Pyrazolo [3,4-d] pyrimidine derivatives useful to treat respiratory disorders

Abstract

The present invention concerns a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, where R 1 -R 3 and Y are defined in the description, and its use in the treatment of disorders in which pi3 kinase is implicated.

1 . A method to treat a respiratory disorder, which comprises administering to a subject in need of such treatment a compound of formula (I) 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R 1  is C 1 -C 3 -alkyl, optionally substituted by one to seven fluoro groups; 
 R 2  is a 5-6 membered heteroaryl group, or R 2  is phenyl having the substitution pattern, 
 
       
         
           
           
               
               
           
         
       
       where the 5-6 membered heteroaryl or phenyl group is independently optionally substituted by one or more groups selected from List X;
 List X represents hydroxyl, cyano, nitro, C 1 -C 8 -alkyl, C 1 -C 8 -alkoxy, phenyl, a 5-6 membered heteroaryl group, a C 4 -C 6  carbocyclic group or a 5-6 membered heterocyclyl group, —(C 0 -C 4 -alkylene)-O—(C 1 -C 4 -alkylene)-R 9 , (C 0 -C 4 -alkylene)-O—(C 2 -C 4 -alkylene)-R 10 , (C 0 -C 4 -alkylene)-N(R 11 )—(C 1 -C 4 -alkylene)-R 12 , —(C 0 -C 4 -alkylene)-N(R 13 )—(C 2 -C 4 -alkylene)-R 14 , halogen, formyl, C 1 -C 8 -alkylcarbonyl, carboxy, C 1 -C 8 -alkoxycarbonyl, C 1 -C 8 -alkylaminooxycarbonyl, di-C 1 -C 8 -alkylaminooxycarbonyl, amino, C 1 -C 8 -alkylamino, di-C 1 -C 8 -alkylamino, C 1 -C 8 -alkylamidino, —N(H)C(═NH)C 1 -C 8 -alkyl, —N(C 1 -C 8 -alkyl)C(═NH)C 1 -C 8 -alkyl, C 1 -C 8 -alkylaminocarbonyl, di-C 1 -C 8 -alkylaminocarbonyl, C 1 -C 8 -alkylcarbonylamino, C 1 -C 8 -alkylcarbonyl(C 1 -C 8 -alkyhamino, C 1 -C 8 -thioalkyl, C 1 -C 8 -alkylsulfinyl, C 1 -C 8 -alkylsulfonyl, aminosulfonyl, C 1 -C 8 -alkylaminosulfonyl or di-C 1 -C 8 -alkylaminosulfonyl, where each of the afore-mentioned hydrocarbon groups may be optionally substituted, where chemically feasible, by one or more halogen, hydroxyl, amino, C 1 -C 4 -alkylamino, di-C 1 -C 4 -alkylamino or C 1 -C 4 -alkoxy groups and where said cyclic groups may be optionally substituted by one or more hydroxyl, cyano, nitro, C 1 -C 8 -alkyl C 1 -C 8 -alkoxy, halogen, C 1 -C 8 -alkylcarbonyl, carboxy, C 1 -C 8 -alkoxycarbonyl, amino, C 1 -C 8 -alkylamino, di-C 1 -C 8 -alkylamino, C 1 -C 8 -alkylaminocarbonyl, di-C 1 -C 8 -alkylaminocarbonyl, C 1 -C 8 -alkylcarbonylamino, C 1 -C 8 -alkylcarbonyl(C 1 -C 8 -alkyl)amino, C 1 -C 8 -alkylsulfonylamino, C 1 -C 8 -thioalkyl, C 1 -C 8 -alkylsulfinyl, C 1 -C 8 -alkylsulfonyl, aminosulfonyl, C 1 -C 8 -alkylaminosulfonyl or di-C 1 -C 8 -alkylaminosulfonyl groups; 
