Substituted 6-aza-isoindolin-1-one derivatives

Abstract

Disclosed are compounds of Formula 1, and pharmaceutically acceptable salts thereof, wherein G, p, R 1 , R 2 , R 3a , R 4 , and R 5 are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating disorders, diseases, and conditions involving the immune system and inflammation, including rheumatoid arthritis, cancer, and other disorders, diseases, and conditions for which inhibition of SYK is indicated.

1 . A compound of Formula 1, 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         G is selected from O and CH 2 ; 
         R 1  and R 2  are each independently selected from hydrogen, halo, C 1-3  alkyl, and C 1-3  haloalkyl; or 
         R 1  and R 2 , together with the atom to which they are attached, form a C 3-6  cycloalkylidene; 
         each R 3a  is independently selected from halo, oxo, —NO 2 , —CN, R 6 , and R 7 ; 
         R 4  is selected from 
       
       
         
           
           
               
               
           
         
         
           wherein   represents a point of attachment; 
         
         R 4a  and R 4b  are each independently selected from hydrogen, halo, —CN, R 6 , and R 7 , provided that (a) if R 4a  is hydrogen, then R 4b  is not unsubstituted methyl; (b) if R 4b  is hydrogen, then R 4a  is not hydrogen or unsubstituted methyl; and (c) if R 4b  is hydrogen and G is O, then R 4a  is not chloro; or 
         R 4a  and R 4b , together with the atoms to which they are attached, form a phenylene or a C 3-5  heteroarylene, each optionally substituted with from one to four substituents independently selected from halo, oxo, —CN, R 6 , and R 7 , wherein the C 3-5  heteroarylene moiety has 5 or 6 ring atoms and 1 or 2 are heteroatoms, each of the heteroatoms being N; 
         R 4c  is selected from hydrogen, halo, —CN, R 6 , and R 7 , provided that when G is O, R 4c  is not unsubstituted methyl; 
         R 4d  and R 4e  are each independently selected from hydrogen, halo, —CN, R 6 , and R 7 ; or 
         R 4d  and R 4e , together with the atoms to which they are attached, form a C 3-5  heterocycle-diyl or a C 3-5  heteroarylene, each having 5 or 6 ring atoms, at least one heteroatom which is N, and optionally 1 or 2 additional heteroatoms independently selected from N, O, and S, and wherein the C 3-5  heterocycle-diyl or the C 3-5  heteroarylene is optionally substituted with from one to four substituents independently selected from halo, oxo, —CN, R 6 , and R 7 ; 
         R 4f  is selected from C 3-8  cycloalkyl, C 2-5  heterocyclyl, C 6-14  aryl, and C 1-9  heteroaryl, each optionally substituted with from one to five substituents independently selected from halo, oxo, —CN, R 6 , and R 7 ; 
         R 4g  and R 4h  are each independently selected from hydrogen, halo, C 1-3  alkyl, and C 1-3  haloalkyl; or 
         R 4g  and R 4h , together with the atom to which they are attached, form a C 3-6  cycloalkylidene; 
         R 5  is selected from hydrogen, halo, —CN, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 2-5  heterocyclyl, C 1-5  heteroaryl, and R 10 , wherein the alkyl, alkenyl, and alkynyl moieties are each optionally substituted with from one to five substituents independently selected from halo, —CN, oxo, and R 10 , and wherein the heterocyclyl moiety has 3 to 6 ring atoms and the heteroaryl moiety has 5 or 6 ring atoms, and the heterocyclyl and heteroaryl moieties are each optionally substituted with from one to four substituents independently selected from halo, —NO 2 , —CN, C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 1-4  haloalkyl, and R 10 ; 
         each R 6  is independently selected
 from —OR 8 , —N(R 8 )R 9 , —NR 8 C(O)R 9 , —C(O)R 8 , —C(O)OR 8 , —C(O)N(R 8 )R 9 , —C(O)N(R 8 )OR 9 , —C(O)N(R 8 )S(O) 2 R 9 , —N(R 8 )S(O) 2 R 9 , —S(O) n R 8 , and —S(O) 2 N(R 8 )R 9 ; 
 
