8-Azabicyclo[3.2.1]octane derivatives

• US 20070185156A1
• Filed: 12/01/2006
• Published: 08/09/2007
• Est. Priority Date: 12/01/2005
• Status: Active Grant

• Current Assignee: Merck Sharp & Dohme BV (Merck & Co., Inc.)
• Original Assignee: N.V. Organon (Merck & Co., Inc.)
• Inventors: Bingham, Matilda, Napier, Susan, Dunbar, Neil
• Granted Patent: US 7,605,170 B2
• Time in Patent Office: Days
• US Class Current: 514/304
• CPC Class Codes: C07D 451/02 containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
• CPC Class Codes: C07D 451/06 Oxygen atoms

Abstract

The present invention relates to a 8-azabicyclo[3.2.1]octane 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 thereof or solvate thereof. The present invention also relates to a pharmaceutical composition comprising an 8-azabicyclo[3.2.1]octane derivative in admixture with one or more pharmaceutically acceptable auxiliaries and to the use of the 8-azabicyclo[3.2.1]octane derivative in therapy.

Claims

1. A 8-azabicyclo[3.2.1]octane derivative of Formula I,

2. The 8-azabicyclo[3.2.1]octane derivative according to claim 1, wherein R¹ is H or methyl.

3. The 8-azabicyclo[3.2.1]octane derivative according to claim 1, wherein n is 0.

4. The 8-azabicyclo[3.2.1]octane derivative according to claim 1, wherein Y is O and n is 1.

5. The 8-azabicyclo[3.2.1]octane derivative according to claim 1, wherein Ar¹ is phenyl or pyridyl optionally substituted with 1-2 substituents selected from chloro, fluoro, methyl, methoxy or CN.

6. The 8-azabicyclo[3.2.1]octane derivative according to claim 1, wherein Ar² is phenyl or pyridyl optionally substituted with 1-2 substituents selected from chloro, fluoro, methyl, methoxy, CN or CF₃.

8. A pharmaceutical composition comprising a 8-azabicyclo[3.2.1]octane derivative according to claim 1 in admixture with one or more pharmaceutically acceptable auxiliaries.

9. A method of treating or preventing a disease or disorder in a mammal which is responsive to monoamine neurotransmitter reuptake in the nervous system, the method comprising administering to the mammal an effective amount of the 8-azabicyclo[3.2.1]octane derivative according to claim 1.

10. The method according to claim 9, wherein the disorder is depression or pain.

11. The method according to claim 9, wherein the mammal is a human.

7. A 8-azabicyclo[3.2.1]octane derivative selected from:

3-exo-(5-chlorobiphenyl-3-yloxy)-8-azabicyclo[3.2.1]octane;

exo 5-(8-azabicyclo[3.2.1]oct-3-yloxy)biphenyl-3-carbonitrile;

exo 3-(8-azabicyclo[3.2.1]oct-3-yloxy)-5-phenoxybenzonitrile;

3-exo-(4′

-methoxybiphenyl-3-yloxy)-8-azabicyclo[3.2.1]octane;

exo 3′

-(8-azabicyclo[3.2.1]oct-3-yloxy)biphenyl-4-carbonitrile;

3-exo-(3-pyridin-4-ylphenoxy)-8-azabicyclo[3.2.1]octane;

exo 2-{6-(8-azabicyclo[3.2.1]oct-3-yloxy)-4-chloropyridin-2-yl}benzonitrile;

exo 2-(8-azabicyclo[3.2.1]oct-3-yloxy)-6-(2-cyanophenyl)isonicotinonitrile;

exo 3-[(8-azabicyclo[3.2.1]oct-3-yl)oxy]-5-(3-chloropyridin-2-yl)benzonitrile;

exo 3-(8-azabicyclo[3.2.1]oct-3-yloxy)-5-cyanophenyl)nicotinonitrile;

exo 3-(8-azabicyclo[3.2.1]oct-3-yloxy)-5-(3-fluoropyridin-2-yl)benzonitrile;

exo 3′

-(8-azabicyclo[3.2.1]oct-3-yloxy)biphenyl-2-carbonitrile;

exo 2-[6-(8-azabicyclo[3.2.1]oct-3-yloxy)pyridin-2-yl]benzonitrile;

3′

-(8-azabicyclo[3.2.1]oct-3-exo-yloxy)-2′

-fluorobiphenyl-4-carbonitrile and

2-(8-azabicyclo[3.2.1]oct-3-exo-yloxy)-6-phenylisonicotinonitrile

or a pharmaceutically acceptable salt or solvate thereof.