2',4'-DICHLORO-BIPHENYL-4-YL-HYDROXY-KETONES AND RELATED COMPOUNDS AND THEIR USE AS THERAPEUTIC AGENTS

摘要

The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain 2',4'-dichloro-biphenyl-4-yl-hydroxy-ketones and related compounds (collectively referred to herein as "DCBP compounds"), and more particularly to compounds selected from compounds of the following formula and pharmaceutically acceptable salts, solvates, and hydrates thereof: wherein: n is independently 1, 2, 3, or 4; W is independently -C(-O)-, -CH(OH)-, or -C(-NOR^OX)-; R^OX is independently -H or C_1-3alkyl; J is independently: -H, -R^E1, -C(-O)-R^E2, -C(-O)-O-R^E3, -C(-O)-O-S(-O)₂OR^E4, -C(-O)-(CH₂)_n-C(-O)OR^E5, -C(-O)-(CH₂)_n-NR^NE1R^NE2, -C(-O)-(CH₂)_n-NR^NE3-C(-O)R^E6, -C(-O)-(CH₂)_n-C(-O)-NR^NE4R^NE5, or -P(-O)(OR^E7)(OR^E8); wherein each of R^E1, R^E2, R^E3, R^E4, R^E5, R^E6, and R^E7 is independently: -H, C_1-3alkyl, -Ph, or -CH₂-Ph. 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, in treatment and/or prevention, for example, of inflammation and/or joint destruction and/or bone loss; of disorders mediated by excessive and/or inappropriate and/or prolonged activation of the immune system; of, inflammatory and autoimmune disorders, for example, rheumatoid arthritis, psoriasis, psoriatic arthritis, inflammatory bowel disease, ankylosing spondylitis, and the like; of disorders associated with bone loss, such as bone loss associated with excessive osteoclast activation in rheumatoid arthritis, osteoporosis, cancer associated bone disease, Paget's disease and the like.