Patent EA-003471-B1 (EA)
Title: 2-ARYLBENZO[b]THIOPHENES USEFUL FOR THE TREATMENT OF ESTROGEN DEPRIVATION SYNDROME
Inventor: CULLINAN GEORGE JOSEPH
IPC: A61P19/10
Filed: 1998-11-09
Abstract: 1. A method for inhibiting estrogen deprivation syndrome in mammals which includes administering to a mammal in need thereof an effective amount of a compound of formula I: where: R and R<1> are independently hydrogen, hydroxy, or a solvate thereof. 2. A method according to Claim 1 where the mammal is a female human. 3. A method according to Claim 2 where the pathology of estrogen deprivation syndrome is osteoporosis. 4. A method according to Claim 2 where the pathology of estrogen deprivation syndrome is hyperlipidemia. 5. A use according to Claim 2 where the female human is peri- or post-menopausal. 6. A method for inhibiting estrogen deprivation syndrome in mammals which comprises administering to a mammal in need thereof an effective amount of a compound of formula I: where: R and R<1> are independently hydroxy, or solvate thereof or a compound of formula II where: R<2> and R<3> are independently hydrogen, C1-C6 alkyl, CO (C1-C6 alkyl), or OCOAr; R<4> is pyrolidin-1-yl, piperidin-1-yl, or hexamethyleneimin-1-yl; where the nitrogen of the R<4> group is optionally the N-oxide; or a pharmaceutical salt or solvate thereof. 7. A method according to Claim 6 where the mammal is a female human. 8. A method according to Claim 7 where the pathology of said estrogen deprivation syndrome is osteoporosis. 9. A method according to Claim 8 where the pathology of said estrogen deprivation syndrome is hyperlipidemia. 10. A method according to Claim 6 where the compound of formula II is the hydrochloride salt, R<2> and R<3> are both hydrogen, and R<4> is piperidin-1-yl. 11. A method according to Claim 7 where the female human is menopausal. 12. A method according to Claim 6 where said compound of formula I is 2-(4-hydroxyphenyl)-6-hydroxybenzo(b]thiophene, and said compound of formula II is raloxifene hydrochloride and pathology is osteoporosis. 13. A pharmaceutical formulation comprising a compound of formula I: where: R and R<1> are independently hydroxy, or a solvate thereof, or a compound of formula II R<2> and R<3> are independently hydrogen, C1-C6 alkyl, CO(C1-C6 alkyl), or CQAr; R<4> is pyrolidin-1-yl, piperidin-1-yl, or hexamethyleneimin-1-yl; where the nitrogen of the R<4> group is optionally the N-oxide; or a pharmaceutical salt or solvate thereof; and pharmaceutical carriers, excipients, or diluents. 14. A formulation according to Claim 13 comprising 0.001 to 60 mg of a compound of formula I or a solvate thereof, and 1 to 120 mg of a compound of formula II being raloxifene hydrochloride. 15. A formulation according to Claim 14 comprising 0.001 to 1 mg of the compound of formula I, or a solvate thereof, and 59 to 59.999 mg of raloxifene hydrochloride. 16. A formulation according to Claim 15 comprising 0.001 to 0.1 mg of the compound of formula I, or a solvate thereof, and 59.1 to 59.999 mg of raloxifene hydrochloride. 17. An article of manufacture comprising packaging material and a pharmaceutical formulation contained within the packaging material, where the packaging material comprises a label which indicates the pharmaceutical formulation may be administered for inhibiting a pathology of estrogen deprivation syndrome, and where the pharmaceutical formulation comprises a compound of formula I: where: R and R<1> are independently hydroxy or a solvate thereof; and a compound of the formula: or a solvate thereof. 18. An article of manufacture according to Claim 17 which comprises 0.001 to 1 mg of a compound of formula I or a solvate thereof, and 59 to 59.999 mg of a compound of the formula: or a solvate thereof. 19. An article of manufacture according to Claim 17 wherein said pathology is osteoporosis.