9h-pyrrolo-dipyridine derivatives

Abstract

The invention relates to 9H-pyrrolo-dipyridine derivatives of formula I, processes for preparing them, pharmaceutical compositions containing them and their use as radiopharmaceuticals in particular as imaging agents for the detection of Tau aggregates.

1 . A compound of general formula I, or a pharmaceutically acceptable acid addition salt, a racemic mixture or its corresponding enantiomer and/or optical isomers thereof, 
       
         
           
           
               
               
           
         
         wherein 
         R1 is heterocyclyl selected from the group consisting of azetidine, pyrrolidine, piperidine and piperazine, optionally substituted by R2; or 
         heteroaromatics selected from the group consisting of pyrazole, furan, isoxazole, thiazole, pyridine, pyridine-2-one, pyrimidine, pyrazine, pyridazine optionally substituted by one or two substituents selected from halogen, C1-C6 alkyls optionally substituted by halogens or hydroxy or C1-C6 alkoxy, cyano, amino optionally substituted by C1-C6 alkyl optionally substituted by halogens, nitro, NHC(O)—C1-C6 alkyl, C(O)N—C1-C6 alkyl optionally substituted by halogens or hydroxy or C1-C6 alkoxy, C1-C6 alkoxy optionally substituted by halogens or hydroxy or C1-C6 alkoxy, a heterocyclyl group optionally substituted by halogens or C1-C6 alkyls optionally substituted by halogens; or —NH—C(O)—R2; 
         R2 is heteroaromatics selected from the group consisting of pyrazole, furan, isoxazole, thiazole, pyridine, pyridine-2-one, pyrimidine, pyrazine, pyridazine optionally substituted by one or two substituents selected from halogen, C1-C6 alkyls optionally substituted by halogens or hydroxyl or C1-C6 alkoxy, cyano, amino, mono- or di-methyl-amino, nitro, NHC(O)—C1-C6 alkyl, C(O)N—C1-C6 alkyl optionally substituted by halogens or hydroxy or C1-C6 alkoxy, C1-C6 alkoxy optionally substituted by halogens or hydroxy or C1-C6 alkoxy, a heterocyclyl group; 
         X, Y, Z is independently N or CH, one and only one of them having to be a N; 
         A, D, M, Q is independently N or C—R3, one and only one of them having to be a N; 
         R3 is H; halogens; C1-C6 alkyls optionally substituted by halogens, hydroxy or C1-C6 alkoxy; 
         C1-C6 alkoxy optionally substituted by halogens, hydroxy or C1-C6 alkoxy; di-methyl-amino; 
         NH—C1-C6 alkyls optionally substituted by halogens, hydroxy or C1-C6 alkoxy; 
         and 
         wherein any H of the formula is H or its 2H or 3H isotope; any C of the general formula is C or its radioactive isotope 14C, or 11C; any F of the formula is F or its radioactive isotope 18F; any I of the formula is I or its radioactive isotope 123I, or 124I; 
         wherein any H of the formula is H or its 2H or 3H isotope; any C of the general formula is C or its radioactive isotope  14 C, or  11 C; any F of the formula is F or its radioactive isotope 18F; any I of the formula is I or its radioactive isotope 123I, or 124I; 
         provided that the compounds of formula I is not a compound selected from the group consisting of 
         2-(6-fluoropyridin-3-yl)-9H-pyrrolo [2,3-b:4,5-c′]dipyridine 
         2-[6-fluoro(2,4- 3 H 2 )pyridin-3-yl]-9H-pyrrolo[2,3-b:4,5-c′]dipyridine; 
         2-[6-fluoro(2- 3 H)pyridin-3-yl]-9H-pyrrolo[2,3-b:4,5-c′]dipyridine; 
         2-[6-fluoro(4- 3 H)pyridin-3-yl]-9H-pyrrolo[2,3-b:4,5-c′]dipyridine; and 
         and 2-[6-( 18 F)fluoropyridin-3-yl]-9H-pyrrolo[2,3-b:4,5-c′]dipyridine. 
       