         each R 7  is independently selected from C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl,
 C 3-6  cycloalkyl-(CH 2 ) m —, C 6-14  aryl-(CH 2 ) m —, C 2-5  heterocyclyl-(CH 2 ) m —, and 
 C 1-9  heteroaryl-(CH 2 ) m —, each optionally substituted with from one to five substituents independently selected from halo, oxo, —NO 2 , —CN, C 1-6  alkyl, C 1-6  haloalkyl, and R 10 ; 
 
         each R 8  and R 9  is independently selected from hydrogen, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3-6  cycloalkyl-(CH 2 ) m —, C 6-14  aryl-(CH 2 ) m —, C 2-5  heterocyclyl-(CH 2 ) m —, and C 1-9  heteroaryl-(CH 2 ) m —, each non-hydrogen substituent optionally substituted with from one to five substituents independently selected from halo, oxo, —NO 2 , —CN, C 1-6  alkyl, C 1-6  haloalkyl, and R 10 ; 
         each R 10  is independently selected
 from —OR 11 , —N(R 11 )R 12 , —N(R 11 )C(O)R 12 , —C(O)R 11 , —C(O)OR 11 , —C(O)N(R 11 )R 12 , —C(O) N(R 11 )OR 12 , —C(O)N(R 11 )S(O) 2 R 12 , —NR 11 S(O) 2 R 12 , —S(O) n R 11 , and —S(O) 2 N(R 11 )R 12 ; 
 
         each R 11  and R 12  is independently selected from hydrogen and C 1-6  alkyl; 
         each n is independently selected from 0, 1 and 2; 
         each m is independently selected from 0, 1, 2, 3, and 4; 
         each p is independently selected from 0, 1, 2, 3, 4, 5, and 6; 
         wherein each of the heteroaryl moieties recited for R 4f , R 7 , R 8 , and R 9  has 1 to 4 heteroatoms independently selected from N, O, and S, and each of the heterocyclyl moieties recited for R 4f , R 7 , R 8 , and R 9  has 1 or 2 heteroatoms independently selected from N, O, and S. 
       
     
     
         2 . A compound or pharmaceutically acceptable salt according to  claim 1 , wherein R 1  and R 2  are both hydrogen. 
     
     
         3 . A compound or pharmaceutically acceptable salt according to  claim 1 , wherein R 5  is selected from hydrogen, halo, and C 1-4  alkyl. 
     
     
         4 . A compound or pharmaceutically acceptable salt according to  claim 1 , wherein p is 0. 
     
     
         5 . A compound or pharmaceutically acceptable salt according to  claim 1 , wherein R 4  is selected from: 
       
         
           
           
               
               
           
         
       
     
     
         6 . A compound or pharmaceutically acceptable salt according to  claim 5 , wherein R 4  is 
       
         
           
           
               
               
           
         
       
     
     
         7 . A compound or pharmaceutically acceptable salt according to  claim 5 , wherein R 4  is 
       
         
           
           
               
               
           
         
       
     
     
         8 . A compound or pharmaceutically acceptable salt according to  claim 5 , wherein R 4  is 
       
         
           
           
               
               
           
         
       
     
     
         9 . A compound or pharmaceutically acceptable salt according to  claim 1 , wherein R 4  is selected from: 
       
         
           
           
               
               
           
         
       
     
     
         10 . A compound or pharmaceutically acceptable salt according to  claim 1 , wherein G is CH 2 . 
     
     
         11 . A compound or pharmaceutically acceptable salt according to  claim 1 , wherein G is O. 
     
