Aryl and heteroaryl sulfones as mGluR4 allosteric potentiators, compositions, and methods of treating neurological dysfunction
In one aspect, the invention relates to sulfone compounds which are useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds, for example, in treating neurological and psychiatric disorders or other disease state associated with glutamate dysfunction.
1. A compound of a structure represented by the following formula:
wherein:
X 1 is S or SO 2 ;
R 1 is pyridine optionally substituted with one or more R 8 ;
R 4 is phenyl optionally substituted with one or more R 8 ;
R 5 and R 6 are H;
R 7 is selected from: H, halogen, C 1-6 alkyl, C 3-10 cycloalkyl, OC 1-6 alkyl, aryl, heteroaryl, CN or CF 3 ;
R 8 is selected from: H, OH, halogen, C 1-6 alkyl, C 3-10 cycloalkyl, CN, OC 1-6 alkyl or CF 3 ;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein the compound is selected from the following formula:
3. The compound of claim 1 , wherein R 1 is 2-pyridine optionally substituted with one or more R 8 .
4. The compound of claim 1 , wherein R 4 is phenyl optionally substituted with at least one halogen.
5. The compound of claim 1 , wherein R 7 is halogen.
6. The compound of claim 1 , wherein R 1 is halogen-substituted and/or alkyl-substituted.
7. The compound of claim 1 , of the following formula:
or a pharmaceutically acceptable salt thereof.
8. A pharmaceutical composition comprising a compound of the following formula:
wherein:
X 1 is S or SO 2 ;
R 1 is pyridine optionally substituted with one or more R 8 ;
R 4 is phenyl optionally substituted with one or more R 8 ;
R 5 and R 6 are H;
R 7 is selected from: H, halogen, C 1-6 alkyl, C 3-10 cycloalkyl, OC 1-6 alkyl, aryl, heteroaryl, CN or CF 3 ;
R 8 is selected from: H, OH, halogen, C 1-6 alkyl, C 3-10 cycloalkyl, CN, OC 1-6 alkyl or CF 3 ;
or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.
9. The pharmaceutical composition of claim 8 , wherein the compound is selected from the following formula:
10. The pharmaceutical composition of claim 7 , wherein R 1 is 2-pyridine optionally substituted with one or more R 8 .
11. The pharmaceutical composition of claim 8 , wherein R 4 is phenyl optionally substituted with at least one halogen.
12. The pharmaceutical composition of claim 8 , wherein R 7 is halogen.
13. The pharmaceutical composition of claim 8 , wherein R 1 is halogen-substituted and/or alkyl-substituted.
14. The pharmaceutical composition of claim 8 , wherein the compound is selected from the following formula:
or a pharmaceutically acceptable salt thereof.
15. A compound of the following formula:
or a pharmaceutically acceptable salt thereof.
16. A pharmaceutical composition comprising a compound of the following formula:
or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.