     
     
         2 . A compound of formula I-A, or a pharmaceutically acceptable acid addition salt, a racemic mixture or its corresponding enantiomer and/or optical isomers thereof, 
       
         
           
           
               
               
           
         
         wherein 
         R1 is heterocyclyl selected from the group consisting of azetidine, pyrrolidine, piperidine and piperazine, optionally substituted by R2; or 
         heteroaromatics selected from the group consisting of pyrazole, furan, isoxazole, thiazole, pyridine, pyridine-2-one, pyrimidine, pyrazine, pyridazine optionally substituted by one or two substituents selected from halogen, C1-C6 alkyls optionally substituted by halogens or hydroxy or C1-C6 alkoxy, cyano, amino optionally substituted by C1-C6 alkyl optionally substituted by halogens, nitro, NHC(O)—C1-C6 alkyl, C(O)N—C1-C6 alkyl optionally substituted by halogens or hydroxy or C1-C6 alkoxy, C1-C6 alkoxy optionally substituted by halogens or hydroxy or C1-C6 alkoxy, a heterocyclyl group optionally substituted by halogens or C1-C6 alkyls optionally substituted by halogens; or 
         —NH—C(O)—R2; 
         R2 is heteroaromatics selected from the group consisting of pyrazole, furan, isoxazole, thiazole, pyridine, pyridine-2-one, pyrimidine, pyrazine, pyridazine optionally substituted by one or two substituents selected from halogen, C1-C6 alkyls optionally substituted by halogens or hydroxyl or C1-C6 alkoxy, cyano, amino, mono- or di-methyl-amino, nitro, NHC(O)—C1-C6 alkyl, C(O)N—C1-C6 alkyl optionally substituted by halogens or hydroxy or C1-C6 alkoxy, C1-C6 alkoxy optionally substituted by halogens or hydroxy or C1-C6 alkoxy, a heterocyclyl group; 
         A, M, Q is CR3; 
         R3 is H; halogens; C1-C6 alkyls optionally substituted by halogens, hydroxy or C1-C6 alkoxy; 
         C1-C6 alkoxy optionally substituted by halogens, hydroxy or C1-C6 alkoxy; di-methyl-amino; 
         NH—C1-C6 alkyls optionally substituted by halogens, hydroxy or C1-C6 alkoxy; and 
         and 
         wherein any H of the formula is H or its  2 H or  3 H isotope; any C of the general formula is C or its radioactive isotope  14 C, or  11 C; any F of the formula is F or its radioactive isotope  18 F; any I of the formula is I or its radioactive isotope  123 I, or  124 I; 
         provided that the compound of formula I-A is not 
         2-(6-fluoropyridin-3-yl)-9H-pyrrolo[2,3-b:4,5-c′]dipyridine; 
         2-[6-fluoro(2,4- 3 H 2 )pyridin-3-yl]-9H-pyrrolo[2,3-b:4,5-c′]dipyridine; 
         2-[6-fluoro(2- 3 H)pyridin-3-yl]-9H-pyrrolo[2,3-b:4,5-c′]dipyridine; 
         2-[6-fluoro(4- 3 H)pyridin-3-yl]-9H-pyrrolo[2,3-b:4,5-c′]dipyridine; or 
         and 2-[6-( 18 F)fluoropyridin-3-yl]-9H-pyrrolo[2,3-b:4,5-c′]dipyridine. 
       
     
     
         3 . A compound of formula I-B, or a pharmaceutically acceptable acid addition salt, a racemic mixture or its corresponding enantiomer and/or optical isomers thereof, 
       
         
           
           
               
               
           
