RESUMEN
A total synthesis of 8alpha analogues of steroid estrogens with fluorine in position 2 was achieved. Structural features of these compounds were studied by the example of 17beta-acetoxy-2-fluoro-3-methoxy-8alpha-estra-1,3,5(10)-triene. It was shown that the 8alpha analogues of 2-fluorosubstituted steroid estrogens have a low uterotropic activity and retain the osteoprotective and hypocholesterolemic activities.
Asunto(s)
Estrenos/síntesis química , Estrógenos/síntesis química , Flúor , Animales , Anticolesterolemiantes/síntesis química , Anticolesterolemiantes/química , Anticolesterolemiantes/farmacología , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/síntesis química , Conservadores de la Densidad Ósea/química , Conservadores de la Densidad Ósea/farmacología , Colesterol/sangre , Estrenos/química , Estrenos/farmacología , Estrógenos/química , Estrógenos/farmacología , Femenino , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad , Útero/efectos de los fármacosRESUMEN
The study of the binding of estradiol B-nor-8-isonalogues to estrogen receptors from the rat uterus helped create the proposed model of the corresponding ligand-receptor complexes. The use of this model ensured the choice of such micromodifications in this steroid group that sharply decreased their hormonal activity. By the example of 16,16-dimethyl-D-homo-B-nor-8-isoestrone, we demonstrated the possibility of the synthesis of the estrogen analogues devoid of uterotropic activity but retaining immunosuppressive activity.