Assuntos
Noresteroides/metabolismo , Tecido Adiposo/metabolismo , Animais , Hidrólise , Técnicas In Vitro , Intestino Delgado/metabolismo , Rim/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Linestrenol/análogos & derivados , Linestrenol/metabolismo , Músculos/metabolismo , Miocárdio/metabolismo , Noretindrona/análogos & derivados , Noretindrona/metabolismo , Acetato de Noretindrona , Norgestrel/análogos & derivados , Norgestrel/metabolismo , CoelhosAssuntos
Anticoncepcionais Orais Combinados/farmacologia , Anticoncepcionais Orais Sintéticos/farmacologia , Anticoncepcionais Orais/farmacologia , Lipase Lipoproteica/sangue , Tecido Adiposo/enzimologia , Animais , Quilomícrons/metabolismo , Ativação Enzimática/efeitos dos fármacos , Feminino , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Lipoproteínas VLDL/sangue , Linestrenol/análogos & derivados , Linestrenol/farmacologia , Mestranol/farmacologia , Ratos , Triglicerídeos/metabolismoRESUMO
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.