565-95-7Relevant academic research and scientific papers
Synthesis of new steroidal inhibitors of P-glycoprotein-mediated multidrug resistance and biological evaluation on K562/R7 erythroleukemia cells
De Ravel, Marc Rolland,Alameh, Ghina,Melikian, Maxime,Mahiout, Zahia,Emptoz-Bonneton, Agnès,Matera, Eva-Laure,Lomberget, Thierry,Barret, Roland,Rocheblave, Luc,Walchshofer, Nadia,Beltran, Sonia,El Jawad, Lucienne,Mappus, Elisabeth,Grenot, Catherine,Pugeat, Michel,Dumontet, Charles,Le Borgne, Marc,Cuilleron, Claude Yves
supporting information, p. 1832 - 1845 (2015/04/21)
A simple route for improving the potency of progesterone as a modulator of P-gp-mediated multidrug resistance was established by esterification or etherification of hydroxylated 5α/β-pregnane-3,20-dione or 5β-cholan-3-one precursors. X-ray crystallography of representative 7α-, 11α-, and 17α-(2′R/S)-O-tetrahydropyranyl ether diastereoisomers revealed different combinations of axial-equatorial configurations of the anomeric oxygen. Substantial stimulation of accumulation and chemosensitization was observed on K562/R7 erythroleukemia cells resistant to doxorubicin, especially using 7α,11α-O-disubstituted derivatives of 5α/β-pregnane-3,20-dione, among which the 5β-H-7α-benzoyloxy-11α-(2′R)-O-tetrahydropyranyl ether 22a revealed promising properties (accumulation index 2.9, IC50 0.5 μM versus 1.2 and 10.6 μM for progesterone), slightly overcoming those of verapamil and cyclosporin A. Several 7α,12α-O-disubstituted derivatives of 5β-cholan-3-one proved even more active, especially the 7α-O-methoxymethyl-12α-benzoate 56 (accumulation index 3.8, IC50 0.2 μM). The panel of modulating effects from different O-substitutions at a same position suggests a structural influence of the substituent completing a simple protection against stimulating effects of hydroxyl groups on P-gp-mediated transport.
Allopregnanolone and pregnanolone analogues modified in the C ring: Synthesis and activity
Slavíková, Barbora,Bujons, Jordi,Matyá?, Libor,Vidal, Miguel,Babot, Zoila,Kri?tofíková, Zdena,Su?ol, Cristina,Kasal, Alexander
, p. 2323 - 2336 (2013/06/04)
(25R)-3β-Hydroxy-5α-spirostan-12-one (hecogenin) and 11α-hydroxypregn-4-ene-3,20-dione (11α-hydroxyprogesterone) were used as starting materials for the synthesis of a series of 11- and 12-substituted derivatives of 5ξ-pregnanolone (3α-hydroxy-5α- pregnan-20-one and 3α-hydroxy-5β-pregnan-20-one), the principal neurosteroid acting via γ-aminobutyric acid (GABA). These analogues were designed to study the structural requirements of the corresponding GABA A receptor. Their biological activity was measured by in vitro test with [3H]flunitrazepam as radioligand in which allopregnanolone and its active analogues stimulated the binding to the GABAA receptor. Analysis of the SAR data suggests dependence of the flunitrazepam binding activity on the hydrophobic-hydrophilic balance of the groups at the C-ring edge rather than on specific interactions between them and the receptor.
Synthesis of deuterium labeled NMDA receptor inhibitor - 20-Oxo-5β-[9,12,12-2H3]pregnan-3α-yl-l- glutamyl 1-ester
Kapras, Vojtech,Slavickova, Alena,Stastna, Eva,Vyklicky Jr., Ladislav,Vales, Karel,Chodounska, Hana
experimental part, p. 282 - 287 (2012/03/26)
20-Oxo-5β-[9,12,12-2H3]pregnan-3α-yl-l- glutamyl 1-ester 11 was synthesized as an internal standard for quantification of a neuroprotective NMDA receptor ligand, 20-oxo-5β-pregnan-3α-yl-l- glutamyl 1-ester 18 and its metabolites, in
NEW STEROID INHIBITORS OF PGP FOR USE FOR INHIBITING MULTIDRUG RESISTANCE
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Page/Page column 23, (2011/07/07)
The present invention relates to a compound of formula (I) for its use for reversing or inhibiting multidrug resistance.
Synthesis and GABAA receptor activity of oxygen-bridged neurosteroid analogs
Alvarez, Lautaro D.,Veleiro, Adriana S.,Baggio, Ricardo F.,Garland, Maria T.,Edelsztein, Valeria C.,Coirini, Hector,Burton, Gerardo
, p. 3831 - 3838 (2008/09/21)
Three analogs of neuroactive steroids were prepared (4-6) in which 1,11- or 11,19-oxygen bridges give a constrained conformation. Their 3D structures were obtained by ab initio calculations and in the case of 3α-hydroxy-11,19-epoxypregn-4-ene-20-one (4), confirmed by X-ray analysis. Biological activity of the synthetic steroids was assayed in vitro using t-[3H]butylbicycloorthobenzoate as radiolabeled ligand for the GABAA receptor. The activity of compound 4 was similar to that of allopregnanolone (1). 1α,11α-Epoxypregnanolone (6) was more active than pregnanolone (2).
