1-aryl-3-azabicyclo[3.1.0]hexanes: preparation and use to treat neuropsychiatric disorders
The invention provides novel, multiply-substituted 1-aryl-3-azabicyclo[3.1.0]hexanes, and related processes and intermediates for preparing these compounds, as well as compositions and methods employing these compounds for the treatment and/or prevention of central nervous system (CNS) disorders, including depression and anxiety.
1. A method for treating a central nervous system (CNS) disorder in a mammalian subject in need thereof comprising administering to the mammalian subject in need thereof an effective amount of 1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof.
2. The method according to claim 1 wherein the mammalian subject is human.
3. The method according to claim 2 wherein the CNS disorder is depression.
4. The method according to claim 1 wherein the CNS disorder is an anxiety disorder.
5. The method according to claim 2 wherein the CNS disorder is an anxiety disorder.
6. The method according to claim 1 wherein the effective amount of 1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or pharmaceutically acceptable salt thereof is an effective amount of (1R,5S)-1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof.
7. The method according to claim 2 wherein the effective amount of 1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or pharmaceutically acceptable salt thereof is an effective amount of (1R,5S)-1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof.
8. The method according to claim 3 wherein the effective amount of 1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or pharmaceutically acceptable salt thereof is an effective amount of (1R,5S)-1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof.
9. The method according to claim 4 wherein the effective amount of 1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or pharmaceutically acceptable salt thereof is an effective amount of (1R,5S)-1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof.
10. The method according to claim 5 wherein the effective amount of 1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or pharmaceutically acceptable salt thereof is an effective amount of (1R,5S)-1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof.
11. The method according to claim 2 wherein the CNS disorder is attention deficit hyperactivity disorder (ADHD).
12. The method according to claim 11 wherein the effective amount of 1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or pharmaceutically acceptable salt thereof is an effective amount of (1R,5S)-1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof.
13. A method for treating a central nervous system (CNS) disorder in a mammalian subject in need thereof comprising administering to the mammalian subject in need thereof an effective amount of a pharmaceutical composition comprising 1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or vehicle therefor.
14. The method according to claim 13 wherein the mammalian subject is human.
15. The method according to claim 14 wherein the CNS disorder is depression.
16. The method according to claim 13 wherein the CNS disorder is an anxiety disorder.
17. The method according to claim 14 wherein the CNS disorder is an anxiety disorder.
18. The method according to claim 13 wherein the 1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or pharmaceutically acceptable salt thereof is (1R,5S)-1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof.
19. The method according to claim 14 wherein the 1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or pharmaceutically acceptable salt thereof is (1R,5S)-1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof.
20. The method according to claim 15 wherein the 1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or pharmaceutically acceptable salt thereof is (1R,5S)-1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof.
21. The method according to claim 16 wherein the 1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or pharmaceutically acceptable salt thereof is (1R,5S)-1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof.
22. The method according to claim 17 wherein the 1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or pharmaceutically acceptable salt thereof is (1R,5S)-1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof.
23. The method according to claim 13 wherein the CNS disorder is attention deficit hyperactivity disorder (ADHD).
24. The method according to claim 23 wherein the 1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or pharmaceutically acceptable salt thereof is (1R,5S)-1-(naphthalen-2-yl)-3-aza-bicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof.