Indazole and azaindazole substituted compounds as mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction

A compound having a structure represented by the formula:

• wherein the variables are substituted or unsubstituted and:
• X is N, alkyl, alkoxy, or CH, CD, and optionally together with Y forms a six membered ring optionally substituted with one or more R;
• Y is N, alkyl, alkoxy, or CH and optionally together with X forms a six membered ring optionally substituted with one or more R;
• Z is N, CH, CD, or C-halogen, C—Me, C—O—Me, C—CN;
• R is independently chosen from H, Cl, F, CN, alkyl, cycloalkyl, Me, OMe, alkoxy;
• X1 is N, NH, CH, CD, CR1;
• X2 is N, NR1, or NR2;
• X3 is N, NH, CH, CD, CR1;
• provided that one of X1 or X3 is CH or CR1;
• R1 is independently H, alkyl, cycloalkyl, phenyl, cycloheteroalkyl, halogen, CF3, Cl, CD3, CD2R, CDRR2, aryl, heteroaryl, SO2R3. O—R, O-aryl, O-heteroaryl, NHR, NR2R2, perfluorinated alkyl, heteroalkyl, benzyl, heteroaryl benzyl (CH2heteroaryl), alkene, alkyl-cycloalkyl, O-alkyl-cycloalkyl, CH2-cycloalkyl, CH2—CF3, hydroxyalkyl, alkyl-alkoxy, alkyl-cycloheteroalkyl, alkyl-heteroaryl, alkyl-carboxylic acid, CO—CF3, alkyl-CO—O-alkyl, CO-alkyl-sulfonyl-alkyl, CO-cycloheteroalkyl, CO—NH-cycloalkyl, CN, alkoxy-cycloalkyl, alkoxy-cycloheteroalkyl, O-alkoxy, O-phenyl, O-alkoxyphenyl-O-dioxothian, hydroxyl, alkoxy, O-alkyl-heteroaryl, O-alkyl-cycloheteroalkyl, alkoxy-heteroalkyl, methylsulfonyl, O-cycloheteroalkyl, O-alkoxy-cycloheteroalkyl, O-alkoxyaryl, alkoxy-heteroaryl, alkoxy, alkyl-phenyl, cycloheteroalkyl, O—CD3, O—CD2R, hydroxyl, amino, CO-alkyl, CO-cycloalkyl, CO-alkyl-cycloalkyl, CO-amino-alkyl-sulfonylmethyl, CO-amino-cycloalkyl;
• R2 is independently H, heteroaryl, alkyl, phenyl, aryl, O-cycloheteroalkyl, alkoxy-cycloheteroalkyl, O-alkoxy-cycloheteroalkyl, O-alkoxyaryl, O-heteroaryl, alkoxy-heteroaryl, alkoxy, alkoxycycloheteroalkyl, alkyl-phenyl, cycloheteroalkyl, O—CD3, O—CD2R, hydroxyl, amino, cycloalkyl, CH2-cycloalkyl, CO-alkyl;
• cycloheteroalkyl, H, CF3, halogen, CD3, CD2R, CDRR2, aryl, SO2R3, OR, Oaryl, NHR, NR1R1, perfluorinated alkyl, heteroalkyl, benzyl, heteroaryl benzyl (CH2heteroaryl), alkene, alkyl-cycloalkyl, CH2-cycloalkyl, CH2—CF3, hydroxyalkyl, alkyl-alkoxy, alkyl-cycloheteroalkyl, alkyl-heteroaryl, O-alkyl-heteroaryl, alkyl-carboxylic acid, CO—CF3, alkyl-CO—O-alkyl, CO-alkyl-sulfonyl-alkyl, CO-cycloheteroalkyl, CO—NH-cycloalkyl, CN, alkoxy-cycloalkyl, O-dioxothian, hydroxyl, methylsulfonyl;
• R3 is H, alkyl, alkoxyphenyl, pyridine, nitrilepyridine, chloropyridine;
• or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable derivative thereof.