N-(4-hydroxy-4-methyl-cyclohexyl)-4-phenyl-benzenesulfonamide and n-(4-hydroxy-4-methyl-cyclohexyl)-4-(2-pyridyl)-benzenesulfonamide compounds and their therapeutic use

Abstract

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain substituted N-(4-hydroxy-4-methyl-cyclohexyl)-4-phenyl-benzenesulfonamide and N-(4-hydroxy-4-methyl-cyclohexyl)-4-(2-pyridyl)benzenesulfonamide compounds (collectively referred to herein as HMC compounds) that are useful, for example, in the treatment of disorders (e.g., diseases) including, inflammation and/or joint destruction and/or bone loss; disorders mediated by excessive and/or inappropriate and/or prolonged activation of the immune system; inflammatory and autoimmune disorders, for example, rheumatoid arthritis; psoriasis; psoriatic arthritis; chronic obstructive pulmonary disease (COPD); asthma; atherosclerosis; inflammatory bowel disease; ankylosing spondylitis; multiple sclerosis; systemic lupus erythematosus; Sjogren's syndrome; a disorder associated with bone loss, such as bone loss associated with excessive osteoclast activity in rheumatoid arthritis, osteoporosis, cancer-associated bone disease, or Paget's disease; cancer, such as a haematological malignancy, such as multiple myeloma, leukemia, or lymphoma, or a solid tumour cancer, such as bladder cancer, breast cancer (female and/or male), colon cancer, renal cell carcinoma, kidney cancer, lung cancer, pancreatic cancer, gastric cancer, prostate cancer, brain cancer, skin cancer, thyroid cancer, basal cell ameloblastoma, or melanoma; a disorder associated with fibrosis, such as systemic sclerosis or scleroderma; or a rare vasculitide, such as Behçet's disease. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, for example, in therapy.

1 . A compound selected from compounds of the following formulae, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         2 . A compound according to  claim 1 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         3 . A compound according to  claim 1 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         4 . A compound according to  claim 1 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         5 . A compound according to  claim 1 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         6 . A compound according to  claim 1 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         7 . A compound according to  claim 1 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         8 . A compound according to  claim 1 , which is a compound selected from compounds of the following formulae, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         9 . A compound according to  claim 8 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         10 . A compound according to  claim 8 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         11 . A compound according to  claim 8 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         12 . A compound according to  claim 8 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         13 . A compound according to  claim 8 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         14 . A compound according to  claim 8 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         15 . A compound according to  claim 1 , which is a compound selected from compounds of the following formulae, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         16 . A compound according to  claim 15 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         17 . A compound according to  claim 15 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         18 . A compound according to  claim 15 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         19 . A compound according to  claim 15 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         20 . A compound according to  claim 15 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         21 . A compound according to  claim 15 , which is a compound of the following formula, or a pharmaceutically acceptable salt, hydrate, or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         22 . A composition comprising a compound according to any one of  claims 1  to  21 , and a pharmaceutically acceptable carrier or diluent. 
     
     
         23 . A method of preparing a composition comprising the step of mixing a compound according to any one of  claims 1  to  21  and a pharmaceutically acceptable carrier or diluent. 
     
     
         24 . A compound according to any one of  claims 1  to  21  for use in a method of treatment of the human or animal body by therapy. 
     
     
         25 . A compound according to any one of  claims 1  to  21  for use in a method of treatment of a disorder. 
     
     
         26 . Use of a compound according to any one of  claims 1  to  21  in the manufacture of a medicament for treatment of a disorder. 
     
     
         27 . A method of treatment of a disorder comprising administering to a patient in need of treatment a therapeutically effective amount of a compound according to any one of  claims 1  to  21 . 
     
     
         28 . A compound for use according to  claim 25 , use according to  claim 26 , or a method according to  claim 27 , wherein the treatment is treatment of:
 rheumatoid arthritis; psoriasis; psoriatic arthritis; chronic obstructive pulmonary disease (COPD); asthma; atherosclerosis; inflammatory bowel disease; ankylosing spondylitis;   multiple sclerosis; systemic lupus erythematosus; Sjogren's syndrome;   a disorder associated with bone loss, such as bone loss associated with excessive osteoclast activity in rheumatoid arthritis, osteoporosis, cancer-associated bone disease, or Paget's disease;   cancer, such as a haematological malignancy, such as multiple myeloma, leukemia, or lymphoma, or a solid tumour cancer, such as bladder cancer, breast cancer (female and/or male), colon cancer, renal cell carcinoma, kidney cancer, lung cancer, pancreatic cancer, gastric cancer, prostate cancer, brain cancer, skin cancer, thyroid cancer, basal cell ameloblastoma, or melanoma;   a disorder associated with fibrosis, such as systemic sclerosis or scleroderma; or   a rare vasculitide, such as Behçet's disease.   
     
     
         29 . A compound for use according to  claim 25 , use according to  claim 26 , or a method according to  claim 27 , wherein the treatment is treatment of:
 rheumatoid arthritis; psoriasis; psoriatic arthritis; chronic obstructive pulmonary disease (COPD); asthma; atherosclerosis; inflammatory bowel disease; or ankylosing spondylitis.   
     
     
         30 . A compound for use according to  claim 25 , use according to  claim 26 , or a method according to  claim 27 , wherein the treatment is treatment of:
 multiple sclerosis; systemic lupus erythematosus; or Sjogren's syndrome.   
     
     
         31 . A compound for use according to  claim 25 , use according to  claim 26 , or a method according to  claim 27 , wherein the treatment is treatment of:
 a disorder associated with bone loss, such as bone loss associated with excessive osteoclast activity in rheumatoid arthritis, osteoporosis, cancer-associated bone disease, or Paget's disease.   
     
     
         32 . A compound for use according to  claim 25 , use according to  claim 26 , or a method according to  claim 27 , wherein the treatment is treatment of:
 cancer, such as a haematological malignancy, such as multiple myeloma, leukemia, or lymphoma, or a solid tumour cancer, such as bladder cancer, breast cancer (female and/or male), colon cancer, renal cell carcinoma, kidney cancer, lung cancer, pancreatic cancer, gastric cancer, prostate cancer, brain cancer, skin cancer, thyroid cancer, basal cell ameloblastoma, or melanoma.   
     
     
         33 . A compound for use according to  claim 25 , use according to  claim 26 , or a method according to  claim 27 , wherein the treatment is treatment of:
 a disorder associated with fibrosis, such as systemic sclerosis or scleroderma.   
     
     
         34 . A compound for use according to  claim 25 , use according to  claim 26 , or a method according to  claim 27 , wherein the treatment is treatment of:
 a rare vasculitide, such as Behçet's disease.