammonium salt, an attempt was made to produce allopregnanolone analogues with polar groups introduced into position 16α with the goal of increasing water solubility, brain accessibility, and potency of neuroactive steroids. The Michael addition to derivatives of pregn-16-en-20-one was the key reaction step. The link between the steroid skeleton and the new side chain was either a methylene group (when diethyl malonate was added) or an oxygen atom (when a hydroxy derivative was added). [35S]TBPS displacement was used to evaluate the products. Several carbamates (but not their parent alcohols) displaced TBPS from the picrotoxin binding site on GABAA receptors. Although none of them was more potent than the above ammonium salt, which stimulated this study, their nonionic nature should not prevent their passage into the brain. © 2009 American Chemical Society.Fil: Slavíková, Barbora. Academy of Sciences of the Czech Republic; República ChecaFil: Krištofíková, Zdena. Prague Psychiatric Centre; República ChecaFil: Chodounská, Hana. Academy of Sciences of the Czech Republic; República ChecaFil: Buděšínský, Miloš. Academy of Sciences of the Czech Republic; República ChecaFil: Duran, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Veleiro, Adriana Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Burton, Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Kasal, Alexander. Academy of Sciences of the Czech Republic; República ChecaAmerican Chemical Society2009-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/85638Slavíková, Barbora; Krištofíková, Zdena; Chodounská, Hana; Buděšínský, Miloš; Duran, Fernando Javier; et al.; Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity; American Chemical Society; Journal of Medicinal Chemistry; 52; 7; 4-2009; 2119-21250022-2623CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/jm801454ainfo:eu-repo/semantics/altIdentifier/doi/10.1021/jm801454ainfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:48:29Zoai:ri.conicet.gov.ar:11336/85638instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:48:30.157CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity
title Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity
spellingShingle Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity
Slavíková, Barbora
NEUROSTEROIDS
ALLOPREGNANOLONE
SULFAMIDATES
title_short Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity
title_full Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity
title_fullStr Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity
title_full_unstemmed Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity
title_sort Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity
dc.creator.none.fl_str_mv Slavíková, Barbora
Krištofíková, Zdena
Chodounská, Hana
Buděšínský, Miloš
Duran, Fernando Javier
Veleiro, Adriana Silvia
Burton, Gerardo
Kasal, Alexander
author Slavíková, Barbora
author_facet Slavíková, Barbora
Krištofíková, Zdena
Chodounská, Hana
Buděšínský, Miloš
Duran, Fernando Javier
Veleiro, Adriana Silvia
Burton, Gerardo
Kasal, Alexander
author_role author
author2 Krištofíková, Zdena
Chodounská, Hana
Buděšínský, Miloš
Duran, Fernando Javier
Veleiro, Adriana Silvia
Burton, Gerardo
Kasal, Alexander
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv NEUROSTEROIDS
ALLOPREGNANOLONE
SULFAMIDATES
topic NEUROSTEROIDS
ALLOPREGNANOLONE
SULFAMIDATES
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The lipophilic nature of allopregnanolone prevents its user-friendly application in human medicine. On inspiration by pReviously prepared allopregnanolone with a 16α -bound tetraethylammonium salt, an attempt was made to produce allopregnanolone analogues with polar groups introduced into position 16α with the goal of increasing water solubility, brain accessibility, and potency of neuroactive steroids. The Michael addition to derivatives of pregn-16-en-20-one was the key reaction step. The link between the steroid skeleton and the new side chain was either a methylene group (when diethyl malonate was added) or an oxygen atom (when a hydroxy derivative was added). [35S]TBPS displacement was used to evaluate the products. Several carbamates (but not their parent alcohols) displaced TBPS from the picrotoxin binding site on GABAA receptors. Although none of them was more potent than the above ammonium salt, which stimulated this study, their nonionic nature should not prevent their passage into the brain. © 2009 American Chemical Society.
Fil: Slavíková, Barbora. Academy of Sciences of the Czech Republic; República Checa
Fil: Krištofíková, Zdena. Prague Psychiatric Centre; República Checa
Fil: Chodounská, Hana. Academy of Sciences of the Czech Republic; República Checa
Fil: Buděšínský, Miloš. Academy of Sciences of the Czech Republic; República Checa
Fil: Duran, Fernando Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina
Fil: Veleiro, Adriana Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina
Fil: Burton, Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina
Fil: Kasal, Alexander. Academy of Sciences of the Czech Republic; República Checa
description The lipophilic nature of allopregnanolone prevents its user-friendly application in human medicine. On inspiration by pReviously prepared allopregnanolone with a 16α -bound tetraethylammonium salt, an attempt was made to produce allopregnanolone analogues with polar groups introduced into position 16α with the goal of increasing water solubility, brain accessibility, and potency of neuroactive steroids. The Michael addition to derivatives of pregn-16-en-20-one was the key reaction step. The link between the steroid skeleton and the new side chain was either a methylene group (when diethyl malonate was added) or an oxygen atom (when a hydroxy derivative was added). [35S]TBPS displacement was used to evaluate the products. Several carbamates (but not their parent alcohols) displaced TBPS from the picrotoxin binding site on GABAA receptors. Although none of them was more potent than the above ammonium salt, which stimulated this study, their nonionic nature should not prevent their passage into the brain. © 2009 American Chemical Society.
publishDate 2009
dc.date.none.fl_str_mv 2009-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/85638
Slavíková, Barbora; Krištofíková, Zdena; Chodounská, Hana; Buděšínský, Miloš; Duran, Fernando Javier; et al.; Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity; American Chemical Society; Journal of Medicinal Chemistry; 52; 7; 4-2009; 2119-2125
0022-2623
CONICET Digital
CONICET
url http://hdl.handle.net/11336/85638
identifier_str_mv Slavíková, Barbora; Krištofíková, Zdena; Chodounská, Hana; Buděšínský, Miloš; Duran, Fernando Javier; et al.; Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity; American Chemical Society; Journal of Medicinal Chemistry; 52; 7; 4-2009; 2119-2125
0022-2623
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/jm801454a
info:eu-repo/semantics/altIdentifier/doi/10.1021/jm801454a
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842268927218941952
score 12.885934

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