         
         wherein 
         R1 is heterocyclyl selected from the group consisting of azetidine, pyrrolidine, piperidine and piperazine, optionally substituted by R2; or 
         heteroaromatics selected from the group consisting of pyrazole, furan, isoxazole, thiazole, pyridine, pyridine-2-one, pyrimidine, pyrazine, pyridazine optionally substituted by one or two substituents selected from halogen, C1-C6 alkyls optionally substituted by halogens or hydroxy or C1-C6 alkoxy, cyano, amino optionally substituted by C1-C6 alkyl optionally substituted by halogens, nitro, NHC(O)—C1-C6 alkyl, C(O)N—C1-C6 alkyl optionally substituted by halogens or hydroxy or C1-C6 alkoxy, C1-C6 alkoxy optionally substituted by halogens or hydroxy or C1-C6 alkoxy, a heterocyclyl group optionally substituted by halogens or C1-C6 alkyls optionally substituted by halogens; or 
         —NH—C(O)—R2; 
         R2 is heteroaromatics selected from the group consisting of pyrazole, furan, isoxazole, thiazole, pyridine, pyridine-2-one, pyrimidine, pyrazine, pyridazine optionally substituted by one or two substituents selected from halogen, C1-C6 alkyls optionally substituted by halogens or hydroxyl or C1-C6 alkoxy, cyano, amino, mono- or di-methyl-amino, nitro, NHC(O)—C1-C6 alkyl, C(O)N—C1-C6 alkyl optionally substituted by halogens or hydroxy or C1-C6 alkoxy, C1-C6 alkoxy optionally substituted by halogens or hydroxy or C1-C6 alkoxy, a heterocyclyl group; 
         R3 is H; halogens; C1-C6 alkyls optionally substituted by halogens, hydroxy or C1-C6 alkoxy; 
         C1-C6 alkoxy optionally substituted by halogens, hydroxy or C1-C6 alkoxy; di-methyl-amino; 
         NH—C1-C6 alkyls optionally substituted by halogens, hydroxy or C1-C6 alkoxy; and 
         wherein any H of the formula is H or its  2 H or  3 H isotope; any C of the general formula is C or its radioactive isotope  14 C, or  11 C; any F of the formula is F or its radioactive isotope  18 F; any I of the formula is I or its radioactive isotope  123 I, or  124 I. 
       
     
     
         4 . A compound of formula I-C, or a pharmaceutically acceptable acid addition salt, a racemic mixture or its corresponding enantiomer and/or optical isomers thereof, 
       
         
           
           
               
               
           
         
         wherein 
         R1 is heterocyclyl selected from the group consisting of azetidine, pyrrolidine, piperidine and piperazine, optionally substituted by R2; or 
         heteroaromatics selected from the group consisting of pyrazole, furan, isoxazole, thiazole, pyridine, pyridine-2-one, pyrimidine, pyrazine, pyridazine optionally substituted by one or two substituents selected from halogen, C1-C6 alkyls optionally substituted by halogens or hydroxy or C1-C6 alkoxy, cyano, amino optionally substituted by C1-C6 alkyl optionally substituted by halogens, nitro, NHC(O)—C1-C6 alkyl, C(O)N—C1-C6 alkyl optionally substituted by halogens or hydroxy or C1-C6 alkoxy, C1-C6 alkoxy optionally substituted by halogens or hydroxy or C1-C6 alkoxy, a heterocyclyl group optionally substituted by halogens or C1-C6 alkyls optionally substituted by halogens; or 
         —NH—C(O)—R2; 
         R2 is heteroaromatics selected from the group consisting of pyrazole, furan, isoxazole, thiazole, pyridine, pyridine-2-one, pyrimidine, pyrazine, pyridazine optionally substituted by one or two substituents selected from halogen, C1-C6 alkyls optionally substituted by halogens or hydroxyl or C1-C6 alkoxy, cyano, amino, mono- or di-methyl-amino, nitro, NHC(O)—C1-C6 alkyl, C(O)N—C1-C6 alkyl optionally substituted by halogens or hydroxy or C1-C6 alkoxy, C1-C6 alkoxy optionally substituted by halogens or hydroxy or C1-C6 alkoxy, a heterocyclyl group; 
         R3 is H; halogens; C1-C6 alkyls optionally substituted by halogens, hydroxy or C1-C6 alkoxy; 
         C1-C6 alkoxy optionally substituted by halogens, hydroxy or C1-C6 alkoxy; di-methyl-amino; 
         NH—C1-C6 alkyls optionally substituted by halogens, hydroxy or C1-C6 alkoxy; 
         and 
         wherein any H of the formula is H or its  2 H or  3 H isotope; any C of the general formula is C or its radioactive isotope  14 C, or  11 C; any F of the formula is F or its radioactive isotope  18 F; any I of the formula is I or its radioactive isotope  123 I, or  124 I. 
       
