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 diabetic complication, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of a G protein-coupled receptor (GPCR) in a patient. The compounds are of structure (I).
1. A compound having the formula:
or a pharmaceutically acceptable salt thereof,
wherein:
A is —O— or —N(R 12 )—;
W is —C(O)O—, —C(O)— or —S(O) 2 —;
—X—Y is CH 2 —CH 2 or CH═CH;
R 3 is alkyl, haloalkyl or cycloalkyl, wherein the cycloalkyl group can be optionally substituted with up to 4 substituents each independently selected from the group consisting of: alkyl and halo;
each occurrence of R 7 is independently H or alkyl;
R 8 is aryl or heteroaryl, optionally substituted with R 9 ;
R 9 represents from 1-4 optional substituents, which can be the same or different, selected from alkyl, alkenyl, alkynyl, halo, haloalkyl, —CN, —NO 2 , —O-(alkylene) t -R 13 , —S-(alkylene) t -R 13 , —N(R 13 )-(alkylene) t -R 13 , -(alkylene) t -R 13 , —C(O)-(alkylene) t -R 13 , —C(O)O-(alkylene) t -R 13 , —N(R 7 )C(O)-(alkylene) t -R 13 , —C(O)N(R 7 )-(alkylene) t -R 13 , —OC(O)-(alkylene) t -R 13 , —N(R 7 )C(O)N(R 7 )-(alkylene) t -R 13 , —N(R 7 )C(O)O-(alkylene) t -R 13 , —S(O)-(alkylene) t -R 13 or —S(O) 2 (alkylene) t -R 13 ;
R 12 is H, alkyl or aryl;
each occurrence of R 13 is independently H, haloalkyl, aryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl or heteroaryl; and
each occurrence of t is independently 0 or 1.
2. The compound of claim 1 having the structure:
or a pharmaceutically acceptable salt thereof.
3. A composition comprising one or more compounds of claim 1 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.
4. A method for treating type II diabetes in a patient, the method comprising administering to the patient an effective amount of one or more compounds of claim 1 , or a pharmaceutically acceptable salt thereof.
5. The compound of claim 1 where A is —NH—.
6. The compound of claim 1 where A is —O—.
7. The compound of claim 5 where W is —C(O)O—.
8. The compound of claim 5 where W is —S(O) 2 —.
9. The compound of claim 1 where R 8 is phenyl, optionally substituted with R 9 .
10. The compound of claim 1 where R 8 is pyridyl, optionally substituted with R 9 .
11. The compound of claim 9 where R 3 is cyclopropyl or cyclobutyl, optionally substituted with up to 4 substituents each independently selected from the group consisting of: alkyl and halo.
12. The compound of claim 9 where R 3 is isopropyl or t-butyl.
13. The compound of claim 1 where R 9 is independently selected from alkyl, halo, —CN, cycloalkyl, alkynyl, heteroaryl, —S(O) 2 -alkyl, or S(O) 2 -cycloalkyl.
14. The compound of claim 1 where R 9 is independently selected from methyl, F, Cl, —CN, , or —S(O) 2 CH 3 .
15. The compound of claim 1 where R 8 is phenyl, substituted with 1 or 2 groups, each independently selected from halo, —CN or —S(O) 2 -alkyl.
16. The compound of claim 1 where R 8 is heteroaryl, which is substituted with 1 or 2 groups, each independently selected from alkyl or heteroayl.