 R 9  and R 12  independently represent hydrogen, halogen, cyano, nitro, C 1 -C 8 -alkylcarbonyl, carboxy, C 1 -C 8 -alkoxycarbonyl, C 1 -C 8 -thioalkyl, C 1 -C 8 -alkylsulfinyl, C 1 -C 8 -alkylsulfonyl, aminosulfonyl, C 1 -C 8 -alkylaminosulfonyl, di-C 1 -C 8 -alkylaminosulfonyl, phenyl, a C-linked 5-6 membered heteroaryl group, a C 4 -C 6  carbocyclic group or a C-linked 5-6 membered heterocyclyl group, where said phenyl or cyclic groups may be optionally substituted by one or more hydroxyl, cyano, nitro, C 1 -C 8 -alkyl, C 1 -C 8 -alkoxy, halogen, C 1 -C 8 -alkylcarbonyl, carboxy, C 1 -C 8 -alkoxycarbonyl, amino, C 1 -C 8 -alkylamino, di-C 1 -C 8 -alkylamino, C 1 -C 8 -alkylaminocarbonyl, di-C 1 -C 8 -alkylaminocarbonyl, C 1 -C 8 -alkylcarbonylamino, C 1 -C 8 -alkylcarbonyl(C 1 -C 8 -alkyl)amino, C 1 -C 8 -alkylsulfonylamino, C 1 -C 8 -thioalkyl, C 1 -C 8 -alkylsulfinyl, C 1 -C 8 -alkylsulfonyl, aminosulfonyl, C 1 -C 8 -alkylaminosulfonyl or di-C 1 -C 8 -alkylaminosulfonyl groups; 
 R 10  and R 14  independently represent hydroxyl, C 1 -C 4 -alkoxy, amino, C 1 -C 8 -alkylamino, di-C 1 -C 8 -alkylamino, C 1 -C 8 -alkylaminocarbonyl, di-C 1 -C 8 -alkylaminocarbonyl, C 1 -C 8 -alkylcarbonylamino, C 1 -C 8 -alkylcarbonyl(C 1 -C 8 -alkyl)amino, C 1 -C 8 -alkylsulfonylamino, an N-linked 5-6 membered heteroaryl group or an N-linked 5-6 membered heterocyclyl where said cyclic groups may be optionally substituted by one or more hydroxyl, nitro, C 1 -C 8 -alkyl, C 1 -C 8 -alkoxy, halogen, C 1 -C 8 -alkylcarbonyl, carboxy, C 1 -C 8 -alkoxycarbonyl, amino, C 1 -C 8 -alkylamino, di-C 1 -C 8 -alkylamino, C 1 -C 8 -alkylaminocarbonyl, di-C 1 -C 8 -alkylaminocarbonyl, C 1 -C 8 -alkylcarbonylamino, C 1 -C 8 -alkylcarbonyl(C 1 -C 8 -alkyl)amino, C 1 -C 8 -alkylsulfonylamino, C 1 -C 8 -thioalkyl, C 1 -C 8 -alkylsulfinyl, C 1 -C 8 -alkylsulfonyl, aminosulfonyl, C 1 -C 8 -alkylaminosulfonyl or di-C 1 -C 8 -alkylaminosulfonyl groups; 
 R 11  and R 13  independently represent hydrogen or C 1 -C 6 -alkyl; 
 R 3  is amino; 
 Y represents hydrogen, C 1 -C 8 -alkyl, C 1 -C 8 -alkoxy where each of the afore-mentioned hydrocarbon groups may be optionally substituted, where chemically feasible, by one or more halogen, hydroxyl, amino, C 1 -C 8 -alkylamino, di-C 1 -C 8 -alkylamino or C 1 -C 8 -alkoxy groups, or Y represents the group —(C 0 -C 4 -alkylene)-N(R 15 )R 16 ; and 
 R 15  and R 16  independently represent hydrogen or C 1 -C 4 -alkyl, or R 15  is hydrogen and R 16  is C 1 -C 4 -alkyl substituted by phenyl, a 5-6 membered heteroaryl group, a C 4 -C 6  carbocyclic group or a 5-6 membered heterocyclyl group, where said rings are optionally substituted by one or more hydroxyl, nitro, C 1 -C 8 -alkyl, C 1 -C 8 -alkoxy, halogen, C 1 -C 8 -alkylcarbonyl, carboxy, C 1 -C 8 -alkoxycarbonyl, amino, C 1 -C 8 -alkylamino, di-C 1 -C 8 -alkylamino, C 1 -C 8 -alkylaminocarbonyl, di-C 1 -C 8 -alkylaminocarbonyl, C 1 -C 8 -alkylcarbonylamino, C 1 -C 8 -alkylcarbonyl(C 1 -C 8 -alkyl)amino, C 1 -C 8 -alkylsulfonylamino, C 1 -C 8 -thioalkyl, C 1 -C 8 -alkylsulfinyl, C 1 -C 8 -alkylsulfonyl, aminosulfonyl, C 1 -C 8 -alkylaminosulfonyl or di-C 1 -C 8 -alkylaminosulfonyl groups, where each of the afore-mentioned hydrocarbon groups may be optionally substituted, where chemically feasible by one or more halogen, hydroxyl, amino, C 1 -C 4 -alkylamino, di-C 1 -C 4 -alkylamino or C 1 -C 4 -alkoxy groups, or R 15  and R 16  together with the N to which they are attached form a 5-6-membered heterocyclic ring. 
 
