RESUMO
13-Ethyl-18-norpregn-4-ene-3, 20-dione (7) and 13-acetyl-18-norpregn-4-ene-3, 20-dione (4) were synthesized and tested in the s.c. Clauberg assay. The potencies of these compounds (1X and 1/3 X progesterone, respectively) are compared with those reported for 13-vinyl- and 13-cyanomethyl-18-norpregn-4-ene-3, 20-dione. A comparable activity (1/3 X progesterone) was found for 13-acetyl-18-norpregn-4-en-3-one (10) which lacks the 20-carbonyl group.
Assuntos
Norpregnenos/síntese química , Animais , Bioensaio , Fenômenos Químicos , Química , Feminino , Indicadores e Reagentes , Norpregnenos/farmacologia , Rotação Ocular , Progesterona/farmacologia , Relação Estrutura-AtividadeRESUMO
The structure of 16 alpha,17-epoxy-4-pregnene-3,20-dione was determined. The 20-carbonyl group eclipses the C(13)-C(17) bond. No direct correlation between the observed structure and its progestational activity could be inferred from our investigation.
Assuntos
Cetosteroides , Cristalização , Cetosteroides/farmacologia , Conformação Molecular , Congêneres da Progesterona/farmacologia , Relação Estrutura-Atividade , Difração de Raios XRESUMO
Two synthetic routes to 11 beta-chloromethylestra-1,3,5(10)-trien-3,17 beta-diol (Org 4333) are described. In biological tests this compound was found to be a potent irreversibly binding estrogen agonist.
Assuntos
Estradiol/análogos & derivados , Animais , Fenômenos Químicos , Química , Estradiol/síntese química , Estradiol/farmacologia , Feminino , Ratos , Útero/efeitos dos fármacosRESUMO
The title compound and its antipode with natural steroid configuration were synthesized and tested. Both compounds showed equal potency as anti-arrhythmic compounds. An additional effect found for the steroid with natural configuration was its plasma cholesterol lowering activity in the rat. This suggests that enantiosteroids may have a more selective action than the steroids with natural configuration.
Assuntos
Antiarrítmicos/síntese química , Estriol/análogos & derivados , Animais , Arritmias Cardíacas/tratamento farmacológico , Função Atrial , Bioensaio , Colesterol/sangue , Epitélio/efeitos dos fármacos , Estriol/síntese química , Estriol/farmacologia , Feminino , Cobaias , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Masculino , Contração Miocárdica/efeitos dos fármacos , Rotação Ocular , Ratos , Ratos Endogâmicos , Relação Estrutura-Atividade , Vagina/efeitos dos fármacosRESUMO
Using the strategy based on the Hansch method which analyses effects of substituents on biological activity in terms of their hydrophobic, electronic and steric effects we selectively synthesised a series of 11beta-substituted-17alpha-ethynyl-4-estren-17beta-ols that combine ease of synthesis with good discrimination between these factors aiming at finding the compounds with optimum biological activity in that series. The compounds were tested quantitatively in the Clauberg test (rabbit) and the ovulation inhibition test (rat). The differences in biological activity could reasonably be correlated with two steric effects introduced by the 11beta-substituent. These were a change in the overall shape of the 11beta-substituent and the angular methyl group, and direct steric hindrance of the steroid-receptor protein binding. Some exceptions were found possibly due to metabolic conversion of these compounds to the corresponding 11beta-substituted-17alpha-ethynyl-1,3,5(10)-estra-triene-3,17beta-diols.