RU2007112114A - APPLICATION OF A SELECTIVE MODULATOR OF ESTROGEN RECIPES TO PRODUCE A PHARMACEUTICAL DRUG FOR USE IN THE METHOD OF TREATMENT OR PREVENTION OF ANDROGENIC INSUFFICIENCY - Google Patents

Claims (13)

1. The use of a selective modulator of estrogen receptors or an isomer thereof, a mixture of isomers, a metabolite or a pharmaceutically acceptable salt, for the manufacture of a pharmaceutical preparation for use in a method for the treatment or prevention of androgen deficiency in a male individual. 2. The use according to claim 1, where the selective modulator of estrogen receptors is a triphenylalkane compound, a triphenylalkene compound, where the alkene chain is a halogen substituted butene or propene, benzothiophene compound, EM652, EM800, EM776, EM651, EM312, ICI 182780, ERA- 923, zindoxifene, deacetylated zindoxifene, ZK119010, TSE-4247, lazoxifen, lazoxifen analog, nafoxidine, bazedoxifene, GW5638, GW7604, ICI 164384, RU 58668, RU 39411 or EM 319, or an isomer thereof, a pharmaceutically acceptable salt thereof, isomeric mixture. 3. The use according to claim 2, where the selective modulator of estrogen receptors is a triphenylbutene compound of the formula (I)

where R1 represents H, halogen, OCH ₃ or OH; and R2 is a)

where X represents O, NH or S; and n is an integer from 1 to 4; and R4 and R5, which are the same or different, are alkyl with a carbon number of 1 to 4, H, —CH ₂ C or —CH ₂ CH ₂ OH; or R4 and R5 form N a five- or six-membered ring or a heteroaromatic ring; or b) -Y- (CH ₂ ) _n CH ₂ -O-R6 where Y represents O, NH or S, and n is an integer from 1 to 4; and R6 is H, —CH ₂ CH ₂ OH or —CH ₂ CH ₂ Cl; or c) 2,3-dihydroxypropoxy, 2-methylthioethoxy, 2-chloroethoxy, 1-ethyl-2-hydroxyethoxy, 2,2-diethyl-2-hydroxyethoxy or carboxymethoxy; and R3 is H, halogen, OH or —OCH ₃ or an isomer thereof, a mixture of isomers, a metabolite or a pharmaceutical salt. 4. The use according to claim 2, where the selective modulator of estrogen receptors is a triphenylbutene compound of the formula (I)

where R1 represents H, halogen, OCH ₃ or OH; and R2 is a)

where i) X represents NH or S; and n is an integer from 1 to 4; and R4 and R5, which are the same or different, are alkyl with a carbon number of 1 to 4, H, —CH ₂ C or —CH ₂ CH ₂ OH; or R4 and R5 form N a five- or six-membered ring or a heteroaromatic ring; or where ii) X represents O, and n is an integer from 1 to 4; and one of R4 and R5 is —CH ₂ CCH or —CH ₂ CH ₂ OH, and the other is H or C ₁ -C ₄ alkyl; or R4 and R5 form an imidazole ring containing an N six-membered ring or a heteroaromatic ring; or R2 is b) -Y- (CH ₂ ) _n CH ₂ -O-R6 where Y represents O, NH or S, and n represents an integer from 1 to 4; and R6 is H, —CH ₂ CH ₂ OH or —CH ₂ CH ₂ Cl; or R2 is c) 2,3-dihydroxypropoxy, 2-methylthioethoxy, 2-chloroethoxy, 1-ethyl-2-hydroxyethoxy, 2,2-diethyl-2-hydroxyethoxy or carboxymethoxy; and R3 is H, halogen, OH or —OCH ₃ or an isomer thereof, a mixture of isomers, a metabolite or a pharmaceutical salt. 5. The use according to any one of the above paragraphs, where the selective modulator of estrogen receptors is a compound with tissue-specific antiestrogenic or estrogenic effects suitable for male individuals. 6. The use according to claim 5, where the selective modulator of estrogen receptors is selected from the group consisting of (Z) -2- [3- (4-chloro-1,2-diphenylbut-1-enyl) phenoxy] ethanol, (Z) -2- {2- [4- (4-chloro-1,2-diphenylbut-1-enyl) phenoxy] ethoxy} ethanol (fispemifene), (Z) - {2- [3- (4-chloro-1,2-diphenylbut-1-enyl) phenoxy] ethyl} dimethylamine, (E) -3- {4-chloro-1- [4- (2-hydroxyethoxy) phenyl] -2-phenylbut-1-enyl} phenol, (E) -3- {4-chloro-1- [4- (2-imidazol-1-ylethoxy) phenyl] -2-phenylbut-1-enyl} phenol, (Z) -3- {4-chloro-1- [4- (2-imidazol-1-ylethoxy) phenyl] -2-phenylbut-1-enyl} phenol and (Z) -2- [4- (4-chloro-1,2-diphenylbut-1-enyl) phenoxy] ethanol (ospemifene) or an isomer thereof, a mixture of isomers, a metabolite or a pharmaceutically acceptable salt. 7. The use according to claim 6, where the selective modulator of estrogen receptors is fispemifen or its metabolite or a pharmaceutically acceptable salt. 8. The use of a selective modulator of estrogen receptors, as defined in any one of claims 1 to 7, or an isomer thereof, a mixture of isomers, a metabolite or a pharmaceutically acceptable salt for the manufacture of a pharmaceutical preparation that can be used to prevent or treat a disease or disorder in a male individual where said disease or disorder in said individual is caused by androgen deficiency. 9. The use of claim 8, where the specified disease or disorder is selected from the group consisting of hypogonadism, in particular, but not limited to secondary hypogonadism resulting from a disease or disorder, such as Kallman syndrome, Prader-Labhart-Willi syndrome, Lawrence-Moon-Beadle syndrome, pituitary insufficiency / adenomas, Pascvalini syndrome, hemochromatosis, hyperprolactinemia, damage pituitary-hypothalamic system due to tumors, trauma, radiation, obesity, chronic diseases such as diabetes mellitus, hypothyroidism or another disease or disorder that may affect central gonadotropin products; age-related testosterone deficiency and the resulting diseases or disorders, such as decreased muscle strength, sexual dysfunction, decreased libido, loss of muscle mass, decreased bone density, depressed mood and decreased cognitive function; and any muscle atrophy / dystrophy; lipodystrophy; long-term serious illness; sarcopenia; weakness or age-related functional decline; decreased muscle strength and function; muscle weakness due to HIV; chronic renal failure, decreased bone density and growth; catabolic side effects of glucocorticoids; chronic fatigue syndrome; delayed healing of bone fractures; acute fatigue syndrome and loss of muscle mass after elective surgery; cachexia; chronic catabolic state; eating disorders; side effects of chemotherapy; exhaustion; Depression increased excitability; stress growth retardation; symptoms of senile degradation; decreased cognitive function; anemia male contraception; infertility syndrome X; diabetes complications and obesity. 10. The use according to claim 9, where said disease or disorder is selected from the group consisting of hypogonadism, in particular, but not only secondary hypogonadism and the resulting diseases or disorders and age-related testosterone deficiency and the resulting diseases or disorders, and said selective estrogen receptor modulator is a triphenylbutene compound of formula (I)

