Estrogen derivative having carriers to bone

A compound represented by the general formula (I):

• ##STR112## wherein A.sup.1 is --CO-- or --SO.sub.2 --;
• A.sup.2 is a single bond, --S--, --O--, a group of the formula --NR.sup.4 -- wherein R.sup.4 is a hydrogen atom or an alkyl group of 1 to 6 carbon atoms, or a group of the formula --CO--NR.sup.4 -- wherein R.sup.4 is as defined above;
• R.sup.1 is a hydrogen atom or an alkyl group of 1 to 6 carbon atoms;
• R.sup.2 and R.sup.3, which may be the same or different, are independently a hydrogen atom, an alkyl group of 1 to 6 carbon atoms, an alkenyl group of 3 to 6 carbon atoms, a cycloalkyl group of 3 to 7 carbon atoms, an aralkyl group, a substituted aralkyl group, a phenyl group or a substituted phenyl group, or R.sup.2 and R.sup.3, when taken together with the carbon atom to which they are bonded, form a saturated or unsaturated 3- to 7-membered alicyclic hydrocarbon group;
• k is 0 or 1 in the case of A.sup.1 being --CO--, and k is 0 in the case of A.sup.1 being --SO.sub.2 --;
• m and n are independently an integer of 0 to 5;
• Z is a group represented by any of the following general formulas (IIa) to (IIc):
• ##STR113## wherein R.sup.5 is a hydrogen atom, a halogen atom, a methyl group, a hydroxyl group or a protected hydroxyl group, and R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are independently a hydrogen atom, an alkyl group of 1 to 6 carbon atoms, a haloalkyl group of 2 to 6 carbon atoms, an allyl group, a benzyl group or a group of the formula --CH.sub.2 --O--CO--R.sup.10 wherein R.sup.10 is an alkyl group of 1 to 6 carbon atoms, ##STR114## wherein R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are as defined above, and q is 0 or 1, and ##STR115## wherein R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are as defined above;
• and E is a group of the general formula (III):
• ##STR116## wherein R.sup.12 and R .sup.13, which may be the same or different, are independently a hydrogen atom, a hydroxyl-protecting group, a group of the formula --CO--NR.sup.18 R.sup.19 wherein R.sup.18 and R.sup.19, which may be the same or different, are independently a hydrogen atom, an alkyl group of 1 to 10 carbon atoms, a hydroxyalkyl group of 2 to 6 carbon atoms, a haloalkyl group of 2 to 6 carbon atoms, a phenyl-substituted or unsubstituted carboxyalkyl group of 2 to 6 carbon atoms, a cycloalkyl group of 3 to 7 carbon atoms, an aralkyl group, a substituted aralkyl group, a phenyl group or a substituted phenyl group;
• a group of the formula --CO--R.sup.20 wherein R.sup.20 is an alkyl group of 1 to 19 carbon atoms, an alkenyl group of 3 to 19 carbon atoms, a cycloalkyl group of 3 to 7 carbon atoms, an alkyl group of 1 to 6 carbon atoms substituted by a cycloalkyl group of 3 to 7 carbon atoms, an aralkyl group, a substituted aralkyl group, a phenyl group, a substituted phenyl group, or a 5- or 6-membered hetero-cyclic group;
• or a group of the general formula (IV):
• ##STR117## wherein R.sup.21 is a hydrogen atom, a halogen atom, an alkyl group of 1 to 6 carbon atoms, or an alkoxy group of 1 to 6 carbon atoms;
• R.sup.14 and R.sup.15, which may be the same or different, are independently a hydrogen atom, a halogen atom, a methyl group, a hydroxyl group or a protected hydroxyl group;
• R.sup.16 is an alkyl group of 1 to 6 carbon atoms, a hydroxyalkyl group of 2 to 6 carbon atoms, a haloalkyl group of 2 to 6 carbon atoms, a phenyl group, or a phenyl group substituted by a hydroxyl group or a protected hydroxyl group;
• R.sup.17 is an alkyl group of 1 to 6 carbon atoms, a hydroxyalkyl group of 2 to 6 carbon atoms, or a haloalkyl group of 2 to 6 carbon atoms;
• R.sup.14 and R.sup.16, when taken together, may form --O--, --CH.sub.2 -- or --CH.sub.2 CH.sub.2 --, and R.sup.15 and R.sup.17, when taken together as --R.sup.17 --R.sup.15 --, may form --O--, --S--, --COO--, --OCO--, a group of the formula --NR.sup.22 -- wherein R.sup.22 is an alkyl group of 1 to 6 carbon atoms, a hydroxyalkyl group of 2 to 6 carbon atoms, or a haloalkyl group of 2 to 6 carbon atoms;
• a group of the formula --CHR.sup.22 --A.sup.3 -- or a group of the formula --A.sup.3 --CHR.sup.22 -- wherein R.sup.22 is as defined above, and A.sup.3 is a single bond, --O-- or --CH.sub.2 --;
• and the combination of the broken line and solid line between the carbon atoms to which R.sup.16 and R.sup.17, respectively, are bonded represents a single bond or a double bond, or a pharmaceutically acceptable salt thereof.