Triazolopyridine kinase inhibitors useful for the treatment of degenerative and inflammatory diseases

Abstract

A novel [1,2,4]triazolo[1,5-a]pyridine compound is disclosed that has a formula represented by the following: This compound may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, diseases involving cartilage degradation, bone and/or joint degradation, for example osteoarthritis; and/or conditions involving inflammation or immune responses, such as Crohn's disease, rheumatoid arthritis, psoriasis, allergic airways disease (e.g. asthma, rhinitis), juvenile idiopathic arthritis, colitis, inflammatory bowel diseases, endotoxin-driven disease states (e.g. complications after bypass surgery or chronic endotoxin states contributing to e.g. chronic cardiac failure), diseases involving impairment of cartilage turnover (e.g. diseases involving the anabolic stimulation of chondrocytes), congenital cartilage malformations, diseases associated with hypersecretion of IL6 and transplantation rejection (e.g. organ transplant rejection) and proliferative diseases.

1 . A compound according to Formula VIa: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound according to  claim 1 . 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the carrier is a parenteral carrier. 
     
     
         4 . The pharmaceutical composition of  claim 2 , wherein the carrier is an oral carrier. 
     
     
         5 . The pharmaceutical composition of  claim 2 , wherein the carrier is a topical carrier. 
     
     
         6 . A method of treatment, prevention or prophylaxis of diseases involving cartilage degradation, bone and/or joint degradation, for example osteoarthritis; and/or conditions involving inflammation or immune responses, such as Crohn's disease, rheumatoid arthritis, psoriasis, allergic airways disease (e.g. asthma, rhinitis), juvenile idiopathic arthritis, colitis, inflammatory bowel diseases, endotoxin-driven disease states (e.g. complications after bypass surgery or chronic endotoxin states contributing to e.g. chronic cardiac failure), diseases involving impairment of cartilage turnover (e.g. diseases involving the anabolic stimulation of chondrocytes), congenital cartilage malformations, diseases associated with hypersecretion of IL6 and transplantation rejection (e.g. organ transplant rejection), comprising administering to a subject a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         7 . A method of treatment, prevention or prophylaxis of proliferative diseases, comprising administering to a subject a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         8 . The method according to  claim 6 , wherein the condition is selected from diseases involving a method of the anabolic stimulation of chondrocytes. 
     
     
         9 . The method according to  claim 6 , wherein the condition is selected from psoriatic arthritis, juvenile rheumatoid arthritis, gouty arthritis, septic or infectious arthritis, reactive arthritis, reflex sympathetic dystrophy, algodystrophy, Tietze syndrome or costal chondritis, fibromyalgia, osteochondritis, neurogenic or neuropathic arthritis, arthropathy, endemic forms of arthritis like osteoarthritis deformans endemica, Mseleni disease and Handigodu disease; degeneration resulting from fibromyalgia, systemic lupus erythematosus, scleroderma and ankylosing spondylitis. 
     
     
         10 . A method of treatment or prophylaxis of a disease involving degradation of cartilage, comprising administering to a subject a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         11 . A method of treatment or prevention of osteoarthritis, comprising administering to a subject, a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         12 . A method of treatment or prevention of a condition or a disease involving inflammation, comprising administering to a subject a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         13 . A method of treatment, prevention or prophylaxis of diseases involving cartilage degradation, bone and/or joint degradation, for example osteoarthritis; and/or conditions involving inflammation or immune responses, such as Crohn's disease, rheumatoid arthritis, psoriasis, allergic airways disease (e.g. asthma, rhinitis), juvenile idiopathic arthritis, colitis, inflammatory bowel diseases, endotoxin-driven disease states (e.g. complications after bypass surgery or chronic endotoxin states contributing to e.g. chronic cardiac failure), diseases involving impairment of cartilage turnover (e.g. diseases involving the anabolic stimulation of chondrocytes), congenital cartilage malformations, diseases associated with hypersecretion of IL6 and transplantation rejection (e.g. organ transplant rejection), comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition according to  claim 2 . 
     
     
         14 . The method according to  claim 13 , wherein the condition is selected from diseases involving a method of the anabolic stimulation of chondrocytes. 
     
     
         15 . The method according to  claim 13 , wherein the condition is selected from psoriatic arthritis, juvenile rheumatoid arthritis, gouty arthritis, septic or infectious arthritis, reactive arthritis, reflex sympathetic dystrophy, algodystrophy, Tietze syndrome or costal chondritis, fibromyalgia, osteochondritis, neurogenic or neuropathic arthritis, arthropathy, endemic forms of arthritis like osteoarthritis deformans endemica, Mseleni disease and Handigodu disease; degeneration resulting from fibromyalgia, systemic lupus erythematosus, scleroderma and ankylosing spondylitis. 
     
     
         16 . A method of treatment, prevention or prophylaxis of proliferative diseases, comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition according to  claim 2 . 
     
     
         17 . A method of treatment or prophylaxis of a disease involving degradation of cartilage, comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition according to  claim 2 . 
     
     
         18 . A method of treatment or prevention of osteoarthritis, comprising administering to a subject, a therapeutically effective amount of a pharmaceutical composition according to  claim 2 . 
     
     
         19 . A method of treatment or prevention of a condition or a disease involving inflammation, comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition according to  claim 2 .