     
     
         5 . A compound of formula I-D, or a pharmaceutically acceptable acid addition salt, a racemic mixture or its corresponding enantiomer and/or optical isomers thereof, 
       
         
           
           
               
               
           
         
         wherein 
         R1 is heterocyclyl selected from the group consisting of azetidine, pyrrolidine, piperidine and piperazine, optionally substituted by R2; or 
         heteroaromatics selected from the group consisting of pyrazole, furan, isoxazole, thiazole, pyridine, pyridine-2-one, pyrimidine, pyrazine, pyridazine optionally substituted by one or two substituents selected from halogen, C1-C6 alkyls optionally substituted by halogens or hydroxy or C1-C6 alkoxy, cyano, amino optionally substituted by C1-C6 alkyl optionally substituted by halogens, nitro, NHC(O)—C1-C6 alkyl, C(O)N—C1-C6 alkyl optionally substituted by halogens or hydroxy or C1-C6 alkoxy, C1-C6 alkoxy optionally substituted by halogens or hydroxy or C1-C6 alkoxy, a heterocyclyl group optionally substituted by halogens or C1-C6 alkyls optionally substituted by halogens; or 
         —NH—C(O)—R2; 
         R2 is heteroaromatics selected from the group consisting of pyrazole, furan, isoxazole, thiazole, pyridine, pyridine-2-one, pyrimidine, pyrazine, pyridazine optionally substituted by one or two substituents selected from halogen, C1-C6 alkyls optionally substituted by halogens or hydroxyl or C1-C6 alkoxy, cyano, amino, mono- or di-methyl-amino, nitro, NHC(O)—C1-C6 alkyl, C(O)N—C1-C6 alkyl optionally substituted by halogens or hydroxy or C1-C6 alkoxy, C1-C6 alkoxy optionally substituted by halogens or hydroxy or C1-C6 alkoxy, a heterocyclyl group; 
         R3 is H; halogens; C1-C6 alkyls optionally substituted by halogens, hydroxy or C1-C6 alkoxy; 
         C1-C6 alkoxy optionally substituted by halogens, hydroxy or C1-C6 alkoxy; di-methyl-amino; 
         NH—C1-C6 alkyls optionally substituted by halogens, hydroxy or C1-C6 alkoxy; 
         and 
         wherein any H of the formula is H or its  2 H or  3 H isotope; any C of the general formula is C or its radioactive isotope  14 C, or  11 C; any F of the formula is F or its radioactive isotope  18 F; any I of the formula is I or its radioactive isotope  123 I, or  124 I. 
       
     
     
         6 . A compound according to  claim 1  wherein R1 is
 piperidine and piperazine, optionally substituted by R2; or 
 heteroaromatics selected from the group consisting of pyrazole, thiazole, pyridine, pyridine-2-one, pyrimidine, pyrazine, pyridazine optionally substituted by one or two substituents selected from fluorine, methyl or ethyl or propyl optionally substituted by fluorine or methoxy, cyano, amino optionally substituted by methyl or fluoro-ethyl, nitro, NHC(O)-methyl or ethyl or propyl optionally substituted by fluorine or methoxy, C(O)N-methyl or ethyl or propyl optionally substituted by fluorine or methoxy, methoxy or ethoxy or propoxy optionally substituted by fluorine or methoxy, a heterocyclyl group optionally substituted by fluorine or fluoromethyl. 
 
     
     
         7 . A compound according to  claim 6  wherein R1 is pyrazole, thiazole, pyridine, pyrimidine optionally substituted by one or two substituents selected from fluorine, methyl or ethyl or propyl optionally substituted by fluorine or methoxy, cyano, amino optionally substituted by methyl or fluoro-ethyl, nitro, C(O)N-methyl or ethyl or propyl optionally substituted by fluorine or methoxy, methoxy or ethoxy or propoxy optionally substituted by fluorine or methoxy; a morpholine or piperazine or piperidine, optionally substituted by fluorine or fluoromethyl. 
     
