C - Chemistry – Metallurgy – 07 – D
Patent
C - Chemistry, Metallurgy
07
D
C07D 513/04 (2006.01) A61K 31/40 (2006.01) A61P 19/00 (2006.01) C07D 471/04 (2006.01) C07D 487/04 (2006.01) C07D 498/04 (2006.01)
Patent
CA 2356099
48 Treating or preventing degeneration or destruction of articular cartilage and/or subchondral bone in the affected joint of a mammal is accomplished by administering a compound of Formula (I): Image Formel 1 wherein the variables have the meanings given in the present description. A preferred compound of formula (I) is Image This treatment ameliorates, diminishes, actively treats, reverses or prevents any injury, damage or loss of articular cartilage or subchondral bone subsequent to said early stage of said degeneration. Whether or not a mammal needs such treatment is determined by whether or not it exhibits a statistically significant deviation from normal standard values in synovial fluid or membrane from the affected joint, with respect to at least five of the following substances: increased interleukin-1 beta (IL-1.beta.); increased tumor necrosis factor alpha (TNF.alpha.); increased ratio of IL-1.beta. to IL-1 receptor antagonist protein (IL-1Ra); increased expression of p55 TNF receptors (p55 TNF-R); increased interleukin-6 (IL-6); increased leukemia inhibitory factor (LIF); decreased insulin-like growth factor-1 (IGF-1); decreased transforming growth factor beta (TGF.beta.); decreased platelet-derived growth factor (PDGF); decreased basic fibroblast growth factor (b-FGF); increased keratan sulfate; increased stromelysin; increased ratio of stromelysin to tissue inhibitor of metalloproteases (TIMP); increased osteocalcin; increased alkaline phosphatase; increased cAMP responsive to hormone challenge: increased urokinase plasminogen activator (uPA); increased cartilage oligomeric matrix protein; and increased collagenase.
Martel-Pelletier Johanne
Pelletier Jean-Pierre
Ascentia Pharma Inc.
Deeth Williams Wall Llp
Merckle Gmbh
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