Studies On Synthesis And Hormonal Properties Of Asoprisnil

Aim To prepare asoprisnil and optimize its synthetic process, and studies on its progestagenic, estrogenic, glucocorticoid, androgenic and anabolic agonist or antagonist properties.Method Starting from 3,3-[1,2-ethanediylbis(oxy)]estra-△5(10),9(11)-diene-17-one, asoprisnil and another 2 derivatives had been prepared via 5α,10α-epoxidation, 11β-aryl substituted, 17β-epoxidation, 17-ring opening, 17α-methylation, 17β-methylation, hydration, oximation and so on. All structures of intermediates and three target compounds were verified by UV, IR, MS, 1H-NMR and 13C-NMR. Progestagenic, estrogenic, glucocorticoid, androgenic and anabolic agonistic and antagonistic properties were assessed by rabbit endometrial transformation model, mouse uterine wet weight, rat thymus weight, the weight of levator ani muscle.Result Asoprisnil and another 2 derivatives were synthesized. Structures of intermediates and three target compounds were confirmed by UV, IR, MS, 1H-NMR and 13C-NMR. McPhail scores indicated that asoprisnil was a potent selective progesterone receptor modulator, it was an antagonist in presence of progesterone and agonist in absence of progesterone, albeit weaker than mifepristone and progesterone, its strength were a dose-dependant. Weak anti-estrogenic, anti-glucocorticoid, anti-androgenic activities could only be seen at high doses. Asoprisnil didn't exhibit conspicuous estrogenic, glucocorticoid, androgenic agonist and anabolic agonist or antagonist properties at thearapeutic doses in animal experiments.Conclusion Compared to the literature, the optimized route had simplified reaction condition, improved the overall yield and satisfied the requirement of industry exploitation. Results showed asoprisnil had partial agonism- antagonism. But it didn't exhibit conscious estrogenic, glucocorticoid, androgenic agonist and anabolic agonist or antagonist properties. Asoprisnil had great clinical thearapeutic potential in gynecological diseases.