Patent DE-19954105-A1 (DE)
Title: Treatment of estrogen deficiency-associated conditions, e.g. menopausal syndrome, osteoporosis, infertility or prostatic hypertrophy, using new or known gonatrienes having tissue-selective estrogenic activity
Inventor: HILLISCH ALEXANDER
IPC: C07J1/00
Filed: 1999-11-02
Abstract: The use of 19-nor-steroids (1,3,5(10)-gonatrienes) (I) is claimed for the treatment of diseases and conditions associated with estrogen deficiency in females or males.  The use of 19-nor-steroids of formula (I) is claimed for the treatment of diseases and conditions associated with estrogen deficiency in females or males: R1 = halo, R18, or OR18; R18 = H, optionally unsaturated 1-6C hydrocarbyl or CF3; R2 = R18, OR18 or OSO2R19; R19 = NR20R21, 4-6C polymethyleneimino or morpholino; R20, R21 = H, 1-5C alkyl or COR22; R22 = 1-12C hydrocarbyl (optionally containing 1-3 double and/or triple bonds), 3-7C cycloalkyl, aryl or a combination of these units; R3 = OR'18 OSO2R19 or OCOR22; R'18 = as R18 or aryl, heteroaryl or aralkyl; R6, R7 = H, halo, OR18, OSO2R19, R22, optionally unsaturated partially or completely halogenated 1-10C alkyl or (all optionally substituted) aryl, heteroaryl or aralkyl; R8, R9 = H, optionally unsaturated partially or completely halogenated 1-10C alkyl, XR18, halo, CN or SCN; X = O or S; R11 = H, halo, OR18, OSO2R19, R22, XR18, ONO2, optionally unsaturated partially or completely halogenated 1-10C alkyl or (all optionally substituted) aryl, heteroaryl or aralkyl; and R'11 = H; or R11+ R'11 = CH 2; R14 = H, 1-3C alkyl, 2-3C alkenyl or 2-3C alkynyl; and R15 = H; or R14 + R15 = optionally mono- or dihalogenated =CH2; R'15, R16 = H, halo, OR18, OSO2R19 or R22; R17/R'17 = H/halo; H/OSO2R19; R18/COR22; R18/OCOR22;  OR18/R18; or OR18/OCOR22; or R17 + R'17 = CR23R24 or O; and R23, R24 = H or halo. (I) optionally contains one or more double bond(s) in the 6(7), 7(8), 9(11), 11(12), 14(15) and/or 15(16) position(s).  Independent claims are included for: (A) the use of a gonatriene partial structure of formula (II) or (II') as a component of the overall structure of compounds showing dissociation between their estrogenic activity on bones and that on the uterus; and (B) as new compounds, with the exception of (I) where:  (i) (i) the 13-H has  beta -configuration and the following substituents are present (where unspecified substituents are H and double bonds are present only if specifically mentioned):  (a) 3-isopropoxycarbonyl and 17-oxo;  (b) 3-OAc and 17-oxo, 17 alpha -OH, 17 beta -OH, 17 alpha -OAc or 17 beta -OAc; (c) 3-OH and 17-oxo, 17 alpha -OH, 17 beta -OH, 17 alpha -OVal, 17 beta -OVal, 17 alpha -OAc or 17 beta -OAc; (d) 3-OMe and 17 beta -OH (optionally together with 9 alpha -OH, 9 beta -OH, 9 alpha -OMe or 9 OMICRON Me), 17-oxo (optionally together with a combination of 15-OMe/H plus 9(11) and 15(16) double bonds), 17 beta -Ac (optionally together with 16 alpha -OH, 16 beta -OH or 8(9) and 14(15) double bonds) or 17 alpha -Ac together with 16 alpha -OH or 16 beta -OH; (e) 3-O-n-Bu and 17-oxo, 17 alpha -OH, 17 beta -OH or 17-Ac together with a 16(17) double bond; or (f) 3-Val (Val = valerate) and 17 alpha -Val, 17 beta -Val, 17 alpha -OH or 17 beta -OH; or  (ii) the 13-H has  alpha -configuration and the following substituents are present: (a) 3-OAc and 17-oxo; (b) 3-OH and 17-oxo; (c) 3-OMe and 17-oxo (optionally together with a 9(11) double bond or with a combination of 15-OMe/H plus 9(11) and 15(16) double bonds), 17 alpha -OH, 17-p-chlorobenzoate, 17 beta -OH, 17 beta -OAc, 17 alpha -OAc or 17 alpha -OH/17 beta -Me together with 16 alpha -OH; or (d) 3-O-n-Bu and 17-oxo, 17- alpha -OH or 17 beta -OH.