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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" (2009) Bioorganic and Medicinal Chemistry. 17(18):6526-6533
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Abstract:

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.

Registro:

Documento: Artículo
Título:Synthesis and GABAA receptor activity of 2,19-sulfamoyl analogues of allopregnanolone
Autor:Durán, F.J.; Edelsztein, V.C.; Ghini, A.A.; Rey, M.; Coirini, H.; Dauban, P.; Dodd, R.H.; Burton, G.
Filiación:Departamento de Química Orgánica and UMYMFOR (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellon 2, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina
Instituto de Biología y Medicina Experimental (CONICET), Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina
Institut de Chimie des Substances Naturelles, UPR 2301, CNRS, 91198 Gif-sur-Yvette, France
Palabras clave: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
Año:2009
Volumen:17
Número:18
Página de inicio:6526
Página de fin:6533
DOI: http://dx.doi.org/10.1016/j.bmc.2009.08.008
Título revista:Bioorganic and Medicinal Chemistry
Título revista abreviado:Bioorg. Med. Chem.
ISSN:09680896
CODEN:BMECE
CAS:3alpha hydroxy 5alpha pregnan 20 one, 516-54-1; flunitrazepam, 1622-62-4; muscimol, 2763-96-4; Pregnanolone, 128-20-1; Receptors, GABA-A; Sulfonamides
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09680896_v17_n18_p6526_Duran

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Citas:

---------- APA ----------
Durán, F.J., Edelsztein, V.C., Ghini, A.A., Rey, M., Coirini, H., Dauban, P., Dodd, R.H.,..., Burton, G. (2009) . Synthesis and GABAA receptor activity of 2,19-sulfamoyl analogues of allopregnanolone. Bioorganic and Medicinal Chemistry, 17(18), 6526-6533.
http://dx.doi.org/10.1016/j.bmc.2009.08.008
---------- CHICAGO ----------
Durán, F.J., Edelsztein, V.C., Ghini, A.A., Rey, M., Coirini, H., Dauban, P., et al. "Synthesis and GABAA receptor activity of 2,19-sulfamoyl analogues of allopregnanolone" . Bioorganic and Medicinal Chemistry 17, no. 18 (2009) : 6526-6533.
http://dx.doi.org/10.1016/j.bmc.2009.08.008
---------- MLA ----------
Durán, F.J., Edelsztein, V.C., Ghini, A.A., Rey, M., Coirini, H., Dauban, P., et al. "Synthesis and GABAA receptor activity of 2,19-sulfamoyl analogues of allopregnanolone" . Bioorganic and Medicinal Chemistry, vol. 17, no. 18, 2009, pp. 6526-6533.
http://dx.doi.org/10.1016/j.bmc.2009.08.008
---------- VANCOUVER ----------
Durán, F.J., Edelsztein, V.C., Ghini, A.A., Rey, M., Coirini, H., Dauban, P., et al. Synthesis and GABAA receptor activity of 2,19-sulfamoyl analogues of allopregnanolone. Bioorg. Med. Chem. 2009;17(18):6526-6533.
http://dx.doi.org/10.1016/j.bmc.2009.08.008