The University Court of the University of Aberdeen

Pimco 2664 Limited

Probi Ab

Stuart Hamilton Ralston

Iain Robert Greig

Robert Jurgen Van 't Hof

Aymen I I Mohamed

Robert Jurgen Van't Hof

Aymen Ibrahim Idris Mohamed

Robert J Van't Hof

Kenneth J Armour

Antonia Sophocleous

Robert Jurgen VAN'T Hof

The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl sulfonamides and related compounds (collectively referred to herein as 'BPSAAA compounds'), as described herein, and including, for example, biphenyl-4-sulfonic acid (hydroxyalkyl-phenyl)-amides and related compounds. 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, chronic obstructive pulmonary disease (COPD), atherosclerosis, 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.

Biphenyl-4-yl-sulfonic acid arylamides and their use as therapeutic agents

The present invention pertains to compounds of the following formula (wherein R, r, q, R, R, and Q are as defined herein) and compositions comprising those compounds. The compounds may be used to inhibit osteoclast survival, formation, and/or activity; 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; and/or in the treatment of conditions associated with inflammation or activation of the immune system. 

Aryl alkyl sulfonamides as therapeutic agents for the treatment of bone conditions

The present invention pertains to certain alkane diol derivatives (including, e.g., mono- and di-esters) of the formula R&#x2014;O-A-O&#x2014;R, wherein: A is a Calkylene group; Ris independently a first hydroxy protecting group (e.g., an ester group); and, Ris independently &#x2014;H or a second hydroxy protecting group (e.g., an ester group); and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrug thereof, which, inter alia, inhibit osteoclast survival, formation, and/or activity; and/or inhibit bone resorption. 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, such as osteoporosis, rheumatoid arthritis, cancer associated bone disease, Paget's disease, and the like; and/or conditions associated with inflammation or activation of the immune system.

Alkane diol derivatives as therapeutic agents for the treatment of bone conditions

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 and pharmaceutically acceptable salts, amides, esters, and ethers thereof, wherein: Ar1, R, &#x2014;ORO, and -Q are as defined herein:  The present invention also pertains to pharmaceutical compositions comprising such compounds. The compounds inhibit osteoclast survival, formation, and/or activity, and inhibit conditions mediated by osteoclasts and/or characterised by bone resorption, and are useful 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.

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

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; &#x2014;OR, if present, is independently &#x2014;OH or &#x2014;OR; &#x2014;OR, if present, is independently selected from: &#x2014;O&#x2014;R; &#x2014;O&#x2014;C(&#x2550;O)R; &#x2014;O&#x2014;C(&#x2550;O)OR; &#x2014;O&#x2014;S(&#x2550;O)2OR; Q is independently &#x2014;OH or &#x2014;OR; wherein: &#x2014;OR, if present, is independently selected from: &#x2014;O&#x2014;R; &#x2014;O&#x2014;C(&#x2550;O)&#x2014;R; &#x2014;O&#x2014;C(&#x2550;O)&#x2014;O&#x2014;R; &#x2014;O&#x2014;C(&#x2550;O)&#x2014;O&#x2014;SOR; &#x2014;O&#x2014;C(&#x2550;O)&#x2014;O&#x2014;(CH)&#x2014;COOR; &#x2014;O&#x2014;C(&#x2550;O)&#x2014;(CH)&#x2014;NRR; &#x2014;O&#x2014;C(&#x2550;O)&#x2014;(CH)&#x2014;NH&#x2014;C(&#x2550;O)R; &#x2014;O&#x2014;C(&#x2550;O)&#x2014;(CH)&#x2014;C(&#x2550;O)&#x2014;NRR; &#x2014;O&#x2014;P(&#x2550;O)(OR)(OR); &#x2014;O&#x2014;R; R, if present, is an organic group which incorporates a phosphonic acid group; with the proviso that if &#x2014;ORis &#x2014;O&#x2014;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. 

The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain 2',4&#x2032;-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 &#x2014;C(&#x2550;O)&#x2014;, &#x2014;CH(OH)&#x2014;, or &#x2014;C(&#x2550;NOR)&#x2014;; Ris independently &#x2014;H or Calkyl; J is independently: &#x2014;H, &#x2014;R, &#x2014;C(&#x2550;O)&#x2014;R, &#x2014;C(&#x2550;O)&#x2014;O&#x2014;R, &#x2014;C(&#x2550;O)&#x2014;O&#x2014;S(&#x2550;O)OR, &#x2014;C(&#x2550;O)&#x2014;(CH)&#x2014;C(&#x2550;O)OR, &#x2014;C(&#x2550;O)&#x2014;(CH)&#x2014;NRR, &#x2014;C(&#x2550;O)&#x2014;(CH)&#x2014;NR&#x2014;C(&#x2550;O)R, &#x2014;C(&#x2550;O)&#x2014;(CH)&#x2014;C(&#x2550;O)&#x2014;NRR, or &#x2014;P(&#x2550;O)(OR)(OR); wherein each of R, R, R, R, R, R, and Ris independently: &#x2014;H, Calkyl, -Ph, or &#x2014;CH-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.

Growing community of inventors

Edinburgh, United Kingdom

Stuart Hamilton Ralston