     
     
         2 . The method of  claim 1 , wherein R 1  is methyl. 
     
     
         3 . The method of  claim 1 , wherein
 R 1  is methyl,   R 2  is phenyl substituted by one, two, three or four substituents selected from the group consisting of   (i) hydroxyl,   (ii) cyano,   (iii) nitro,   (iv) C 1 -C 8 -alkyl,   (v) C 1 -C 8 -haloalkyl,   (vi) C 1 -C 8 -alkoxy,   (vii) a 5-6 membered heterocyclyl group,   (viii) —O—(C 1 -C 4 -alkylene)-R 9 ,   (ix) —O—(C 2 -C 4 -alkylene)-R 10 ,   (x) —(C 0 -C 4 -alkylene)-N(R 13 )—(C 2 -C 4 -alkylene)-R 14 ,   (xi) halogen,   (xii) formyl,   (xiii) C 1 -C 8 -alkylcarbonyl,   (xiv) C 1 -C 8 -alkylaminocarbonyl,   (xv) di-C 1 -C 8 -alkylaminocarbonyl,   (xvi) C 1 -C 8 -alkylsulfonyl,   (xvii) C 1 -C 8 -alkylaminosulfonyl,   (xiii) C 1 -C 8 -alkyl substituted by hydroxy,   (xix) C 1 -C 8 -alkoxy substituted by one or more halogens, and   (xx) amino,   R 9  is selected from the group consisting of carboxy, cyano and phenyl optionally substituted by halogen, and   R 10  is selected from the group consisting of hydroxyl, C 1 -C 4 -alkoxy, an N-linked 5-6 membered heteroaryl group, and an N-linked 5-6 membered heterocyclyl.   
     
     
         4 . The method of  claim 1 , wherein
 R 2  is phenyl substituted by R 4 -R 8 ,   R 4  is selected from the group consisting of hydrogen, C 1 -C 8 -alkoxy, and halogen,   R 5  is selected from the group consisting of hydrogen, hydroxyl, cyano, formyl, C 1 -C 8 -haloalkyl, carboxy, C 1 -C 8 -alkoxy, halogen, C 1 -C 8 -alkylcarbonyl, C 1 -C 8 -alkylaminocarbonyl, methylaminocarbonyl, di-C 1 -C 8 -alkylaminocarbonyl, C 1 -C 8 -thioalkyl, C 1 -C 8 -alkylsulfinyl, C 1 -C 8 -alkylsulfonyl, —(C 0 -C 4 -alkylene)-N(R 13 )—(C 2 -C 4 -alkylene)-R 14 , and C 1 -C 8 -alkyl substituted by hydroxy,   R 6  is selected from the group consisting of hydrogen, hydroxyl, cyano, nitro, formyl, carboxy, C 1 -C 8 -alkyl, C 1 -C 8 -alkoxy, —O—(C 1 -C 4 -alkylene)-R 9 , —O—(C 2 -C 4 -alkylene)-R 10 , halogen, C 1 -C 8 -alkylcarbonyl, amino, C 1 -C 8 -alkylaminocarbonyl, C 1 -C 8 -alkylsulfonyl, and C 1 -C 8 -alkoxy substituted by one or more halogens,   R 7  is selected from the group consisting of hydrogen, hydroxyl, formyl, C 1 -C 8 -alkoxy, halogen, and —O—(C 1 -C 4 -alkylene)-R 9 ,   R 8  is selected from the group consisting of hydrogen, hydroxyl, C 1 -C 8 -alkoxy, —O—(C 2 -C 4 -alkylene)-R 10 , and —O—(C 1 -C 4 -alkylene)-R 9 ,   R 9  is selected from the group consisting of carboxy, cyano and phenyl optionally substituted by halogen, and   R 10  is selected from the group consisting of hydroxyl, C 1 -C 4 -alkoxy, an N-linked 5-6 membered heteroaryl group, and an N-linked 5-6 membered heterocyclyl,   R 13  is hydrogen, and   R 14  is di-C 1 -C 8 -alkylamino.   
     
