| 摘要 |
3,16-Dihydroxy-1,3,5(10)-estratriene derivatives (I) are new. 3,16-Dihydroxy-1,3,5(10)-estratriene derivatives of formula (I) are new: [Image] thick black line in ring = single or double bond; R 1>H, halo, OH, Me, CF 3, OMe or OEt; R 2>H, halo, OH or 1-6C optionally saturated alkoxy; R 4>H, halo, 1-10C optionally saturated alkyl, CF 3, C 2F 5or 1-6C optionally saturated alkoxy; R 7>H, halo, 1-10C optionally saturated alkyl (optionally fully or partly fluorinated), 1-6C optionally saturated alkoxy or optionally substituted aryl or heteroaryl; R 8>H, , 1-10C optionally saturated alkyl (optionally fully or partly fluorinated) or CN; R 9>H, Me, Et, CF 3or C 2F 5; R 1>1>H, ONO 2, OH, SH, halo, CH 2Cl, 1-10C optionally saturated alkyl (optionally fully or partly fluorinated), 1-6C optionally saturated alkoxy, 1-6C optionally saturated alkylthio or optionally substituted aryl or heteroaryl; R 1>3>Me, Et, CF 3or C 2F 5; R 1>4>H or 1-10C optionally saturated alkyl (optionally fully or partly fluorinated); R 1>5>H, halo or 1-10C optionally saturated alkyl (optionally fully or partly fluorinated and optionally interrupted by O, S, SO, SO 2or NR 1>5>'); R 1>5>' : H or 1-3C alkyl; R 16>optionally saturated 1-10C alkyl (optionally partly or fully fluorinated), CF 3, or pentafluoroethyl, CN or H ; R 1>7>H, OH, halo or 1-10C optionally saturated alkyl (optionally fully or partly fluorinated); or R 1>4>+R 1>5>optionally mono- or dihalogenated methylene; wavy lines = alpha or beta configuration. Excluded are: 1,3,5(10)-estratriene-3,16alpha -diol (Ia); 1,3,5(10)-estratriene-3,16beta -diol (Ib); 1,3,5(10),7-estratetraene-3,16alpha -diol (Ic); and 1,3,5(10),7-estratetraene-3,16beta -diol (Id). Independent claims are also included for the following: (1) use of compounds (I), including (Ia)-(Id), for treating diseases caused by estrogen deficiency in women and men; (2) use of the partial structure of formula (II) as a component of the total structure of compounds exhibiting a dissociation in estrogenic activity in favor of bone over uterus. [Image] ACTIVITY : Gynecological; uropathic; antiulcer; hemostatic; osteopathic; cardiant; antiarteriosclerotic; nootropic; neuroprotective; antiinflammatory; antiinfertility; immunomodulatory. MECHANISM OF ACTION : Estrogen receptor ligand. The relative binding affinity (estradiol = 100) of (Ia) for rat prostate and uterus estrogen receptors was 50 and 9 respectively, and the ratio of its relative binding affinities for human estrogen receptors alpha and beta was 6 (estradiol = 1). |
