Pyridazinone-amides derivatives

Abstract

The present invention relates to compounds of formula (I) wherein R1, Ra, Rb and Z have the meaning given in claim 1 , and their use in the prophylaxis and treatment of diseases.

1 - 15 : (canceled) 
     
     
         16 : A method for treating an autoimmune disease selected from the group consisting of asthma, rheumatoid arthritis, Acute disseminated encephalomyelitis (ADEM), Addison's disease, Alopecia areata, Ankylosing spondylitis, Antiphospholipid antibody syndrome (APS), Autoimmune hemolytic anemia, Autoimmune hepatitis, Autoimmune inner ear disease, Bullous pemphigoid, Behget's disease, Coeliac disease, Anti-transglutaminase, Chagas disease, Chronic obstructive pulmonary disease, Crohns Disease, Dermatomyositis, Diabetes mellitus type 1, Endometriosis, Goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome (GBS), Hashimoto's disease, Hidradenitis suppurativa, Kawasaki disease, IgA nephropathy, Idiopathic thrombocytopenic purpura, Interstitial cystitis, Lupus erythematosus, Mixed Connective Tissue Disease, Morphea, Multiple sclerosis (MS), Myasthenia gravis, Narcolepsy, Neuromyotonia, Pemphigus vulgaris, Pernicious anemia, Psoriasis, Psoriatic Arthritis, Polymyositis, Primary biliary cirrhosis, Rheumatoid arthritis, Schizophrenia, Scleroderma, Sjogren's syndrome, Stiff person syndrome, Systemic sclerosis, Temporal arteritis, Ulcerative Colitis, Vasculitis, Vitiligo, and Wegener's granulomatosis,
 said method comprising:   administering a pharmaceutical composition to a subject in need thereof;   wherein said pharmaceutical composition, comprises:
 a compound of Formula (I), and 
 a pharmaceutically acceptable solvate, tautomer, salt, hydrate, stereoisomer thereof, or mixtures thereof in all ratios; 
   wherein said compound of Formula (I) is as follows:   
       
         
           
           
               
               
           
         
         wherein Ra is H, Hal or Al, wherein Hal is F, Cl, Br, or I, and wherein Al is a branched or linear alkyl having 1 to 12 C-atoms, wherein one or more H atoms may be replaced by Hal, ORb, COORb, CN or N(Rb) 2  and wherein one or more CH 2 -groups may be replaced by O, CO, NRb or S, SO, SO 2 , 1,2-, 1,3- or 1,4-phenylen, —CH═CH— or —C═C—, 
         wherein Rb is H or alkyl, 
         wherein R1 is H, Hal or Al, and 
         wherein Z is a group: 
       
       
         
           
           
               
               
           
         
         wherein in said group:
 X is CH or N, 
 Y is CH or N, and 
 Rc is H, Hal or Al, 
 
         including a pharmaceutically acceptable solvate, pharmaceutically acceptable salt, or stereoisomer thereof. 
       
     
     
         17 : A method for treating a disease selected from the group consisting of Rheumatoid Arthritis, Psoriatic arthritis, Osteoarthritis, Systemic Lupus Erythematosus, Lupus nephritis, Ankylosing Spondylitis, Osteoporosis, Systemic sclerosis, Multiple Sclerosis, Psoriasis, Type I diabetes, Type II diabetes, Inflammatory Bowel Disease including Crohn's Disease and Ulcerative Colitis, Hyperimmunoglobulinemia D, periodic fever syndrome, Cryopyrin-associated periodic syndromes, Schnitzler's syndrome, Systemic juvenile idiopathic arthritis, Adult's onset Still's disease, Gout, Pseudogout, SAPHO syndrome, Castleman's disease, Sepsis, Stroke, Atherosclerosis, Celiac disease, DIRA (Deficiency of IL-1 Receptor Antagonist), Alzheimer's disease, Parkinson's disease, and cancer,
 said method comprising:   administering a pharmaceutical composition to a subject in need thereof;   wherein said pharmaceutical composition, comprises:
 a compound of Formula (I), and 
 a pharmaceutically acceptable solvate, tautomer, salt, hydrate, stereoisomer thereof, or mixtures thereof in all ratios; 
   wherein said compound of Formula (I) is as follows:   
       
         
           
           
               
               
           
         
         wherein Ra is H, Hal or Al, wherein Hal is F, Cl, Br, or I, and wherein Al is a branched or linear alkyl having 1 to 12 C-atoms, wherein one or more H atoms may be replaced by Hal, ORb, COORb, CN or N(Rb) 2  and wherein one or more CH 2 -groups may be replaced by O, CO, NRb or S, SO, SO 2 , 1,2-, 1,3- or 1,4-phenylen, —CH═CH— or —C═C—, wherein Rb is H or alkyl, 
         wherein R1 is H, Hal or Al, and 
         wherein Z is a group: 
       
       
         
           
           
               
               
           
         
         wherein in said group:
 X is CH or N, 
 Y is CH or N, and 
 Rc is H, Hal or Al, 
 
         including a pharmaceutically acceptable solvate, pharmaceutically acceptable salt, or stereoisomer thereof. 
       