     
         12 . A compound according to  claim 1 , which is selected from the following compounds:
 6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-4-(3-(difluoromethyl)isothiazol-5-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-4-(3-ethylisothiazol-5-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-4-(3-ethylisothiazol-5-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(isothiazol-5-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-4-(isothiazol-5-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-4-(3-cyclopropylisothiazol-5-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(5-fluorobenzo[b]thiophen-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   5-(6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)thiophene-2-carbonitrile;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(thieno[2,3-c]pyridin-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   5-(6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)thiophene-2-carbonitrile;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(5-fluorothiophen-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(thieno[2,3-b]pyridin-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-4-(thieno[2,3-b]pyridin-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-4-(thieno[2,3-c]pyridin-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-4-(5-fluorobenzo[b]thiophen-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(thieno[3,2-c]pyridin-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-4-(thieno[3,2-c]pyridin-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(6-fluorobenzo[b]thiophen-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-4-(6-fluorobenzo[b]thiophen-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   2-(6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)benzo[b]thiophene-5-carbonitrile;   2-(6-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)benzo[b]thiophene-5-carbonitrile;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(4-fluorobenzo[b]thiophen-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-4-(4-fluorobenzo[b]thiophen-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(thieno[3,2-b]pyridin-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-4-(thieno[3,2-b]pyridin-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(4-fluorothiophen-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-4-(4-fluorothiophen-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-4-(1-methyl-1H-thieno[3,2-c]pyrazol-5-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(1-methyl-1H-thieno[3,2-c]pyrazol-5-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-4-(1,3-dimethyl-1H-thieno[3,2-c]pyrazol-5-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-4-(1,3-dimethyl-1H-thieno[3,2-c]pyrazol-5-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-4-(2,3-dimethyl-2H-thieno[3,2-c]pyrazol-5-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-4-(2,3-dimethyl-2H-thieno[3,2-c]pyrazol-5-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-4-(3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazin-7-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-4-(1,3-dimethyl-1H-thieno[2,3-c]pyrazol-5-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-4-(1,3-dimethyl-1H-thieno[2,3-c]pyrazol-5-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   Ethyl 2-(6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)indolizine-7-carboxylate;   2-(6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)indolizine-7-carboxylic acid;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(1-oxo-2,3-dihydro-1H-pyrrolizin-6-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-4-(3-methylisothiazol-5-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-4-(phenylethynyl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(phenylethynyl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-4-(4-fluorostyryl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(4-fluorostyryl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-4-phenethyl-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-7-fluoro-4-phenethyl-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-4-(4-chlorophenethyl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((1R,2S)-2-Aminocyclohexylamino)-4-(4-chlorostyryl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-4-(4-chlorostyryl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   (R)-6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-4-(5-fluoropyrazolo[1,5-a]pyridin-3-yl)-1-methyl-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   (S)-6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-4-(5-fluoropyrazolo[1,5-a]pyridin-3-yl)-1-methyl-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   (R)-6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-1-methyl-4-(5-methylpyrazolo[1, 5-a]pyridin-3-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   (S)-6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-1-methyl-4-(5-methylpyrazolo[1,5-a]pyridin-3-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   (R)-6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-7-fluoro-1-methyl-4-(3-methylisothiazol-5-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   (S)-6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-7-fluoro-1-methyl-4-(3-methylisothiazol-5-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-7-fluoro-4-(5-methylpyrazolo[1,5-a]pyridin-3-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-4-(5-methylpyrazolo[1,5-a]pyridin-3-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   a stereoisomer of any of the aforementioned compounds; and   a pharmaceutically acceptable salt of any of the aforementioned compounds or stereoisomers.   
     
