Bicyclic heterocycle derivatives and use thereof as GPR119 modulators
View Patent ↗The present invention relates to Bicyclic Heterocycle Derivatives of Formula (I), compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of a G-protein coupled receptor (GPCR) such as GPR119 in a patient.
1. A compound having the formula
or a pharmaceutically acceptable salt thereof, wherein:
A is O;
B is:
J and M are each —N— and L is —CH;
Q is a bond;
X—Y is CH 2 —CH 2 or CH═CH;
W is —C(O)O—, —C(O)— or —S(O) 2 —;
R 3 is alkyl, haloalkyl or cycloalkyl, wherein the cycloalkyl group can be optionally substituted with up to 4 substituents, each independently selected from alkyl and halo; and
R 8 is (i) phenyl optionally substituted with up to 2 groups independently selected from halo, —CN and —S(O) 2 -alkyl, or (ii) a heteroaryl optionally substituted with up to 2 groups independently selected from alkyl and heteroaryl.
2. The compound of claim 1 , where W is —C(O)O—.
3. The compound of claim 1 where R 8 is phenyl, optionally substituted with up to 2 groups each independently selected from halo, —CN, and —S(O) 2 -alkyl.
4. The compound of claim 1 having the structure:
or a pharmaceutically acceptable salt thereof.
5. A composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
6. A method for treating type 2 diabetes in a patient, the method comprising administering to the patient an effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof.
7. A compound having the formula
or a pharmaceutically acceptable salt thereof, wherein:
A is O;
B is:
J and M are each —N— and L is —CH;
Q is a bond;
X—Y is CH 2 —CH 2 or CH═CH;
W is —C(O)O—, —C(O)— or —S(O) 2 —;
R 3 is alkyl, haloalkyl or cycloalkyl, wherein the cycloalkyl group can be optionally substituted with up to 4 substituents, each independently selected from alkyl and halo; and
R 8 is (i) phenyl optionally substituted with up to 2 groups independently selected from halo, —CN and —S(O) 2 -alkyl, or (ii) a heteroaryl optionally substituted with up to 2 groups independently selected from alkyl and heteroaryl.
8. The compound of claim 7 , where W is —C(O)O—.
9. The compound of claim 7 , where W is —S(O) 2 —.
10. The compound of claim 7 where R 8 is phenyl, optionally substituted with up to 2 groups each independently selected from halo, —CN, and —S(O) 2 -alkyl.
11. The compound of claim 7 where R 8 is pyridyl, optionally substituted with up to 2 groups each independently selected from alkyl and heteroaryl.
12. The compound of claim 7 having the structure:
or a pharmaceutically acceptable salt thereof.
13. A composition comprising the compound of claim 7 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
14. A method for treating type 2 diabetes in a patient, the method comprising administering to the patient an effective amount of the compound of claim 7 , or a pharmaceutically acceptable salt thereof.
15. A compound having the formula
or a pharmaceutically acceptable salt thereof, wherein:
A is O;
B is:
J and M are each —N— and L is —CH;
Q is a bond;
X—Y is CH 2 —CH 2 or CH═CH;
W is —C(O)O—, —C(O)— or —S(O) 2 —;
R 3 is alkyl, haloalkyl or cycloalkyl, wherein the cycloalkyl group can be optionally substituted with up to 4 substituents, each independently selected from alkyl and halo; and
R 8 is (i) phenyl optionally substituted with up to 2 groups independently selected from halo, —CN and —S(O) 2 -alkyl, or (ii) a heteroaryl optionally substituted with up to 2 groups independently selected from alkyl and heteroaryl.
16. The compound of claim 15 , where W is —C(O)O—.
17. The compound of claim 15 where R 8 is phenyl, optionally substituted with up to 2 groups each independently selected from halo, —CN, and —S(O) 2 -alkyl.
18. A composition comprising the compound of claim 15 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
19. A method for treating type 2 diabetes in a patient, the method comprising administering to the patient an effective amount of the compound of claim 15 , or a pharmaceutically acceptable salt thereof.