KETONES AND KETONES REDUCED AS THERAPEUTIC AGENTS FOR THE TREATMENT OF OSEAS DISEASES.

摘要

Use of a compound in the manufacture of a medicament for use in the treatment of: osteoporosis, rheumatoid arthritis, bone disease associated with cancer, Paget's disease, or aseptic loosening of prosthetic implants; wherein the compound is selected from the compounds of the formulas, and pharmaceutically acceptable salts, solvates, amides, esters, and ethers thereof: wherein: Ar1 is independently a biphenyl, and is not substituted or substituted with one or more groups selected from: (1) carboxylic acid; (2) ester; (3) amido; (4) acyl; (5) halo; (6) cyano; (7) nitro; (8) hydroxy; (9) ether; (10) thiol; (11) thioether; (12) acyloxy; (13) amino; (14) acylamino; (15) aminoacylamino; (16) sulfonamino; (17) sulfonyl; (18) sulfonate; (19) sulfonamido; (20) C5-20 aryl-C1-7 alkyl; (21) C5-20 aryl; (22) C3-20 heterocyclyl; (23) C1-7 alkyl; (24) oxo; (25) imino; (26) hydroxyimino; and (27) phosphate; Ralk is independently a C4-8 alkylene group, and is not substituted, or is substituted by one or more substituents selected from: halogen, hydroxy, C1-7 alkoxy, amino, and amido; -ORO, if present, is independently -OH or -ORK; -ORK, if present, is independently selected from: -O- RK1; -O-C (= O) RK2; -O-C (= O) ORK3; -O-S (= O) 2ORK4; wherein: each of RK1, RK2, RK3, and RK4 is independently C5-20 aryl-C1-7 alkyl, C5-20 aryl, C3-20 heterocyclyl, or C1-7 alkyl, and is optionally substituted; and each of RK3 and RK4 can also be -H; Q is independently -OH or -OROT; where: -OROT, if present, is independently: -O-RE1; wherein: RE1 is independently: C5-20 aryl-C1-7 alkyl, unsubstituted or substituted with one or more groups selected from: (1) carboxylic acid; (2) ester; (3) amido; (4) acyl; (5) halo; (6) cyano; (7) nitro; (8) hydroxy; (9) ether; (10) thiol; (11) thioether; (12) acyloxy; (13) amino; (14) acylamino; (15) aminoacylamino; (16) sulfonamino; (17) sulfonyl; (18) sulfonate; (19) sulfonamido; (20) C5-20 aryl-C1-7 alkyl; (21) C5-20 aryl; (22) C3-20 heterocyclyl; (23) C1-7 alkyl; (24) oxo; (25) imino; (26) hydroxyimino; and (27) phosphate; C5-20 aryl, unsubstituted or substituted with one or more groups selected from: (1) carboxylic acid; (2) ester; (3) amido; (4) acyl; (5) halo; (6) cyano; (7) nitro; (8) hydroxy; (9) ether; (10) thiol; (11) thioether; (12) acyloxy; (13) amino; (14) acylamino; (15) aminoacylamino; (16) sulfonamino; (17) sulfonyl; (18) sulfonate; (19) sulfonamido; (20) C5-20 aryl-C1-7 alkyl; (21) C5-20 aryl; (22) C3-20 heterocyclyl; (23) C1-7 alkyl; (24) oxo; (25) imino; (26) hydroxyimino; and (27) phosphate; C3-20 heterocyclyl, unsubstituted or substituted with one or more groups selected from: (1) carboxylic acid; (2) ester; (3) amido; (4) acyl; (5) halo; (6) cyano; (7) nitro; (8) hydroxy; (9) ether; (10) thiol; (11) thioether; (12) acyloxy; (13) amino; (14) acylamino; (15) aminoacylamino; (16) sulfonamino; (17) sulfonyl; (18) sulfonate; (19) sulfonamido; (20) C5-20 aryl-C1-7 alkyl; (21) C5-20 aryl; (22) C3-20 heterocyclyl; (23) C1-7 alkyl; (24) oxo; (25) imino; (26) hydroxyimino; and (27) phosphate; C1-7 alkyl, unsubstituted or substituted with one or more groups selected from: (1) carboxylic acid; (2) ester; (3) amido; (4) acyl; (5) halo; (6) cyano; (7) nitro; (8) hydroxy; (9) ether; (10) thiol; (11) thioether; (12) acyloxy; (13) amino; (14) acylamino; (15) aminoacylamino; (16) sulfonamino; (17) sulfonyl; (18) sulfonate; (19) sulfonamido; (20) C5-20 aryl-C1-7 alkyl; (21) C5-20 aryl; (22) C3-20 heterocyclyl; (23) C1-7 alkyl; (24) oxo; (25) imino; (26) hydroxyimino; and (27) phosphate; wherein the carbonyl group (-C (= O) -) in formula (1) is optionally replaced with a group selected from the following, wherein each R is independently C5-20 aryl-C1-7 alkyl, C5 aryl -20, C3-20 heterocyclyl, or C1-7 alkyl, and is optionally substituted: with the proviso that, if -OROT is -O-RE1, then RE1 is not a phenyl group substituted with a sulfonyl group; and with the proviso that -ORO, if present, is different from siloxy.