     
         5 . The method of  claim 4 , wherein R2 is selected from:
 3-fluoro-4-methoxy-phenyl,   3-fluoro-4-hydroxy-phenyl,   3-fluoro-4-(methylsulfonylamino)-phenyl,   3-fluoro-4-hydroxy-5-bromo-phenyl,   3,5-bromo-4-hydroxy-phenyl,   3-fluoro-4-(hydroxyethoxy)-phenyl, and   3-fluoro-4-hydroxy-5-methoxy-phenyl;   
       or a pharmaceutically acceptable salt thereof. 
     
     
         6 . The method of  claim 1 , wherein Y is hydrogen. 
     
     
         7 . The method of  claim 6 , wherein R 2  is an optionally substituted heteroaryl selected from: 
       (i) pyridyl optionally substituted by halogen, e.g. fluoro, trifluoromethyl, methylsulfonyl or C 1 -C 8 -alkoxy, e.g. methoxy, 
       (ii) thienyl optionally substituted by C 1 -C 8 -alkylcarbonyl, e.g. acetyl, or halo, e.g. chloro, 
       (iii) isoxazolyl, e.g. 4-isoxazolyl, optionally substituted by one or two C 1 -C 8 -alkyl, e.g. 3,5-dimethyl, 
       (iv) furanyl, or 
       (v) pyrimidyl optionally substituted by piperazinyl or one or two C 1 -C 8 -alkoxy; 
       or a pharmaceutically acceptable salt thereof. 
     
