Artículo

Slavíková, B.; Krištofíková, Z.; Chodounská, H.; Buděšínský, M.; Durán, F.J.; Veleiro, A.S.; Burton, G.; Kasal, A. "Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity" (2009) Journal of Medicinal Chemistry. 52(7):2119-2125
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Abstract:

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.

Registro:

Documento: Artículo
Título:Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity
Autor:Slavíková, B.; Krištofíková, Z.; Chodounská, H.; Buděšínský, M.; Durán, F.J.; Veleiro, A.S.; Burton, G.; Kasal, A.
Filiación:Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, CZ16610 Prague 6, Czech Republic
Prague Psychiatric Centre, Ústavní 91, CZ18103 Prague, Czech Republic
Departamento de Química Orgánica and UMYMFOR (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad UniVersitaria, C1428EHA, Buenos Aires, Argentina
Palabras clave:16alpha bis(carbamoyloxymethyl)methyl 3alpha hydroxy 5alpha pregnan 20 one; 16alpha carbamoyloxyethyl 3alpha hydroxy 5alpha pregnan 20 one; 16alpha ethyl 20 oxo 5alpha pregnane 3alpha,16b diyl dicarbamate; 16alpha ethyl 20 oxo 5alpha pregnane 3r,16b diyl dicarbamate; 20,20 ethylenedioxy 16r bis(methoxycarbonyl)methyl 5alpha pregnan 3alpha ol; 3alpha hydroxy 16alpha (2 hydroxyethoxy) 5alpha pregnan 20 one; 3alpha hydroxy 16alpha (2,3 dihydroxypropoxy) 5alpha pregnan 20 one; 3alpha hydroxy 16alpha [2 hydroxy (2 ethoxyethoxy)] 5alpha pregnan 20 one; 3alpha hydroxy 16alpha bis(methoxycarbonyl)methyl 5alpha pregnan 20 one; 3alpha hydroxy 16alpha methoxycarbonylmethyl 5alpha pregnan 20 one; 3alpha hydroxy 16alpha-bis(hydroxymethyl)methyl 5alpha pregnan 20 one; 3alpha hydroxy 5alpha pregnan 20 one; 3alpha tert butyldimethylsilyloxy 16alpha ethyl 20,20 ethylenedioxy 5alpha pregnan 16b ol; 3alpha tert butyldimethylsilyloxy 20,20 ethylenedioxy 16alpha bis(hydroxymethyl)methyl 5alpha pregnane; 3beta hydroxy 16ralpha (2' hydroxyethoxy) pregn 5 en 20 one; 3r tert butyldimethylsilyloxy 20,20 ethylenedioxy 16r bis (methoxycarbonyl)methyl 5alpha pregnane; 4 aminobutyric acid A receptor; unclassified drug; benzodiazepine receptor affecting agent; drug derivative; eltanolone; article; binding site; drug activity; drug binding; drug structure; drug synthesis; animal; brain; in vitro study; male; metabolism; radioassay; rat; structure activity relation; synthesis; Wistar rat; Animals; Brain; GABA Modulators; Male; Pregnanolone; Radioligand Assay; Rats; Rats, Wistar; Receptors, GABA-A; Structure-Activity Relationship
Año:2009
Volumen:52
Número:7
Página de inicio:2119
Página de fin:2125
DOI: http://dx.doi.org/10.1021/jm801454a
Título revista:Journal of Medicinal Chemistry
Título revista abreviado:J. Med. Chem.
ISSN:00222623
CODEN:JMCMA
CAS:3alpha hydroxy 5alpha pregnan 20 one, 516-54-1; eltanolone, 128-20-1; GABA Modulators; Pregnanolone, 128-20-1; Receptors, GABA-A
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00222623_v52_n7_p2119_Slavikova

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Citas:

---------- APA ----------
Slavíková, B., Krištofíková, Z., Chodounská, H., Buděšínský, M., Durán, F.J., Veleiro, A.S., Burton, G.,..., Kasal, A. (2009) . Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity. Journal of Medicinal Chemistry, 52(7), 2119-2125.
http://dx.doi.org/10.1021/jm801454a
---------- CHICAGO ----------
Slavíková, B., Krištofíková, Z., Chodounská, H., Buděšínský, M., Durán, F.J., Veleiro, A.S., et al. "Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity" . Journal of Medicinal Chemistry 52, no. 7 (2009) : 2119-2125.
http://dx.doi.org/10.1021/jm801454a
---------- MLA ----------
Slavíková, B., Krištofíková, Z., Chodounská, H., Buděšínský, M., Durán, F.J., Veleiro, A.S., et al. "Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity" . Journal of Medicinal Chemistry, vol. 52, no. 7, 2009, pp. 2119-2125.
http://dx.doi.org/10.1021/jm801454a
---------- VANCOUVER ----------
Slavíková, B., Krištofíková, Z., Chodounská, H., Buděšínský, M., Durán, F.J., Veleiro, A.S., et al. Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) derivatives with a polar chain in position 16α: Synthesis and activity. J. Med. Chem. 2009;52(7):2119-2125.
http://dx.doi.org/10.1021/jm801454a