Prodrugs erbeta-selective substances, method for their production and pharmaceutical compounds containing these compositions

摘要

Sulfamoyl compounds (I) of 9alpha -substituted estratrienes and their pharmaceutically acceptable salts are new. Sulfamoyl compounds, of formula STEROID-Z (I), of 9alpha -substituted estratrienes and their pharmaceutically acceptable salts are new. Z : group of formula (a); n : 0-4; one of R 1>, R 2>, R 3>-SO 2NH 2 or -NHSO 2NH 2; others of R 1>, R 2>, R 3>, X, X 1>H, halo, cyano, nitro, 1-6C alkyl, C pF 2p+1, OCOR 20>, COOR 20>, OR 20>, CONHR 20> or OCONHR 21>; p : 1-3; R 20>, R 21>1-5C alkyl, 3-8C cycloalkyl, aryl, 1-4C alkylene-(aryl or 3-8C cycloalkyl) or 3-6C cycloalkylene(1-4C)alkyl, and R 20> may also be H; STEROID : group of formula (b); R 3>Z; R 16>hydroxy, tri(1-4C alkyl)silyloxy or OCOR 20>; alternatively, R 16>Z and then R 3> = hydroxy, methoxy, tri(1-4C alkyl)silyloxy or OCOR 20>; R 7>H, F, methyl or ethyl; R 9>linear or branched, optionally partly or entirely halogenated, alkyl, alkenyl or alkynyl of up to 3 C; and R 17>H or halo, and R 7>, R 16> and R 17> may be in alpha or beta positions. An independent claim is also included for the preparation of (I). [Image] ACTIVITY : Antiinfertility; Osteopathic; Cardiant; Vasotropic; Antiinflammatory; Antiarthritic; Antirheumatic; Immunosuppressive; Cytostatic; Gynecological. MECHANISM OF ACTION : Carboanhydrase (CA) inhibitor. 3-Hydroxy-9alpha -vinylestra-1,3,5(10)-trien-16alpha -yl-3-sulfamoylbenzoate showed IC50 against CAI and CAII of 3400 and 490 nM, respectively.