     
         8 . A compound according to  claim 1  wherein R2 is heteroaromatics selected from the group consisting of pyrazole, thiazole, pyridine, pyridine-2-one, pyrimidine, pyrazine, pyridazine optionally substituted by one or two substituents selected from fluorine, methyl or ethyl or propyl optionally substituted by fluorine or methoxy, cyano, amino, mono- or di-methyl-amino, nitro, NHC(O)-methyl or ethyl or propyl optionally substituted by fluorine or methoxy, C(O)N-methyl or ethyl or propyl optionally substituted by fluorine or methoxy, methoxy or ethoxy or propoxy optionally substituted by fluorine or methoxy, a heterocyclyl group. 
     
     
         9 . A compound according to  claim 8  wherein R2 is pyrazole, thiazole, pyridine, pyrimidine optionally substituted by one or two substituents selected from fluorine, methyl or ethyl or propyl optionally substituted by fluorine or methoxy, cyano, amino, mono- or di-methyl-amino, nitro, C(O)N-methyl or ethyl or propyl optionally substituted by fluorine or methoxy, methoxy or ethoxy or propoxy optionally substituted by fluorine or methoxy; a morpholine or piperazine. 
     
     
         10 . A compound according to  claim 1  wherein X is N, Y is CH and Z is CH. 
     
     
         11 . A compound according to  claim 1  wherein X is CH, Y is N, and Z is CH. 
     
     
         12 . A compound according to  claim 1  wherein A is CH, D is N, M is C—R3, and Q is CH. 
     
     
         13 . A compound according to  claim 1  wherein A is CH, D is N, M is CH, and Q is C—R3. 
     
     
         14 . A compound according to  claim 1  wherein A is CH, D is C—R3, M is N, and Q is CH. 
     
     
         15 . A compound according to  claim 1  wherein A is CH, D is CH, M is C—R3, and Q is N. 
     
     
         16 . A compound according to  claim 1  wherein R3 is H; fluorine; methyl or ethyl or propyl optionally substituted by fluorine, hydroxy or methoxy; methoxy or ethoxy or propoxy optionally substituted by fluorine or hydroxyl or methoxy; di-methyl-amino; NH-methyl or ethyl or propyl optionally substituted by fluorine, hydroxy or methoxy. 
     
     
         17 . A compound according to  claim 1  wherein any H of the general formula is H or its  2 H or  3 H isotope. 
     
     
         18 . A compound according to  claim 1  wherein C of the general formula on a benzylic methyl or a methoxy is C or is its radioactive isotope  14 C or  11 C. 
     
     
         19 . A compound according to  claim 1  wherein any F of the general formula is F or is its radioactive isotope  18 F. 
     
     
         20 . A compound according to  claim 1  wherein I of the general formula on an alkyl or aromatic or heteroaromatic position is I or its radioactive isotope  123 I, or  124 I. 
     
