17?-ALKYL-17?-OXY-ESTRATRIENES AND INTERMEDIATES FOR THE PRODUCTION THEREOF, AND USE OF SAID 17?-ALKYL-17?-OXY-ESTRATRIENES FOR PRODUCING MEDICAMENTS AND PHARMACEUTICAL PREPARATIONS

摘要

17alpha -Alkyl-11beta -halo-17beta -oxy-estratriene derivatives (I), having a 7alpha -side-chain, are new. 17alpha -Alkyl-11beta -halo-17beta -oxy-estratriene derivatives of formula (I), their acid addition salts and esters are new. [Image] Hal : F or Cl; R 3H, 1-4C alkyl, 1-4C alkanoyl or 3-7C cyclic ether residue; R 17'H, 1-4C alkyl or 1-4C alkanoyl; R 17''1-4C alkyl (optionally partially fluorinated) or 2-4C alkynyl; Q : -U-V-W-X-Y-Z-E; U : 1-13C alkylene, 2-13C alkenylene, 2-13C alkynylene, -A-B- or -A-O-B-; A : benzylidene (bonded to the steroid structure via CH 2), phenyl or (1-3C) alkyl-aryl (bonded to the steroid structure via alkyl); B : 1-13C alkylene, 2-13C alkenylene or 2-13C alkynylene; V : CH 2or CO; W : N(R 6) or N +(O -)(R 6); or an azolidinylene or azolidinylene-N-oxide ring (where X is incorporated into the ring); R 6H, CH 2R 7or COR 7; R 7H; 1-14C alkylene, 2-14C alkenylene or 2-14C alkynylene (all optionally at least partially fluorinated, optionally mono- or polyhydroxylated and optionally interrupted by 1-3 of O, S, NH or N(1-3C alkyl)); or aryl, heteroaryl, 3-10C cycloalkyl, 4-15C cycloalkylalkyl, 7-20C aralkyl, heteroaryl-(1-6C) alkyl, aminoalkyl or biphenylyl (all optionally substituted); X : 1-12C alkylene, 2-12C alkenylene or 2-12C alkynylene; Y : direct bond, R 11, OR 11, CH=CF or NHCONHR 12; R 10direct bond, 1-6C alkylene, 2-6C alkenylene or 2-6C alkynylene; R 111-5C alkylene, 2-5C alkenylene or 2-5C alkynylene; or aryl, heteroaryl, 3-10C cycloalkyl, 4-15C cycloalkylalkyl or 7-20C aralkyl (all optionally substituted); R 12optionally substituted arylene (bonded to Z); Z : direct bond; or 1-9C alkylene, 2-9C alkenylene or 2-9C alkynylene (all optionally partially or completely fluorinated); and E : CF 3or at least partially fluorinated aryl. Provided that if Y is SR 10, SOR 10or SO 2R 10if W is N +(O -)(R 6) or azolidinylene-N-oxide ring. Independent claims are also included for: (1) 17beta -oxy-estratriene and 17-oxo-estratriene derivatives of formula (II); and (2) 17beta -oxy-estratriene and 17-oxo-estratriene derivatives of formula (III). [Image] W : N +(O -)(R 6) or azolidinylene-N-oxide. ACTIVITY : Cytostatic; Antiinfertility; Gynecological; Antialopecia; Depilatory. MECHANISM OF ACTION : Estrogen antagonist. In antiuterotrophic tests in rats, (5-(11beta -fluoro-3,17beta -dihydroxy-17alpha -methyl-estra-1,3,5(10)-trien-7alpha -yl)-pentyl)-(methyl)-(7,7,8,8,9,9,9-heptafluorononyl)-amine (Ia) at a dose of 0.03 mg/kg s.c. gave 94% of the uterotrophic effect of estradiol benzoate.