     
     
         18 : The method of  claim 17 , wherein the disease is selected from the group consisting of rheumatoid arthritis, lupus nephritis, and systemic lupus erythematosus. 
     
     
         19 : A method for the treatment of a disease associated to interleukin receptor kinase (IRAK} overexpression, comprising:
 administering a pharmaceutical composition to a subject in need thereof;   wherein said pharmaceutical composition, comprises:
 a compound of Formula (I), and 
 a pharmaceutically acceptable solvate, tautomer, salt, hydrate, stereoisomer thereof, or mixtures thereof in all ratios; 
   wherein said compound of Formula (I) is as follows:   
       
         
           
           
               
               
           
         
         wherein Ra is H, Hal or Al, wherein Hal is F, Cl, Br, or I, and wherein Al is a branched or linear alkyl having 1 to 12 C-atoms, wherein one or more H atoms may be replaced by Hal, ORb, COORb, CN or N(Rb) 2  and wherein one or more CH 2 -groups may be replaced by O, CO, NRb or S, SO, SO 2 , 1,2-, 1,3- or 1,4-phenylen, —CH═CH— or —C═C—, 
         wherein Rb is H or alkyl, 
         wherein R1 is H, Hal or Al, and 
         wherein Z is a group: 
       
       
         
           
           
               
               
           
         
         wherein in said group:
 X is CH or N, 
 Y is CH or N, and 
 Rc is H, Hal or Al, 
 
         including a pharmaceutically acceptable solvate, pharmaceutically acceptable salt, or stereoisomer thereof. 
       
     
     
         20 : A kit, comprising:
 separate packs of:   (a) an effective amount of a pharmaceutical composition,   wherein said pharmaceutical composition, comprises:
 a compound of Formula (I), and 
 a pharmaceutically acceptable solvate, tautomer, salt, hydrate, stereoisomer thereof, or mixtures thereof in all ratios; 
   wherein said compound of Formula (I) is as follows:   
       
         
           
           
               
               
           
         
         wherein Ra is H, Hal or Al, wherein Hal is F, Cl, Br, or I, and wherein Al is a branched or linear alkyl having 1 to 12 C-atoms, wherein one or more H atoms may be replaced by Hal, ORb, COORb, CN or N(Rb) 2  and wherein one or more CH 2 -groups may be replaced by O, CO, NRb or S, SO, SO 2 , 1,2-, 1,3- or 1,4-phenylen, —CH═CH— or —C═C—, 
         wherein Rb is H or alkyl, 
         wherein R1 is H, Hal or Al, and 
         wherein Z is a group: 
       
       
         
           
           
               
               
           
         
         wherein in said group:
 X is CH or N, 
 Y is CH or N, and 
 Rc is H, Hal or Al, 
 
         including a pharmaceutically acceptable solvate, pharmaceutically acceptable salt, or stereoisomer thereof, 
         and 
         (b) an effective amount of a pharmaceutically active ingredient other than the compound of Formula (I) and a pharmaceutically acceptable solvate, salt and stereoisomer thereof. 
       
     
     
         21 : A pharmaceutical composition, comprising:
 at least one compound of Formula (I) and/or any a pharmaceutically acceptable solvate, salt, stereoisomer thereof, or mixtures thereof in all ratios;   wherein said compound of Formula (I) is as follows:   
       
         
           
           
               
               
           
         
         wherein Ra is H, Hal or Al, wherein Hal is F, Cl, Br, or I, and wherein Al is a branched or linear alkyl having 1 to 12 C-atoms, wherein one or more H atoms may be replaced by Hal, ORb, COORb, CN or N(Rb) 2  and wherein one or more CH 2 -groups may be replaced by O, CO, NRb or S, SO, SO 2 , 1,2-, 1,3- or 1,4-phenylen, —CH═CH— or —C═C—, 
         wherein Rb is H or alkyl, 
         wherein R1 is H, Hal or Al, and 
         wherein Z is a group: 
       
       
         
           
           
               
               
           
         
         wherein in said group:
 X is CH or N, 
 Y is CH or N, and 
 Rc is H, Hal or Al, 
 
         including a pharmaceutically acceptable solvate, pharmaceutically acceptable salt, or stereoisomer thereof. 
       
     
     
         22 : The pharmaceutical composition according to  claim 21 , further comprising:
 at least one other medicament used in the treatment of an inflammatory disease or immune disorder.   
     
     
         23 : The pharmaceutical composition according to  claim 22 , further comprising:
 at least one immunomodulating agent.