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

A method for the treatment of a neurotransmission dysfunction and other disease states associated with mGluR4 activity in a mammal comprising the step of administering to the mammal at least one compound in a dosage and amount effective to treat the dysfunction in the mammal, the compound having a structure represented by a formula:

• X is CH, C-alkyl, N, NH, N-alkyl, alkoxy, or may form a 6-membered ring with Y optionally substituted with at least one R;
• Y is CH, C-alkyl, N, or may form a 6-membered ring with X optionally substituted with at least one R;
• Z is independently N, CH, C-alkyl, C-halogen, C-Me, C—Oalkyl, C—OMe
• X1 is O or C—R1;
• X2 is O or C—R2;
• R is independently H, halogen, CN, Me, alkyl, alkoxy, OMe, aryl, heteroaryl, alkyl-aryl, alkyl-heteroaryl, cycloalkyl, alkyl-cycloalkyl;
• R1 is independently H, alkoxy, amino, alkyl-alkoxy, alkyl, CN, cycloalkyl, alkyl-cycloalkyl, cycloheteroalkyl, alkyl-cycloheteroalkyl, CF3, halogen, CD3, CD2R, CDRR2, CONR3R4, aryl, heteroaryl, alkyl-aryl, alkyl-heteroaryl, SO2R2, OR, OR2, Oaryl, Oheteroaryl, NHR, NR3R4, fluorinated alkyl, difluorinated alkyl, trifluorinated alkyl, heteroalkyl, benzyl, heteroaryl benzyl (CH2heteroaryl), propanamide, diethylpropanamide, CH2CONR3R4;
• CH2NHR;
• CH2NHR3R4;
• R2 is independently H, alkoxy, amino, alkyl-alkoxy, alkyl, CN, cycloalkyl, alkyl-cycloalkyl, cycloheteroalkyl, alkyl-cycloheteroalkyl, CF3, halogen, CD3, CD2R, CDRR1, CONR3R4, aryl, heteroaryl, alkyl-aryl, alkyl-heteroaryl, SO2R1, OR, OR1, Oaryl, Oheteroaryl, NHR, NR3R4, fluorinated alkyl, difluorinated alkyl, trifluorinated alkyl, heteroalkyl, benzyl, heteroaryl benzyl (CH2heteroaryl), propanamide, diethylpropanamide, CH2CONR3R4;
• CH2NHR;
• CH2NHR3R4;
• R3 is H, alkoxy, amino, alkyl-alkoxy, alkyl, CN, cycloalkyl, alkyl-cycloalkyl, cycloheteroalkyl, alkyl-cycloheteroalkyl, CF3, halogen, CD3, CD2R, CDRR2, aryl, heteroaryl, alkyl-aryl, alkyl-heteroaryl, SO2R2, OR, OR2, Oaryl, Oheteroaryl, NHR, fluorinated alkyl, difluorinated alkyl, trifluorinated alkyl, heteroalkyl, benzyl, heteroaryl benzyl (CH2heteroaryl), propanamide, diethylpropanamide, CH2NHR;
• R4 is H, alkoxy, amino, alkyl-alkoxy, alkyl, CN, cycloalkyl, alkyl-cycloalkyl, cycloheteroalkyl, alkyl-cycloheteroalkyl, CF3, halogen, CD3, CD2R, CDRR2, aryl, heteroaryl, alkyl-aryl, alkyl-heteroaryl, SO2R2, OR, OR2, Oaryl, Oheteroaryl, NHR, fluorinated alkyl, difluorinated alkyl, trifluorinated alkyl, heteroalkyl, benzyl, heteroaryl benzyl (CH2heteroaryl), propanamide, diethylpropanamide, CH2NHR;
• or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable derivative thereof.