     
         21 . The compound according to  claim 2  which is
 2-(pyridin-4-yl)-9H-pyrrolo [2,3-b:4,5-c′]dipyridine, 
 2-(2-methoxypyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 2-(pyridin-3-yl)-9H-pyrrolo [2,3-b:4,5-c′]dipyridine, 
 2-(1-methyl-1H-pyrazol-4-yl)-9H-pyrrolo [2,3-b:4,5-c′]dipyridine, 
 2-(6-methoxypyridin-3-yl)-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 5-(9H-pyrrolo[2,3-b:4,5-c′]dipyridin-2-yl)pyridin-2(1H)-one, 
 2-(5-fluoro-6-methoxypyridin-3-yl)-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 2-(furan-3-yl)-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 2-(1H-pyrazol-4-yl)-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 2-[2-(morpholin-4-yl)pyrimidin-5-yl]-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 N-methyl-5-(9H-pyrrolo [2,3-b:4,5-c′]dipyridin-2-yl)pyridine-2-carboxamide, 
 3-fluoro-5-(9H-pyrrolo[2,3-b:4,5-c′]dipyridin-2-yl)pyridin-2-amine, 
 2-[4-(pyrimidin-2-yl)piperazin-1-yl]-9H-pyrrolo [2,3-b:4,5-c′]dipyridine, 
 2-[4-(pyridin-4-yl)piperazin-1-yl]-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 2-(1H-pyrazol-3-yl)-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 4-(9H-pyrrolo [2,3-b:4,5-c′]dipyridin-2-yl)pyridin-2-amine, 
 4-(9H-pyrrolo[2,3-b:4,5-c′]dipyridin-2-yl)pyridin-2(1H)-one, 
 2-(5-fluoropyridin-2-yl)-9H-pyrrolo [2,3-b:4,5-c′]dipyridine, 
 2-fluoro-5-(9H-pyrrolo[2,3-b:4,5-c′]dipyridin-2-yl)pyridin-3-amine, 
 N-methyl-5-(9H-pyrrolo [2,3-b:4,5-c′]dipyridin-2-yl)pyrimidin-2-amine, 
 2-[6-(morpholin-4-yl)pyridin-3-yl]-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 N-(2-methoxyethyl)-5-(9H-pyrrolo[2,3-b:4,5-c′]dipyridin-2-yl)pyrimidin-2-amine, 
 2-[2-(piperazin-1-yl)pyrimidin-5-yl]-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 2-(5-methyl-1H-pyrazol-3-yl)-9H-pyrrolo [2,3-b:4,5-c′]dipyridine, 
 2-[1-(2-fluoroethyl)-1H-pyrazol-4-yl]-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 N-methyl-2-[4-(9H-pyrrolo [2,3-b:4,5-c′]dipyridin-2-yl)-1H-pyrazol-1-yl]acetamide 
 N-methyl-6-(9H-pyrrolo [2,3-b:4,5-c′]dipyridin-2-yl)pyridine-3-carboxamide, 
 N,N-dimethyl-5-(9H-pyrrolo[2,3-b:4,5-c′]dipyridin-2-yl)pyridine-2-carboxamide, 
 N-(2-fluoroethyl)-5-(9H-pyrrolo [2,3-b:4,5-c′]dipyridin-2-yl)pyridine-2-carboxamide, 
 N-(2-methoxyethyl)-5-(9H-pyrrolo[2,3-b:4,5-c′]dipyridin-2-yl)pyridine-2-carboxamide, 
 2-(4-methoxy-1H-pyrazol-1-yl)-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 2-[2-(morpholin-4-yl)-1,3-thiazol-5-yl]-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 1-{4-[5-(9H-pyrrolo[2,3-b: 4,5-c′]dipyridin-2-yl)pyrimidin-2-yl]piperazin-1-yl}ethanone, 
 6-fluoro-N-(9H-pyrrolo[2,3-b:4,5-c′]dipyridin-2-yl)pyridine-3-carboxamide, 
 6-(methylamino)-N-(9H-pyrrolo [2,3-b:4,5-c′]dipyridin-2-yl)pyridine-3-carboxamide, 
 2-(6-fluoropyridin-3-yl)-7-methoxy-9H-pyrrolo [2,3-b:4,5-c′]dipyridine, 
 5-(7-methoxy-9H-pyrrolo[2,3-b:4,5-c′]dipyridin-2-yl)-N-methylpyridine-2-carboxamide, 
 7-methoxy-2-(1-methyl-1H-pyrazol-4-yl)-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 7-methoxy-2-[2-(morpholin-4-yl)pyrimidin-5-yl]-9H-pyrrolo [2,3-b:4,5-c′]dipyridine, 
 6-(7-methoxy-9H-pyrrolo[2,3-b:4,5-c′]dipyridin-2-yl)-N-methylpyridine-3-carboxamide, 
 5-(7-methoxy-9H-pyrrolo[2,3-b:4,5-c′]dipyridin-2-yl)pyrimidine-2-carbonitrile, 
 2-(6-fluoropyridin-3-yl)-N,N-dimethyl-9H-pyrrolo[2,3-b:4,5-c′]dipyridin-7-amine, 5-[7-(dimethylamino)-9H-pyrrolo[2,3-b:4,5-c′]dipyridin-2-yl]-N-methylpyridine-2-carboxamide 
 N,N-dimethyl-2-(1-methyl-1H-pyrazol-4-yl)-9H-pyrrolo[2,3-b:4,5-c′]dipyridin-7-amine, 
 2-(6-fluoropyridin-3-yl)-7-methyl-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 N-methyl-5-(7-methyl-9H-pyrrolo [2,3-b:4,5-c′]dipyridin-2-yl)pyridine-2-carboxamide, 
 7-methyl-2-(1-methyl-1H-pyrazol-4-yl)-9H-pyrrolo [2,3-b:4,5-c′]dipyridine, 
 2-(6-fluoropyridin-3-yl)-7-(methoxymethyl)-9H-pyrrolo [2,3-b:4,5-c′]dipyridine, 
 5-[7-(methoxymethyl)-9H-pyrrolo[2,3-b:4,5-c′]dipyridin-2-yl]-N-methylpyridine-2-carboxamide, 
 7-(methoxymethyl)-2-(1-methyl-1H-pyrazol-4-yl)-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 2-[6-fluoro(2- 3 H)pyridin-3-yl](5,7- 3 H 2 )-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 2-[6-fluoro(2- 2 H)pyridin-3-yl](5,7- 2 H 2 )-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 2-(6-fluoropyridin-3-yl)(3- 2 H)-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 2-(6-fluoropyridin-3-yl)(8- 2 H)-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 2-[6-fluoro(5- 2 H)pyridin-3-yl]-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, 
 N-methyl-5-[(5,7- 3 H 2 )-9H-pyrrolo [2,3-b:4,5-c′]dipyridin-2-yl](6- 3 H)pyridine-2-carboxamide, or 
 2-[1-methyl(3- 3 H)-1H-pyrazol-4-yl](5,7- 3 H 2 )-9H-pyrrolo[2,3-b:4,5-c′]dipyridine. 
 
