Synthesis and GABA(A) receptor activity of oxygen-bridged neurosteroid analogs.
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).
Alvarez
Lautaro D
LD
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.
Veleiro
Adriana S
AS
Baggio
Ricardo F
RF
Garland
María T
MT
Edelsztein
Valeria C
VC
Coirini
Héctor
H
Burton
Gerardo
G
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*
D011963:Receptors, GABA-A; D013256:Steroids; D010100:Oxygen