     
         13 . A compound according to  claim 1 , which is selected from the following compounds:
 6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-7-fluoro-4-(indolizin-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   2-(6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)indolizine-7-carbonitrile;   6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-7-fluoro-4-(7-fluoroindolizin-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-7-fluoro-4-(1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-7-fluoro-4-(1-methyl-1H-pyrrolo[1,2-b]pyrazol-5-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-7-fluoro-4-(3-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-7-fluoro-4-(1-methyl-1H-pyrrolo[1,2-a]imidazol-6-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-7-fluoro-4-(pyrrolo[2,1-b]oxazol-6-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-4-(indolizin-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   2-(6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)indolizine-7-carbonitrile;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-4-(7-fluoroindolizin-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-4-(1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-4-(1-methyl-1H-pyrrolo[12-b]pyrazol-5-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-4-(3-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-4-(1-methyl-1H-pyrrolo[1,2-a]imidazol-6-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-4-(pyrrolo[2,1-b]oxazol-6-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-4-(8-oxo-5,6,7,8-tetrahydroindolizin-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-7-fluoro-4-(8-oxo-5,6,7,8-tetrahydroindolizin-2-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-7-fluoro-4-(3-methyl-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazin-7-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-4-(3,3-dimethyl-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazin-7-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-4-(3-ethyl-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazin-7-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-7-fluoro-4-(3-isopropyl-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazin-7-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-7-fluoro-4-(1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-7-fluoro-4-(2-methyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((3R,4R)-3-Aminotetrahydro-2H-pyran-4-yl)amino)-4-(2-ethyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-4-(3-methyl-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazin-7-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-4-(3,3-dimethyl-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazin-7-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-4-(3-ethyl-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazin-7-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-4-(3-isopropyl-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazin-7-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-4-(1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-7-fluoro-4-(2-methyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   6-(((1R,2S)-2-Aminocyclohexyl)amino)-4-(2-ethyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one;   a stereoisomer of any of the aforementioned compounds; and   a pharmaceutically acceptable salt of any of the aforementioned compounds or stereoisomers.   
     
     
         14 . A compound which is 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one, a stereoisomer thereof, or a pharmaceutically acceptable salt of the compound or stereoisomer. 
     
     
         15 . A pharmaceutical composition comprising:
 a compound or pharmaceutically acceptable salt as defined in  claim 1 ; and   a pharmaceutically acceptable excipient.   
     
     
         16 - 17 . (canceled) 
     
     
         18 . A method of treating a disease or condition in a subject for which a SYK inhibitor is indicated, the method comprising administering to the subject an effective amount of a compound or pharmaceutically acceptable salt as defined in  claim 1 . 
     
     
         19 . A method of treating a disease or condition in a subject, the method comprising administering to the subject an effective amount of a compound or pharmaceutically acceptable salt as defined in  claim 1 , wherein the disease or condition is selected from allergic rhinitis, allergic asthma, atopic dermatitis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, psoriasis, immune thrombocytopenic purpura, inflammatory bowel disease, Behcet's disease, graft versus host disease, chronic obstructive pulmonary disease, and thrombosis. 
     
     
         20 . A method of treating a disease or condition in a subject, the method comprising administering to the subject an effective amount of a compound or pharmaceutically acceptable salt as defined in  claim 1 , wherein the disease or condition is selected from cancer. 
     
     
         21 . A method according to  claim 20 , wherein the disease or condition is selected from acute myeloid leukemia, B-cell chronic lymphocytic leukemia, B-cell lymphoma, and T-cell lymphoma. 
     
     
         22 . A method according to  claim 20 , wherein the disease or condition is selected from brain cancer, lung cancer, squamous cell cancer, bladder cancer, gastric cancer, pancreatic cancer, breast cancer, cancer of the head, neck cancer, renal cancer, kidney cancer, ovarian cancer, prostate cancer, colorectal cancer, prostate cancer, colon cancer, epidermoid cancer, esophageal cancer, testicular cancer, gynecological cancer, and thyroid cancer. 
     
     
         23 . A combination of an effective amount of a compound or pharmaceutically acceptable salt as defined in  claim 1 , and at least one additional pharmacologically active agent. 
     
     
         24 . A combination according to  claim 23 , wherein the additional pharmacologically active agent is a DMARD. 
     
     
         25 . A combination according to  claim 24 , wherein the DMARD is methotrexate.