Diazacarbazole derivatives as tau-PET-ligands

1. A compound of Formula I

wherein

R is hydrogen or tritium;

F is fluoro or 18 fluoro;

or a pharmaceutically acceptable acid addition salt thereof.

2. The compound of Formula I according to claim 1 , selected from the group consisting of

2-(6-fluoro-pyridin-3-yl)-9H-dipyrido[2,3-b;3′,4′-d]pyrrole,

3 H-2-(6-fluoro-pyridin-3-yl)-9H-dipyrido[2,3-b;3′,4′-d]pyrrole and

and [18F]-2-(6-fluoro-pyridin-3-yl)-9H-dipyrido[2,3-b;3′,4′-d]pyrrole.

or a pharmaceutically acceptable acid addition salt thereof.

3. A process for the manufacture of a compound of Formula I as defined in claim 1 or a pharmaceutically acceptable acid addition salt thereof, comprising one of the following three methods, a)-c):

a) coupling a compound of Formula 2 (X=Cl, Br)

with a boronic acid or boronic acid ester of Formula 3

wherein R′ is hydrogen or lower alkyl,

thus producing the following compound of Formula I, called Compound A

wherein R is hydrogen,

and, optionally, converting Compound A into a pharmaceutically acceptable acid addition salt or into a compound of Formula I, wherein R is tritium by bombarding Compound A with tritium gas in the presence of a catalyst selected from iridium, ruthenium, rhodium and palladium containing complexes, in a solvent selected from dichloromethane, chlorobenzene, DMF and DMSO or mixtures thereof;

or

b) coupling a compound of Formula 4

with a fluorinating reagent selected from potassium fluoride and tetrabutylammonium fluoride,

thus producing Compound A of Formula I

wherein R is hydrogen,

and, optionally, converting Compound A into a pharmaceutically acceptable acid addition salt or into a compound of Formula I, wherein R is tritium by bombarding Compound A with tritium gas in the presence of a catalyst selected from iridium, ruthenium, rhodium and palladium containing complexes, in a solvent selected from dichloromethane, chlorobenzene, DMF and DMSO or mixtures thereof;

or

c) reacting a compound of Formula I

wherein R is hydrogen, with tritium gas in the presence of a catalyst selected from iridium, ruthenium, rhodium and palladium containing complexes, in a solvent selected from dichloromethane, chlorobenzene, DMF and DMSO or mixtures thereof, thus producing the following compound of Formula I, called Compound B

wherein R is tritium, and, optionally, converting Compound B into a pharmaceutically acceptable acid addition salt.

4. A pharmaceutical preparation comprising a compound of Formula I according to claim 1 or a pharmaceutically acceptable acid addition salt thereof, and a pharmaceutical acceptable carrier.

5. A method of diagnostic imaging tau-aggregate deposits, beta-amyloid aggregate deposits, or alpha-synuclein aggregate deposits, comprising

introducing into a mammal a detectable quantity of the preparation according to claim 4 ;

and

detecting the compound bound to one or more deposits selected from tau-aggregate deposits, beta-amyloid aggregate deposits, or alpha-synuclein aggregate deposits via diagnostic imaging.

6. The method of claim 5 , wherein the deposits are tau-aggregate deposits.