Ketones and reduced ketones as therapeutic agents for the treatment of bone conditions

Abstract

The present invention pertains to certain ketones and reduced ketones and derivatives thereof which, inter alia, inhibit osteoclast survival, formation, and/or activity; and/or inhibit bone resorption, and more particularly to compounds of the formulae: (1) (2) wherein: Aris independently a biphenyl, phenanthryl, fluorenyl, or carbazolyl, and is optionally substituted; Ris independently a Calkylene group, and is optionally substituted; —OR, if present, is independently —OH or —OR; —OR, if present, is independently selected from: —O—R; —O—C(═O)R; —O—C(═O)OR; —O—S(═O)2OR; Q is independently —OH or —OR; wherein: —OR, if present, is independently selected from: —O—R; —O—C(═O)—R; —O—C(═O)—O—R; —O—C(═O)—O—SOR; —O—C(═O)—O—(CH)—COOR; —O—C(═O)—(CH)—NRR; —O—C(═O)—(CH)—NH—C(═O)R; —O—C(═O)—(CH)—C(═O)—NRR; —O—P(═O)(OR)(OR); —O—R; R, if present, is an organic group which incorporates a phosphonic acid group; with the proviso that if —ORis —O—R, then Ris not a phenyl group substituted with a sulfonyl group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, or prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit osteoclast survival, formation, and/or activity, and to inhibit conditions mediated by osteoclasts and/or characterised by bone resorption, in the treatment of bone disorders such as osteoporosis, rheumatoid arthritis, cancer associated bone disease, Paget's disease, aseptic loosening of prosthetic implants, and the like; and/or in the treatment of conditions associated with inflammation or activation of the immune system.