title: Allopregnanolone and pregnanolone analogues modified in the C ring: synthesis and activity.
abstract: (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 GABAA receptor. Their biological activity was measured by in vitro test with [(3)H]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.
authors: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic.
authors: Barbora
authors: B
authors: Slavíková
authors: Jordi
authors: J
authors: Bujons
authors: Libor
authors: L
authors: Matyáš
authors: Miguel
authors: M
authors: Vidal
authors: Zoila
authors: Z
authors: Babot
authors: Zdena
authors: Z
authors: Krištofíková
authors: Cristina
authors: C
authors: Suñol
authors: Alexander
authors: A
authors: Kasal
mesh_terms: D000818:Animals; D060326:Chemistry Techniques, Synthetic; D051379:Mice; D008958:Models, Molecular; D009474:Neurons / Q000378:metabolism; D011280:Pregnanolone / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000378:metabolism*; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D011963:Receptors, GABA-A / Q000737:chemistry / Q000378:metabolism*
chemical_list: D011963:Receptors, GABA-A; D011280:Pregnanolone