Novel Compounds

Abstract

The invention provides a combination comprising compounds of formula (I) or salts thereof, and one or more therapeutic agents.

1 - 12 . (canceled) 
     
     
         13 . A combination comprising:
 (i) a compound of formula (I):   
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is 9- or 10-membered bicyclic heteroaryl wherein the 9- or 10-membered bicyclic heteroaryl contains from one to three heteroatoms independently selected from oxygen and nitrogen and is optionally substituted by C 1-6 alkyl, C 3-6 cycloalkyl, halo, —CN or —NHSO 2 R 5 , or 
 pyridinyl optionally substituted by one or two substituents independently selected from C 1-6 alkyl, —OR 6 , halo and —NHSO 2 R 7 ; 
 R 2  and R 3 , together with the nitrogen atom to which they are attached, are linked to form a 6- or 7-membered heterocyclyl wherein the 6- or 7-membered heterocyclyl optionally contains an oxygen atom or a further nitrogen atom and is optionally substituted by one or two substituents independently selected from C 1-6 alkyl; 
 R 4  is hydrogen or methyl; 
 R 6  is hydrogen or C 1-4 alkyl; and 
 R 5  and R 7  are each independently C 1-6 alkyl, or phenyl optionally substituted by one or two substituents independently selected from halo; 
 or a salt thereof 
 and (2) one or more other therapeutic agents. 
 
     
     
         14 . A combination according to  claim 13 , where the compound of formula (I) is N-[5-[4-(5-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         15 . A combination according to  claim 13 , wherein the compound of formula (I) is 6-(1H-Indol-4-yl)-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3-oxazol-2-yl)-1H-indazole 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         16 . A combination according to  claim 13 , wherein the one or more therapeutic agents is selected from the group consisting of a corticosteroid, an NSAID, an anticholinergic agent, a β 2 -adrenoreceptor agonist, an antiinfective agent, and an antihistamine. 
     
     
         17 . A combination according to  claim 13 , wherein the one or more therapeutic agents is a corticosteroid or an NSAID. 
     
     
         18 . A combination according to  claim 13 , wherein the one or more therapeutic agents is an antibiotic or an antiviral. 
     
     
         19 . A pharmaceutical composition comprising a combination as defined in  claim 13  or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients. 
     
     
         20 . A method of treating a disorder mediated by inappropriate PI3-kinase activity comprising administering a safe and effective amount of a combination as defined in  claim 13 , or a pharmaceutically acceptable salt thereof, to a patient having said disorder. 
     
     
         21 . A method according to  claim 20  wherein the disorder mediated by inappropriate PI3-kinase activity is a respiratory disease, a viral infection, a non-viral respiratory infection, an allergic disease, an autoimmune disease, an inflammatory disorder, a cardiovascular disease, a hematologic malignancy, a neurodegenerative disease, pancreatitis, multiorgan failure, kidney disease, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection, lung injury, or pain. 
     
     
         22 . A method according to  claim 20  wherein the disorder mediated by inappropriate PI3-kinase activity is asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), viral respiratory tract infections, viral exacerbation of respiratory diseases, aspergillosis, leishmaniasis, allergic rhinitis, atopic dermatitis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, thrombosis, atherosclerosis, hematologic malignancy, neurodegenerative disease, pancreatitis, multiorgan failure, kidney disease, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection, lung injury, pain associated with rheumatoid arthritis or osteoarthritis, back pain, general inflammatory pain, post hepatic neuralgia, diabetic neuropathy, inflammatory neuropathic pain (trauma), trigeminal neuralgia or Central pain. 
     
     
         23 . A method according to  claim 20  wherein the disorder mediated by inappropriate PI3-kinase activity is asthma. 
     
     
         24 . A method according to  claim 20  wherein the disorder mediated by inappropriate PI3-kinase activity is COPD.