Isoquiniline and napthalene-substituted compounds as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction

A compound having a structure of the following formula:

• wherein the variables are substituted or unsubstituted, and:
• X1 is CH, CD, C—R2, N, or is N and together with R1 forms a 5 or 6 membered ring;
• X2 is CH, CD, C—R2, or N;
• Y is N, CH, CD, C-alkyl, or may form a 6-membered ring with Y optionally substituted with at least one R;
• R is halogen, CN, Me, alkyl, OMe, alkoxy;
• R1 is H, alkyl, aklene, cycloalkyl, NR4R5, aryl, halogen, CF3, cycloheteroalkyl, alkoxy, OH, CN, Oalkyl, Oaryl, Oheteroaryl, NHalkyl, NHaryl, NHheteroaryl, heteroaryl, CH2F, CHF2, NR4R5, CO-heteroaryl, CO—NH-alkyl, CO—NH-methoxyalkyl, CO-amino, CO-aryl, CO-heteroaryl, CO-aminocycloalkyl, CO-amino-alkoxy, CO-alkyl, Nalkylalkyl, NH-alkoxy, or together with X1 forms a 5 or 6 membered ring;
• R2 is H, halogen, alkyl, alkoxy, OMe;
• R3 is H, alkyl, cycloalkyl, aryl, heteroaryl;
• R4 is H, alkyl, cycloalkyl, aryl, heteroaryl, alkyl-aryl, methoxyalkyl;
• R5 is H, alkyl, cycloalkyl, aryl, heteroaryl;
• or a pharmaceutically acceptable salt thereof.

A compound of the following formula:

• wherein the variables are substituted or unsubstituted, and:
• R is substituted or unsubstituted, and chosen from halogen, CN, Me, alkyl, OMe, alkoxy;
• R2 is substituted or unsubstituted, and chosen from R2 is H, halogen, alkyl, alkoxy, OMe, CONH2, CN, O;
• R3 is substituted or unsubstituted, and chosen from H, alkyl, alkene, cycloalkyl, aryl, heteroaryl, alkoxy, hydroxyl, amino, aminoalkoxy, halogen, or together with X2 forms a 5 or 6 membered ring containing C or N as the ring members;
• or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable derivative thereof.

A pharmaceutical composition comprising a compound having a structure represented by a formula:

• wherein the variables are substituted or unsubstituted, and:
• R is halogen, CN, Me, alkyl, OMe, alkoxy;
• R1 is H, alkyl, aklene, cycloalkyl, NR4R5, aryl, halogen, CF3, cycloheteroalkyl, alkoxy, OH, CN, Oalkyl, Oaryl, Oheteroaryl, NHalkyl, NHaryl, NHheteroaryl, heteroaryl, CH2F, CHF2, NR4R5, CO-heteroaryl, CO—NH-alkyl, CO—NH-methoxyalkyl, CO-amino, CO-aryl, CO-heteroaryl, CO-aminocycloalkyl, CO-amino-alkoxy, CO-alkyl, Nalkylalkyl, NH-alkoxy, or together with X1 forms a 5 or 6 membered ring;
• R2 is H, halogen, alkyl, alkoxy, OMe, CONH2, CN, O;
• R3 is H, alkyl, alkene, cycloalkyl, aryl, heteroaryl, alkoxy, hydroxyl, amino, aminoalkoxy, halogen, or together with X2 forms a 5 or 6 membered ring;
• R4 is H, alkyl, cycloalkyl, aryl, heteroaryl, alkyl-aryl, methoxyalkyl;
• R5 is H, alkyl, cycloalkyl, aryl, heteroaryl;
• or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable carrier.