Artículo
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" (2010) European Journal of Medicinal Chemistry. 45(7):3063-3069
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Abstract:
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.
Registro:
| Documento: | Artículo |
| Título: | Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids |
| Autor: | Dansey, M.V.; Di Chenna, P.H.; Veleiro, A.S.; Krištofíková, Z.; Chodounska, H.; Kasal, A.; Burton, G. |
| Filiación: | Departamento de Química Orgánica, UMYMFOR (CONICET-FCEN), Ciudad Universitaria, C1428EGA Buenos Aires, Argentina Prague Psychiatric Centre, Ústavní 91, 181 03 Prague 8, Czech Republic Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Fleming Square 2, CZ166 10 Prague 6, Czech Republic |
| Palabras clave: | 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 |
| Año: | 2010 |
| Volumen: | 45 |
| Número: | 7 |
| Página de inicio: | 3063 |
| Página de fin: | 3069 |
| DOI: | http://dx.doi.org/10.1016/j.ejmech.2010.03.037 |
| Título revista: | European Journal of Medicinal Chemistry |
| Título revista abreviado: | Eur. J. Med. Chem. |
| ISSN: | 02235234 |
| CODEN: | EJMCA |
| CAS: | fructose, 30237-26-4, 57-48-7, 7660-25-5, 77907-44-9; sodium peroxide, 1313-60-6; tert butylbicyclophosphorothioate, 70636-86-1; hydroxide, 14280-30-9; Bicyclo Compounds, Heterocyclic; Hydroxides; Pregnenes; Receptors, GABA-A; hydroxide ion, 14280-30-9; tert-butylbicyclophosphorothionate, 70636-86-1 |
| Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02235234_v45_n7_p3063_Dansey |
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Citas:
---------- APA ----------
Dansey, M.V., Di Chenna, P.H., Veleiro, A.S., Krištofíková, Z., Chodounska, H., Kasal, A. & Burton, G. (2010) . Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids. European Journal of Medicinal Chemistry, 45(7), 3063-3069.http://dx.doi.org/10.1016/j.ejmech.2010.03.037
---------- CHICAGO ----------
Dansey, M.V., Di Chenna, P.H., Veleiro, A.S., Krištofíková, Z., Chodounska, H., Kasal, A., et al. "Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids" . European Journal of Medicinal Chemistry 45, no. 7 (2010) : 3063-3069.http://dx.doi.org/10.1016/j.ejmech.2010.03.037
---------- MLA ----------
Dansey, M.V., Di Chenna, P.H., Veleiro, A.S., Krištofíková, Z., Chodounska, H., Kasal, A., et al. "Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids" . European Journal of Medicinal Chemistry, vol. 45, no. 7, 2010, pp. 3063-3069.http://dx.doi.org/10.1016/j.ejmech.2010.03.037
---------- VANCOUVER ----------
Dansey, M.V., Di Chenna, P.H., Veleiro, A.S., Krištofíková, Z., Chodounska, H., Kasal, A., et al. Synthesis and GABAA receptor activity of A-homo analogues of neuroactive steroids. Eur. J. Med. Chem. 2010;45(7):3063-3069.http://dx.doi.org/10.1016/j.ejmech.2010.03.037
