New 8-beta-substituted estratriene derivatives esterified with a sulfamoylphenyl-substituted acid residue, are prodrugs useful as carboanhydrase inhibitors for treating estrogen deficiency disorders

摘要

Sulfamoyl compounds (I) of 8beta -substituted estratrienes and their pharmaceutically acceptable salts are new. Sulfamoyl compounds, of formula STEROID-Z (I), of 8beta -substituted estratrienes and their pharmaceutically acceptable salts are new. Z : grop 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 31>group Z shown above; R 17>hydroxy, tri(1-4C alkyl)silyloxy or OCOR 20>; alternatively, R 17>Z and then R 31> = hydroxy, methoxy, tri(1-4C alkyl)silyloxy or OCOR 20>; R 8>linear or branched, optionally partly or entirely halogenated, alkyl, alkenyl or alkynyl of up to 3 C; and R 16>H, halo or Me, and 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-8'beta -vinylestra-1',3',5'(10')-trien-17'beta -yl)-3-sulfamoylbenzoate (Ia) showed IC50 against CAI and CAII of 3900 and 570 nM, respectively.