Somatostatin receptor subtype 4 (SSTR4) agonists
3-aza-bicyclo[3.1.0]hexane-6-carboxylic acid amide derivatives which are agonists of somatostatin receptor subtype 4 (SSTR4), useful for preventing or treating medical disorders related to SSTR4.
1. A method for the treatment of pain selected from the group consisting of visceral pain, phantom limb pain, stump pain, and pain due to rheumatoid arthritis, which comprises administering to a host suffering from said pain a therapeutically effective amount of a compound of Formula I to treat the pain, wherein Formula I is represented by:
or a salt thereof, wherein:
A is selected from the group consisting of H and C 1-6 -alkyl;
R 1 and R 2 are independently selected from the group consisting of H, C 1-6 -alkyl and C 3-6 -cycloalkyl, wherein at least one of R 1 or R 2 is C 1-6 -alkyl or C 3-6 -cycloalkyl, and the C 1-6 -alkyl or the C 3-6 -cycloalkyl is optionally substituted with halogens or MeO—;
W is a mono- or bicyclic heteroaryl, each of which is optionally substituted with one or more R 3 , and wherein the heteroaryl comprises up to 4 heteroatoms and one or two 5- or 6-membered ring(s);
R 3 is independently selected from the group consisting of C 1-6 -alkyl, C 1-6 -alkyl-O—, halogen, HO—, and NC—; and
Y is selected from the group consisting of a bond, —CH 2 —, —CH 2 CH 2 —, and —CH 2 O—.
2. The method of claim 1 , wherein A is H; and R 1 and R 2 are C 1-6 alkyl.
3. The method of claim 2 , wherein Y is —CH 2 O—and W is
optionally substituted with one R 3 .
4. The method of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
5. The method of claim 1 , wherein the compound is a pharmaceutically acceptable salt of
6. The method of claim 1 , wherein the compound is
7. The method of claim 3 , wherein the pain is visceral pain.
8. The method of claim 4 , wherein the pain is visceral pain.
9. The method of claim 3 , wherein the pain is phantom limb pain.
10. The method of claim 4 , wherein the pain is phantom limb pain.
11. The method of claim 4 , wherein the pain is stump pain.
12. The method of claim 3 , wherein the pain is pain due to rheumatoid arthritis.
13. The method of claim 4 , wherein the pain is pain due to rheumatoid arthritis.
14. The method of claim 1 , wherein the host is a human being.
15. The method of claim 8 , wherein the host is a human being.
16. The method of claim 10 , wherein the host is a human being.
17. The method of claim 13 , wherein the host is a human being.
18. A method for the treatment of headache, which comprises administering to a human being suffering from headache an effective amount of a compound of Formula I to treat the headache, wherein Formula I is represented by:
or a salt thereof, wherein:
A is selected from the group consisting of H and C 1-6 -alkyl;
R 1 and R 2 are independently selected from the group consisting of H, C 1-6 -alkyl and C 3-6 -cycloalkyl, wherein at least one of R 1 or R 2 is C 1-6 -alkyl or C 3-6 -cycloalkyl, and the C 1-6 -alkyl or the C 3-6 -cycloalkyl is optionally substituted with halogens or MeO—;
W is a mono- or bicyclic heteroaryl, each of which is optionally substituted with one or more R 3 , and wherein the heteroaryl comprises up to 4 heteroatoms and one or two 5- or 6-membered ring(s);
R 3 is independently selected from the group consisting of C 1-6 -alkyl, C 1-6 -alkyl-O—, halogen, HO—, and NC—; and
Y is selected from the group consisting of a bond, —CH 2 —, —CH 2 CH 2 —, and —CH 2 O—.
19. The method of claim 18 , wherein A is H; and R 1 and R 2 are C 1-6 alkyl.
20. The method of claim 19 , wherein Y is —CH 2 O—; and W is
optionally substituted with one R 3 .
21. The method of claim 18 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
22. The method of claim 18 , wherein the compound is a pharmaceutically acceptable salt of
23. The method of claim 18 , wherein the compound is
24. The method of claim 18 , wherein the headache is migraine.
25. The method of claim 21 , wherein the headache is migraine.