9H-pyrrolo-dipyridine derivatives
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 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, and
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, or
a radiolabelled version thereof, wherein the radiolabelled version contains at least one 2 H or 3 H isotope in place of hydrogen; at least one 14 C or 11 C isotope in place of C; at least one 18 F isotope for F in place of F; or at least one 123 I or 124 I isotope in place of I.
2. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable excipient.
3. 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.
4. 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 .