9-azabicyclo[3.3.1]nonane derivatives
View Patent ↗The present invention relates to a 9-azabicyclo[3.3.1]nonane derivative of formula I, wherein each of the substituents is given the definition as set forth in the specification and claims, or a pharmaceutically acceptable salt or solvate thereof. The invention also relates to pharmaceutical compositions comprising said 9-azabicyclo[3.3.1]nonane derivatives and to their use in therapy.
1. A 9-azabicyclo[3.3.1]nonane of formula I,
wherein
R 1 is H or C 1-5 alkyl;
X is O, wherein R 2 is H, C 1-5 alkyl or C 2-5 acyl and
Ar is a heteroaryl ring selected from benzothienyl and benzoisothiazolyl, both being optionally substituted with one to three of R 3 -R 5 independently selected from halogen, C 1-5 alkyl, C 1-5 alkoxy, C 3-6 cycloalkyl, C 2-5 alkenyl, C 2-5 alkynyl, CN, NO 2 , hydroxy, phenyl, phenoxy and phenylC 1-2 alkoxy, wherein said C 1-5 alkyl and C 1-5 alkoxy are optionally substituted with one to three halogens and wherein said phenyl, phenoxy and phenylC 1-2 alkoxy are optionally substituted with one to three substituents independently selected from halogen and methyl or two of R 3 -R 5 at adjacent positions together form a methylenedioxy or propylene unit,
or a pharmaceutically acceptable salt thereof.
2. The 9-azabicyclo[3.3.1]nonane according to claim h wherein R 1 is H or methyl.
3. The 9-azabicyclo[3.3.1]nonane according to claim 1 , wherein Ar is benzothienyl optionally substituted with 1-2 substituents independently selected from chloro, fluoro, methyl and cyano.
4. The 9-azabicyclo[3.3.1]nonane according to claim 2 , wherein Ar is benzothienyl optionally substituted with 1-2 substituents independently selected from chloro, fluoro, methyl and cyano.
5. A 9-azabicyclo[3.3.1]nonane selected from:
exo-3-(benzo[d]isothiazol-7-yloxy)-9-azabicyclo[3.3.1]nonane;
exo-3-(benzo[d]isothiazol-4-yloxy)-9-azabicyclo[3.3.1]nonane;
exo-3-(3-chloro-2-fluorophenoxy)-9-azabicyclo[3.3.1]nonane;
exo-3-(benzo[b]thiophen-7-yloxy)-9-azabicyclo[3.3.1]nonane;
exo-3-(benzo[b]thiophen-6-yloxy)-9-azabicyclo[3.3.1]nonane;
exo-3-(benzo[b]thiophen-4-yloxy)-9-azabicyclo[3.3.1]nonane;
exo-3-(3,4-dichloropyridin-2-yloxy)-9-azabicyclo[3.3.1]nonane;
exo-3-(5,6-dichloropyridin-2-yloxy)-9-azabicyclo[3.3.1]nonane;
exo-3-(4,6-dichloropyridin-2-yloxy)-9-azabicyclo[3.3.1]nonane;
exo-3-(3-fluoro-4-methylphenoxy)-9-azabicyclo[3.3.1]nonane;
exo-3-(2,3-dichlorophenoxy)-9-azabicyclo[3.3.1]nonane;
exo-3-(9-azabicyclo[3.3.1]non-3 yloxy)benzonitrile;
exo-3-(3,5-dichlorophenoxy)-9-azabicyclo[3.3.1]nonane and
exo-3-(3-prop-1-ynylphenoxy)-9-azabicyclo[3.3.1]nonane
or a pharmaceutically acceptable salt thereof.
6. A pharmaceutical composition comprising a 9-azabicyclo[3.3.1]nonane or a pharmaceutically acceptable salt thereof according to claim 1 in admixture with one or more pharmaceutically acceptable excipients.
7. The 9-azabicyclo[3.3.1]nonane according to claim 1 , wherein Ar is benzoisothiazolyl optionally substituted with 1-2 substituents independently selected from chloro, fluoro, methyl and cyano.
8. The 9-azabicyclo[3.3.1]nonane according to claim 2 , wherein Ar is benzoisothiazolyl optionally substituted with 1-2 substituents independently selected from chloro, fluoro, methyl and cyano.