Estrogen nucleus derivatives for use in the inhibition of sex steroid activity

A sex steroid activity inhibiting compound having, as part of its molecular structure, a substituted or unsubstituted estrogenic nucleus of structure I:

• ##STR59## wherein the dotted lines represent optional pi bonds and wherein said compound includes as another part of its molecular structure a side chain substituents onto a ring carbon of said general structure I represented by the formula --R.sup.1 [--B--R.sup.2 --].sub.x L--G wherein at least one of said side chains is substituted at carbon 16 wherein:
• x is an integer from 0 to 6, wherein at least one of L and G is polar moiety distanced from said ring carbon by at least three intervening atoms, and wherein:
• R.sup.1 and R.sup.2 are independently either absent or selected from the group consisting of straight- or branched-chain alkylene, straight- or branched-chain alkynylene, straight- or branched-chain alkenylene, phenylene, and fluoro-substituted analogs of the foregoing;
• B is either absent or selected from the group consisting of --O--, and phenylene (R.sup.3 being hydrogen or lower alkyl);
• L is either a moiety which together with G, forms a heterocyclic ring having at least one nitrogen atom or is selected from the group consisting of lower alkyl, --CONR.sup.4 --, --CSNR.sup.4 --, --NR.sup.5 CO--, --NR.sup.5 CS--, --NR.sup.5 CONR.sup.4 -- --NR.sup.5 SO.sub.2 --, --NR.sup.4 --, --S--, --SO-- and --SO.sub.2 -- (R.sup.4 and R.sup.5 being independently selected from the group consisting of hydrogen and lower alkyl;
• and
• G is either a moiety which together with L forms a heterocyclic ring having at least one nitrogen atom or is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl, (C.sub.3 -C.sub.7)cycloalkyl, bromo(lower)alkyl, chloro(lower)alkyl, fluoro(lower)alkyl, iodo(lower)alkyl, cyano(lower)alkyl, carboxy(lower)alkyl, (lower)alkoxycarbonyl(lower)alkyl, (C.sub.6 -C.sub.10)aryl, (C.sub.7 -C.sub.11)arylalkyl, di(lower)alkylamino(lower)alkyl, fluoro-substituted analogs of the foregoing.

A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically effective amount of a sex steroid activity inhibitor having, as part of its molecular structure, a substituted or unsubstituted nucleus selected from the group consisting of:

• ##STR63## wherein said compound includes as another part of its molecular structure a side chain substitution of the formula --R.sup.1 [--B--R.sup.2 --].sub.x L--G wherein:
• x is an integer from 0 to 6, wherein at least one of L and G is a polar moiety distanced from said ring carbon by at least three intervening atoms, and wherein:
• R.sup.1 and R.sup.2 are independently either absent or selected form the group consisting of straight- or branched-chain alkylene, straight- or branched-chain alkynylene, straight-or branched-chain alkenylene, phenylene, and fluoro-substituted analogs of the foregoing;
• B is either absent or selected from the group consisting of --O--, --CR.sup.3 OR.sup.3 --, and phenylene (R.sup.3 being hydrogen or lower alkyl);
• L is selected from the group consisting of lower alkyl, --CONR.sup.4 --, --CSNR.sup.4 --, --NR.sup.5 CO--, --NR.sup.5 CS--, --NR.sup.5 CONR.sup.4 --, --O--, --NR.sup.4 --, --S--, --SO-- and --SO.sub.2 -- and a derivative of the foregoing which, together with G, forms a 5-7 membered nitrogen hetero ring (R.sup.4 and R.sup.5 being independently selected from the group consisting of hydrogen, lower alkyl;
• and R.sup.6 being selected from the group consisting of hydrogen, nitrile and nitro);
• and
• G is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl, (C.sub.3 -C.sub.7)cycloalkyl, bromo(lower)alkyl, chloro(lower)alkyl, fluoro(lower)alkyl, iodo(lower)alkyl, cyano(lower)alkyl, carboxy(lower)alkyl, (lower)alkoxycarbonyl(lower)alkyl, (C.sub.6 -C.sub.10)aryl, (C.sub.7 -C.sub.11)arylalkyl, di(lower)alkylamino(lower)alkyl, fluoro-substituted analogs of the foregoing, and a derivative of the foregoing which, together with L, form a 5-7 membered nitrogen hetero ring.

A sex steroid inhibiting compound having, as part of its molecular structure, a substituted or unsubstituted nucleus selected from the group consisting of:

• ##STR64## wherein said compound includes as another part of its molecular structure a side chain substitution of the formula --R.sup.1 [--B--R.sup.2 --].sub.x L--G wherein:
• x is an integer from 0 to 6, wherein at least one of L and G is a polar moiety distanced from said ring carbon by at least three intervening atoms, and wherein:
• R.sup.1 and R.sup.2 are independently either absent or selected form the group consisting of straight- or branched-chain alkylene, straight- or branched-chain alkynylene, straight-or branched-chain alkenylene, phenylene, and fluoro-substituted analogs of the foregoing:
• B is either absent or selected from the group consisting of --O--, --CR.sup.3 OR.sup.3 --, and phenylene (R.sup.3 being hydrogen or lower alkyl);
• L is selected from the group consisting of lower alkyl, --CONR.sup.4 --, --CSNR.sup.4 --, --NR.sup.5 CO--, --NR.sup.5 CS--, --NR.sup.5 CONR.sup.4 --, --SO.sub.2 NR.sup.4 --, --O--, --NR.sup.4 --, --S--, --SO-- --SO.sub.2, and a derivative of the foregoing which, together with G, forms a 5-7 membered nitrogen hetero ring-(R.sup.4 and R.sup.5 being independently selected from the group consisting of hydrogen and lower alkyl;
• and R.sup.6 being selected from the group consisting of hydrogen, nitrile and nitro);
• and
• G is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl, (C.sub.3 -C.sub.7)cycloalkyl, bromo(lower)alkyl, chloro(lower)alkyl, fluoro(lower)alkyl, iodo(lower)alkyl, cyano(lower)alkyl, carboxy(lower)alkyl, (lower)alkoxycarbonyl(lower)alkyl, (C.sub.6 -C.sub.10)aryl, (C.sub.7 -C.sub.11)arylalkyl, di(lower)alkylamino(lower)alkyl, fluoro-substituted analogs of the foregoing, and a derivative of the foregoing which forms a 5-7 membered nitrogen hetero ring.