     
         8 . The method of  claim 1 , wherein the compound of Formula (I) is selected from the group consisting of: 
       3-(3-Fluoro-4-methoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(4-Ethoxy-3-fluoro-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(3-Fluoro-4-isopropoxy-phenyl)-1-methyl-1H-pyrazolo[3,4 d]pyrimidin-6-ylamine; 
       3-(4-Methoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(3-Chloro-4-methoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin 6-ylamine; 
       3-(3-Bromo-4-methoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(3-Chloro-4-isopropoxy-phenyl)-1-methyl-1H-pyrazolo[3,4 d]pyrimidin-6-ylamine; 
       3-Benzo[1,3]dioxol-5-yl-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-1-methyl-1H-pyrazolo[3,4 d]pyrimidin-6-ylamine; 
       1-Methyl-3-(3,4,5-trimethoxy-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(3-Fluoro-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(3,4-Difluoro-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(3-Chloro-4-fluoro-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(3,4-Dichloro-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(3-Bromo-5-fluoro-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(5-Fluoro-2-methoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(3,5-Difluoro-2-methoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(2,3-Dimethyl-1H-indol-5-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(7-Fluoro-1H-indol-5-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-Benzofuran-6-yl-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       1-Methyl-3-(3-trifluoromethyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       1-[3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-phenyl]-ethanone; 
       3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-benzonitrile; 
       3-(3-Methanesulfonyl-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       1-[4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-phenyl]-ethanone; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-benzonitrile; 
       1-Methyl-3-pyridin-4-yl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(2-Chloro-pyridin-4-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(2-Methoxy-pyridin-4-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       1-Methyl-3-pyridin-3-yl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(6-Methoxy-pyridin-3-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(5-Fluoro-6-methoxy-pyridin-3-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       1-[5-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-thiophen-2-yl]-ethanone; 
       3-(4-Benzyloxy-3-fluoro-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-fluoro-phenol; 
       2-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-4-fluoro-phenol; 
       3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-5-fluoro-phenol; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-phenol; 
       3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-phenol; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-chloro-6-methoxy-phenol; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-bromo-6-fluoro-phenol; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2,6-dibromo-phenol; 
       3-[3-Bromo-5-fluoro-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-[3-Bromo-5-fluoro-4-(2-methoxy-ethoxy)-phenyl]-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       2-[4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-bromo-6-fluoro-phenoxy]-ethanol; 
       3-[3-Bromo-5-fluoro-4-(2-morpholin-4-yl-ethoxy)-phenyl]-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       2-[4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-fluoro-phenoxy]-ethanol; 
       3-[4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-fluoro-phenoxy]-propan-1-ol; 
       3-[3-Fluoro-4-(2-methoxy-ethoxy)-phenyl]-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       [4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-fluoro-phenoxy]-acetonitrile; 
       3-[3-Fluoro-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-1-methyl-1H-pyrazolo [3,4-d]pyrimidin-6-ylamine; 
       3-[3-Fluoro-4-(2-imidazol-1-yl-ethoxy)-phenyl]-1-methyl-1H-pyrazolo[3, 4-d]pyrimidin-6-ylamine; 
       3-[3-Fluoro-4-(2-morpholin-4-yl-ethoxy)-phenyl]-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-[3-Fluoro-4-(3-morpholin-4-yl-propoxy)-phenyl]-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-{3-Fluoro-4-[3-(4-methyl-piperazin-1-yl)-propoxy]-phenyl}-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       2-[2-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-4-fluoro-phenoxy]-ethanol; 
       3-(4-Amino-3-fluoro-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(3,5-Difluoro-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       1-Methyl-3-(2,3,4-trifluoro-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine trifluoroacetate; 
       3-(5-Chloro-thiophen-2-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine trifluoroacetate; 
       3-(5-Bromo-2-methoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine trifluoroacetate; 
       3-(2-Ethoxy-naphthalen-1-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine trifluoroacetate; 
       3-[3-Bromo-2-(2-fluoro-benzyloxy)-phenyl]-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine trifluoroacetate; 
       1-[3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-fluoro-phenyl]ethanone; 
       3-(4-Fluoro-2-propoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(3,5-Dimethyl-isoxazol-4-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       1-Methyl-3-m-tolyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-Furan-2-yl-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(5-Chloro-2-methoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(2,5-Dimethoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       1-Methyl-3-(4-methyl-3-nitro-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(4-Isobutyl-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-4-methoxy-benzaldehyde; 
       1-Methyl-3-(3,4,5-trifluoro-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       1-Methyl-3-quinolin-8-yl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-N-isopropyl-benzamide; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2,6-difluoro-benzaldehyde; 
       [3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-5-fluoro-phenoxy]-acetic acid; 
       3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-N-methyl-benzamide; 
       1-Methyl-3-(2-piperazin-1-yl-pyrimidin-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(2,4-Dimethoxy-pyrimidin-5-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-benzaldehyde; 
       3-(2-Methoxy-pyrimidin-5-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-N-isobutyl-benzamide; 
       3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-N-methyl-benzenesulfonamide; 
       3-(2-Methoxy-5-trifluoromethyl-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(2,4-Dimethoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(2,6-Dimethoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       2-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-4-trifluoromethyl-phenol; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-benzene-1,3-diol; 
       2-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-4-chloro-phenol; 
       3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-4-methoxy-benzoic acid; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2,6-dichloro-phenol; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-chloro-6-fluoro-phenol; 
       2-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-6-bromo-4-chloro-phenol; 
       3-(3,5-Difluoro-4-methoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-N-isopropyl-4-methoxy-benzamide; 
       3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-4-hydroxy-benzaldehyde; 
       3-(6-Amino-5-trifluoromethyl-pyridin-3-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2,6-difluoro-benzonitrile; 
       N-[3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-4-methoxy-phenyl]-N′,N′-dimethyl-propane-1,3-diamine; 
       [3-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-4-methoxy-phenyl]-methanol; 
       N-[5-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-3-fluoro-2-methoxy-phenyl]-acetamide; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2,6-difluoro-benzoic acid; 
       5-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-3-fluoro-2-hydroxy-benzaldehyde; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2,6-difluoro-phenol; 
       5-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-3-fluoro-2-hydroxy-benzonitrile; 
       3-(4-Fluoro-2-methoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-trifluoromethyl-phenol; 
       2-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-6-fluoro-phenol; 
       3-(5-Chloro-2,4-dimethoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-chloro-6-trifluoromethyl-phenol; 
       5-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-benzyloxy-3-fluoro-N,N-dimethyl-benzamide; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-6-chloro-benzene-1,3-diol; 
       3-(3-Chloro-2-methoxy-5-trifluoromethyl-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       4-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-bromo-6-chloro-benzene-1,3-diol; 
       5-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2,4-dimethoxy-N-methyl-benzenesulfonamide; 
       5-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-N-isopropyl-2,4-dimethoxy-benzenesulfonamide; 
       2-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-6-chloro-4-trifluoromethyl-phenol; 
       3-(2-Methoxy-4-trifluoromethoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       2-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-5-trifluoromethoxy-phenol; 
       3-(5-Chloro-2-methoxy-4-trifluoromethoxy-phenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       6-(6-Amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-bromo-4-chloro-3-trifluoromethoxy-phenol; 
       3-(5-Methanesulfonyl-pyridin-3-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; 
       3-(1H-Indol-6-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine; and 
       1-Methyl-3-(5-trifluoromethyl-pyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamine;
 and the pharmaceutically acceptable salts of any of these. 
 
     
     
         9 . The method of  claim 1 , wherein the respiratory condition is asthma. 
     
     
         10 . The method of  claim 1 , wherein the respiratory condition is COPD.