Bicyclic heterocycle derivatives and methods of use thereof
View Patent ↗The present invention relates to Bicyclic Heterocycle Derivatives, 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 GPCR in a patient.
1. A compound having the formula:
or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
R 1 is cycloalkyl, which can be unsubstituted or optionally substituted with an alkyl or halo group;
R 2 is H, alkyl, halo or —O-alkyl;
R 3 is alkyl, cycloalkyl, aryl or heteroaryl, wherein any R 3 group can be unsubstituted or optionally substituted with R 4 ;
each occurrence of R 4 represents 1 to 4 substituents, which can be the same or different, and which are selected from alkyl, halo, —CN, —OR 5 , haloalkyl, aryl, heteroaryl, heterocycloalkyl, cycloalkyl, —N(R 5 ) 2 , —S(O) 2 R 6 , —C(O)R 5 , —C(O)OR 5 or —C(O)N(R 5 ) 2 ;
each occurrence of R 5 is independently H, alkyl or aryl;
each occurrence of R 6 is independently alkyl, aryl, haloalkyl, cycloalkyl, heterocycloalkyl or heteroaryl;
each occurrence of R 7 is independently H, alkyl, halo, —CN, —O-alkyl or haloalkyl;
each occurrence of R 8 is independently H or alkyl;
J is —C(R 7 )— or —N—;
K is —C(R 7 )— or —N—;
L is —C(R 7 )— or —N—;
Q is arylene or heteroarylene, each of which can be unsubstituted or optionally substituted with R 4 ;
W is a bond, alkylene, —C(O)—, —C(O)O—, —C(O)NH— or —S(O) 2 —;
Y is alkylene, —O— or —N(R 5 )—;
Z is alkylene, —O— or —N(R 5 )—;
p is 0, 1 or 2;
q is 1, 2 or 3, such that the sum of p and q is from 1 to 4; and
each occurrence of t is independently 0 or 1.
2. The compound of claim 1 , wherein Q is phenylene or pyridylene.
3. The compound of claim 2 , wherein Q is:
4. The compound of claim 1 , wherein Y is —NH— or —O—.
5. The compound of claim 1 , wherein Z is —O—.
6. The compound of claim 4 , wherein Z is —O—.
7. The compound of claim 1 , wherein W is —C(O)O— or —S(O) 2 —.
8. The compound of claim 1 , wherein p is 1 and q is 2.
9. The compound of claim 1 , wherein R 1 is cyclopropyl or cyclobutyl.
10. The compound of claim 1 , wherein R 2 is H, methyl or methoxy.
11. The compound of claim 1 , wherein R 3 is alkyl or cycloalkyl.
12. The compound of claim 11 , wherein R 3 is isopropyl, t-butyl or cyclopropyl.
13. The compound of claim 1 , wherein J and L are each —N— and K is —CH—.
14. The compound of claim 1 , wherein each occurrence of R 8 is H.
15. The compound of claim 1 having the formula:
wherein:
G is —CH— or —N—;
W is —C(O)O— or —S(O) 2 —;
Y is —O— or —N(R 5 )—;
R 1 is cycloalkyl;
R 2 is H, alkyl or —O-alkyl;
R 3 is alkyl or cycloalkyl;
R 4 represents 1 to 4 optional substituents, which can be the same or different, and which are selected from alkyl, halo, —CN and —O-alkyl; and
each occurrence of R 5 is independently H or alkyl.
16. The compound of claim 1 having the formula:
wherein:
G is —CH— or —N—;
Y is —O— or —NH—;
R 1 is cyclopropyl or cyclobutyl;
R 2 is H, methyl or methoxy;
R 3 is alkyl; and
R 4 is H, Cl or F.
17. The compound of claim 1 having the formula:
wherein:
G is —CH— or —N—;
Y is —O— or —NH—;
R 1 is cyclopropyl or cyclobutyl;
R 2 is H, methyl or methoxy;
R 3 is cycloalkyl; and
R 4 is H, Cl or F.
18. A compound having the structure:
or a pharmaceutically acceptable salt or stereoisomer thereof.
19. A composition comprising an effective amount of one or more compounds of claim 1 or a pharmaceutically acceptable salt or stereoisomer thereof, and at least one pharmaceutically acceptable carrier.