where R1 represents H, halogen, OCH ₃ or OH; and R2 is a)

where X represents O, NH or S; and n is an integer from 1 to 4; and R4 and R5, which are the same or different, are alkyl with a carbon number of 1 to 4, H, —CH ₂ C or —CH ₂ CH ₂ OH; or R4 and R5 form N a five- or six-membered ring or a heteroaromatic ring; or b) -Y- (CH ₂ ) _n CH ₂ -O-R6 where Y represents O, NH or S, and n is an integer from 1 to 4; and R6 is H, —CH ₂ CH ₂ OH or —CH ₂ CH ₂ Cl; or c) 2,3-dihydroxypropoxy, 2-methylsulfamylethoxy, 2-chloroethoxy, 1-ethyl-2-hydroxyethoxy, 2,2-diethyl-2-hydroxyethoxy or carboxymethoxy; and R3 is H, halogen, OH or —OCH ₃ or an isomer thereof, a mixture of isomers, a metabolite or a pharmaceutical salt. 11. The use of claim 10, where the specified selective modulator of estrogen receptors is a triphenylbutene compound of the formula (I)

where R1 represents H, halogen, OCH ₃ or OH; and R2 is a)

where i) X represents NH or S; and n is an integer from 1 to 4; and R4 and R5, which are the same or different, are alkyl with a carbon number of 1 to 4, H, —CH ₂ C or —CH ₂ CH ₂ OH; or R4 and R5 form N a five- or six-membered ring or a heteroaromatic ring; or where ii) X represents O, and n is an integer from 1 to 4; and one of R4 and R5 is —CH ₂ CCH or —CH ₂ CH ₂ OH, and the other is H or C ₁ -C ₄ alkyl; or R4 and R5 form an imidazole ring containing an N six-membered ring or a heteroaromatic ring; or R2 is b) -Y- (CH ₂ ) _n CH ₂ -O-R6 where Y represents O, NH or S, and n is an integer from 1 to 4; and R6 is H, —CH ₂ CH ₂ OH or —CH ₂ CH ₂ Cl; or R2 is c) 2,3-dihydroxypropoxy, 2-methylthioethoxy, 2-chloroethoxy, 1-ethyl-2-hydroxyethoxy, 2,2-diethyl-2-hydroxyethoxy or carboxymethoxy; and R3 is H, halogen, OH or —OCH ₃ or an isomer thereof, a mixture of isomers, a metabolite or a pharmaceutical salt. 12. The application of claim 11, where the selective modulator of estrogen receptors selected from the group consisting of (Z) -2- [3- (4-chloro-1,2-diphenylbut-1-enyl) phenoxy] ethanol, (Z) -2- {2- [4- (4-chloro-1,2-diphenylbut-1-enyl) phenoxy] ethoxy} ethanol (fispemifene), (Z) - {2- [3- (4-chloro-1,2-diphenylbut-1-enyl) phenoxy] ethyl} dimethylamine, (E) -3- {4-chloro-1- [4- (2-hydroxyethoxy) phenyl] -2-phenylbut-1-enyl} phenol, (E) -3- {4-chloro-1- [4- (2-imidazol-1-ylethoxy) phenyl] -2-phenylbut-1-enyl} phenol, (Z) -3- {4-chloro-1- [4- (2-imidazol-1-ylethoxy) phenyl] -2-phenylbut-1-enyl} phenol and (Z) -2- [4- (4-chloro-1,2-diphenylbut-1-enyl) phenoxy] ethanol (ospemifene) or an isomer thereof, a mixture of isomers, a metabolite or a pharmaceutically acceptable salt. 13. The use of claim 12, wherein the selective estrogen receptor modulator is fispemifene or an isomer thereof, a mixture of isomers, a metabolite, or a pharmaceutically acceptable salt thereof.