     
     
         22 . A compound according to  claim 3  which is
 2-(6-fluoropyridin-3-yl)-9H-pyrrolo[2,3-b: 5,4-c′]dipyridine, 
 N-methyl-5-(9H-pyrrolo [2,3-b:5,4-c′]dipyridin-2-yl)pyridin-2-amine, 
 2-(1H-pyrazol-4-yl)-9H-pyrrolo[2,3-b:5,4-c′]dipyridine, 
 2-(1-methyl-1H-pyrazol-4-yl)-9H-pyrrolo [2,3-b:5,4-c′]dipyridine, 
 N-methyl-5-(9H-pyrrolo [2,3-b:5,4-c′]dipyridin-2-yl)pyridine-2-carboxamide, 
 2-(4-methoxy-1H-pyrazol-1-yl)-9H-pyrrolo[2,3-b:5,4-c′]dipyridine or 
 2-[6-fluoro(2- 3 H)pyridin-3-yl](6,8- 3 H 2 )-9H-pyrrolo[2,3-b:5,4-c′]dipyridine. 
 
     
     
         23 . The compound according to  claim 4  which is
 2-(6-fluoropyridin-3-yl)-9H-pyrrolo[2,3-b:5,4-b′]dipyridine or 
 2-[4-(3-fluoropropyl)piperidin-1-yl]-9H-pyrrolo [2,3-b:5,4-b′]dipyridine. 
 
     
     
         24 . The compound according to  claim 5  which is
 7-(1-methyl-1H-pyrazol-4-yl)-9H-pyrrolo [2,3-b:4,5-c′]dipyridine, 
 7-(6-fluoropyridin-3-yl)-9H-pyrrolo[2,3-b:4,5-c′]dipyridine, or 
 N-methyl-5-(9H-pyrrolo [2,3-b:4,5-c′]dipyridin-7-yl)pyridine-2-carboxamide. 
 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . A pharmaceutical composition comprising a compound according to  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         29 . A method of diagnosing or monitoring tau aggregates in the brain of a subject, the method comprising administering a radiolabeled compound containing an isotope according to  claim 1  to the subject. 
     
     
         30 . A method of treating a subject with a neurodegenerative disease in which tau aggregates in the brain are implicated, the method comprising administering to the subject an effective amount of compound according to  claim 1 .