N-substituted-azacyclylamines as histamine-3 antagonists

Abstract

The present invention provides a compound of formula I and the use thereof for the treatment of a central nervous system disorder related to or affected by the histamine-3 receptor.

Description

Claims

1. A compound of formula I

2. The compound according to claim 1 wherein X is CO or CH2.

3. The compound according to claim 1 wherein n is 1 and p is 1 or 2.

4. The compound according to claim 1 wherein R8 and R9 are each independently H or methyl.

5. The compound according to claim 2 wherein R1 and R2 are taken together with the atom to which they are attached to form a 5-membered ring.

6. The compound according to claim 2 wherein R3 is NR4R5 or an optionally substituted indole, indazole, phenyl or benzimidazole ring.

7. The compound according to claim 3 wherein X is CO or CH2 and R1 and R2 are taken together with the atom to which they are attached to form a 5-membered ring.

8. The compound according to claim 7 wherein R3 is NR4R5 or an optionally substituted benzimidazole ring attached at the 2-position of said benzimidazole ring; and R4 and R5 are taken together with the atom to which they are attached to form an optionally substituted indole, indazole or benzimidazole ring.

9. The compound according to claim 1 selected from the group consisting essentially of:

10. A method for the treatment of a central nervous system disorder related to or affected by the Histamine-3 receptor in a patient in need thereof which comprises providing to said patient a therapeutically effective amount of a compound of formula I

11. The method according to claim 10 wherein said disorder is a cognitive disorder, a developmental disorder or a sleep disorder.

12. The method according to claim 11 wherein said disorder is a cognitive disorder.

13. The method according to claim 11 wherein said disorder is selected from the group consisting of: Alzheimer's disease; a learning disorder; attention deficit disorder; and schizophrenia.

14. A method for the inhibition of the H3 receptor which comprises contacting said receptor with an effective amount of a compound of formula I

15. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and an effective amount of a compound of formula I

16. The composition according to claim 15 having a formula I compound wherein X is CO or CH2.

17. The composition according to claim 16 having a formula I compound wherein n is 1; p is 1 or 2; R1 and R2 are taken together with the atom to which they are attached to form a 5-membered ring; and R3 is NR4R5 or an optionally substituted indole, indazole, or benzimidazole ring.

18. The composition according to claim 17 having a formula I compound wherein R3 is NR4R5 and R4 and R5 are taken together with the atom to which they are attached to form an optionally substituted indole, indazole or benzimidazole ring.

19. The composition according to claim 15 having a formula I compound selected from the group consisting of:

20. A process for the preparation of a compound of formula I