Novel beta-hydroxyketones and beta-alkoxyketones with estrogenic activity

Compounds of the formula (I)

• or stereoisomers, pharmaceutically acceptable salts or prodrug forms thereof, wherein
• x is an integer from 0 to 3 and y is an integer from 0 to 2, provided that x and y do not have the same value;
• R1 and R2 are the same or different phenyl or naphthyl groups of the formula
• and are substituted with 0-5 R5 or R6;
• R5 or R6 are the same or different and are selected from hydrogen, lower alkyl, lower alkoxyl, halogen, nitro, amino or hydroxyl;
• R3 is selected from hydrogen or C1-4alkyl;
• R4 is selected from hydrogen or methyl;
• provided that
• when the compound has the formula (I) and x is 0, y is 1, R3 is hydrogen and R4 is hydrogen, then R1 cannot be an unsubstituted phenyl, 2-hydroxyphenyl or 3-methoxyphenyl if R2 is unsubstituted phenyl, and then R1 cannot be 4-chlorophenyl if R2 also is 4-chlorophenyl [a)-d)], and
• when the compound has the formula (I) and x is 0, y is 2, R3 is hydrogen and R4 is hydrogen, then R1 cannot be an unsubstituted phenyl, 2-hydroxyphenyl, 4-hydroxyphenyl, 4-methoxyphenyl, 3-nitrophenyl, 4-chlorophenyl or naphthalen-2-yl, if R2 is an unsubstituted phenyl, [e)-h)] and
• when the compound has the formula (I) and x is 1, y is 0, R3 is hydrogen and R4 is hydrogen, then R1 cannot be an unsubstituted phenyl or 3-fluorophenyl if R2 is unsubstituted phenyl, and then R1 cannot be an unsubstituted phenyl or 3,4-dimethoxyphenyl if R2 is 4-methoxyphenyl, and then R1 cannot be 2-chlorophenyl if R2 is 2-chlorophenyl, [i)-1)] and
• when the compound has the formula (I) and x is 2, y is 0, and R4 is hydrogen, then R3 cannot be hydrogen if R1 is an unsubstituted phenyl and R2 is an unsubstituted phenyl or 4-nitrophenyl, or if R1 is 4-hydroxy-3-methoxyphenyl and R2 is an unsubstituted phenyl or 4-hydroxy-3-methoxyphenyl, and then R3 cannot be methyl, if R1 and R2 are simultaneously unsubstituted phenyls, [m)-q)] and
• when the compound has the formula (I) and x is 2, y is 1, R3 is hydrogen and R4 is hydrogen, then R1 cannot be an unsubstituted phenyl if R2 also is an unsubstituted phenyl [r)], and
• when the compound has formula (I) and x is 3, y is 0, R3 is hydrogen or methyl and R4 is hydrogen, then R1 cannot be an unsubstituted phenyl if R2 also is an unsubstituted phenyl, [s)-t)] and
• when the compound has the formula (I) and x is 0, y is 1 or 2, R3 is hydrogen and R4 is methyl, then R1 cannot be an unsubstituted phenyl if R2 also is an unsubstituted phenyl [u)-v)].

A compound selected from the group consisting of

• 5-hydroxy-1-(4-hydroxy-phenyl)-5-phenyl-hexan-3-one (23),
• 5-hydroxy-6-(4-hydroxy-phenyl)-1-phenyl-hexan-3-one (25),
• 5-hydroxy-1-(4-hydroxy-phenyl)-6-phenyl-hexan-3-one (31),
• 1-hydroxy-6-(4-hydroxy-phenyl)-1-phenyl-hexan-3-one (34),
• 1-hydroxy-1-(3-hydroxy-phenyl)-6-(4-hydroxy-phenyl)-hexan-3-one (35),
• 6-hydroxy-1,6-diphenyl-heptan-4-one (36),
• 6-hydroxy-1-(4-hydroxy-phenyl)-6-phenyl-heptan-4-one (37),
• 2-hydroxy-7-(4-hydroxy-phenyl)-1-phenyl-heptan-4-one (40),
• 5-methoxy-6-(4-fluorophenyl)-1-phenyl-hexan-3-one (48),
• 5-methoxy-6-naphthalen-2-yl-1-phenyl-hexan-3-one (50),
• 2-methoxy-1,7-diphenyl-heptan-4-one (51),
• and stereoisomers, pharmaceutically acceptable salts and prodrug forms thereof.

Compounds of the formula (I)

• or stereoisomers, pharmaceutically acceptable salts or prodrug forms thereof, wherein
• x is an integer from 0 to 3 and y is an integer from 0 to 2, provided that x and y do not have the same value;
• R1 and R2 are the same or different phenyl or naphthyl groups of the formula
• and are substituted with 0-5 R5 or R6;
• R5 or R6 are the same or different and are selected from hydrogen, lower alkyl, lower alkoxyl, halogen, nitro, amino or hydroxyl;
• R3 is selected from hydrogen or C1-4alkyl;
• R4 is selected from hydrogen or methyl,
• for use as pharmaceuticals.

A pharmaceutical composition comprising a compound of the formula (I)

• or a stereoisomer, pharmaceutically acceptable salt or a prodrug form thereof;
• wherein
• x is an integer from 0 to 3 and y is an integer from 0 to 2, provided that x and y do not have the same value;
• R1 and R2 are the same or different phenyl or naphthyl groups of the formula
• and are substituted with 0-5 R5 or R6;
• R5 or R6 are the same or different and are selected from hydrogen, lower alkyl, lower alkoxyl, halogen, nitro, amino or hydroxyl;
• R3 is selected from hydrogen or C1-4alkyl;
• R4 is selected from hydrogen or methyl;
• in association with a pharmaceutically acceptable carrier.