title: Synthesis and GABA(A) receptor activity of oxygen-bridged neurosteroid analogs.
abstract: 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 3alpha-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-[(3)H]butylbicycloorthobenzoate as radiolabeled ligand for the GABA(A) receptor. The activity of compound 4 was similar to that of allopregnanolone (1). 1alpha,11alpha-Epoxypregnanolone (6) was more active than pregnanolone (2).
authors.affiliation: 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.
authors.forename: Lautaro D
authors.initials: LD
authors.lastname: Alvarez
authors.forename: Adriana S
authors.initials: AS
authors.lastname: Veleiro
authors.forename: Ricardo F
authors.initials: RF
authors.lastname: Baggio
authors.forename: María T
authors.initials: MT
authors.lastname: Garland
authors.forename: Valeria C
authors.initials: VC
authors.lastname: Edelsztein
authors.forename: Héctor
authors.initials: H
authors.lastname: Coirini
authors.forename: Gerardo
authors.initials: G
authors.lastname: Burton
mesh_terms: D000818:Animals; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects*; D010100:Oxygen / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D011963:Receptors, GABA-A; D013256:Steroids; D010100:Oxygen