Triazole compounds and their use as metabotropic glutamate receptor antagonists

A compound according to Formula II,

• wherein,
• P is aryl;
• if m=1 then R1 is attached to P at the meta position of the ring P relative to the attachment point of P to the 5-membered ring, and if m=2 then R1 is attached to P at the 2-, and 5-positions of the ring P to the 5-membered ring;
• R1 is selected from the group consisting of hydroxy, halo, nitro, C1-6alkylhalo, OC1-6alkylhalo, C1-6alkyl, OC1-6alkyl, C2-6alkenyl, OC2-6alkenyl, C2-6alkynyl, OC2-6alkynyl, C0-6alkylC3-6cycloalkyl, OC0-6alkylC3-6cycloalkyl, C0-6alkylaryl, OC0-6alkylaryl, CHO, (CO)R5, O(CO)R5, O(CO)OR5, O(CN)OR5, C1-6alkylOR5, OC2-6alkylOR5, C1-6alkyl(CO)R5, OC1-6alkyl(CO)R1, C0-6alkylCO2R5, OC1-6alkylCO2R5, C0-6alkylcyano, OC2-6alkylcyano, C0-6alkylNR5R6, OC2-6alkylNR5R6, C1-6alkyl(CO)NR5R6, OC1-6alkyl(CO)NR5R6, CO0-6alkylNR5(CO)R6, OC2-6alkylNR5(CO)R6, C0-6alkylNR5(CO)NR5R6, C0-6alkylSR5, OC2-6alkylSR5, C0-6alkyl(SO)R5, OC2-6alkyl(SO)R5, C0-6alkylSO2R5, OC2-6alkylSO2R5, C0-6alkyl(SO2)NR5R6, OC2-6alkyl(SO2)NR5R6, C0-6alkylNR5(SO2)R6, OC2-6alkylNR5(SO2)R6, C0-6alkylNR5(SO2)NR5R6, OC2-6alkyNR5(SO2)NR5R6, (CO)NR5R6, O(CO)NR5R6, NR5OR6, C0-6alkylNR5(CO)OR6, OC2-6alkylNR5(CO)OR6, SO3R5 and a 5- or 6-membered ring containing atoms independently selected from the group consisting of C, N, O and S;
• R5 and R6 are independently selected from a group consisting of hydrogen, C1-6alkyl, C3-7cycloalkyl and aryl;
• X1 and X2 are independently selected from the group consisting of CR4, and N;
• X3 is selected from the group consisting of CR4, N, and O;
• wherein at least one of X1 X2 and X3 is not N;
• R4 is selected from the group consisting of H, ═O, C1-6alkyl, OH;
• R3 is selected from the group consisting of H, C1-6alkyl, hydroxy, C0-6alkylcyano, oxo, ═NR5, ═NOR5, C1-4alkylhalo, halo, C3-7cycloalkyl, O(CO)C1-4alkyl, C1-4alkyl(SO)C0-4alkyl, C1-4alkyl(SO2)C0-4alkyl, (SO)C0-4alkyl, (SO2)C0-4alkyl, OC1-4alkyl, C1-4alkylOR5 and C0-4alkylNR5R6;
• X4 is selected from the group consisting of CR7R8, NR7, O, S, SO, and SO2;
• R7 and R8 are independently selected from a group consisting of hydrogen, C1-6alkyl, C3-7cycloalkyl and aryl;
• X5 and X6 are independently selected from the group consisting of C, N, O and S;
• R2 is selected from the group consisting of hydroxy, C0-6alkylcyano, ═NR5, ═NOR5, C1-4alkylhalo, halo, C1-6alkyl, C3-6cycloalkyl, C0-6alkylaryl, C0-6alkylheteroaryl, C0-6alkylcycloalkyl, C0-6alkylheterocycloalkyl, OC1-4alkyl, OC0-6alkylaryl, O(CO)C1-4alkyl, (CO)OC1-4alkyl, C0-4alkyl(S)C0-4alkyl, C1-4alkyl(SO)C0-4alkyl, C1-4alkyl(SO2)C0-4alkyl, (SO)C0-4alkyl, (SO2)C0-4alkyl, C1-4alkylOR5, C0-4alkylNR5R6 and a 5- or 6-membered ring containing atoms independently selected from C, N, O and S, and wherein said ring may be substituted by one or more A;
• and
• any C1-6alkyl, aryl or heteroaryl defined under R1, R2 and R3 may be substituted by one or more A;
• A is selected from the group consisting of hydrogen, hydroxy, halo, nitro, oxo, C0-6alkylcyano, C0-4alkylC3-6cycloalkyl, C1-6alkyl, C1-6alkylhalo, OC1-6alkylhalo, C2-6alkenyl, C0-3alkylaryl, C0-6alkylOR5, OC2-6alkylOR5, C1-6alkylSR5, OC2-6alkylSR5, (CO)R5, O(CO)R5, OC2-6alkylcyano, OC1-6alkylCO2R5, O(CO)OR5, OC1-6alkyl(CO)R5, C1-6alkyl(CO)R5, NR5OR6, C1-6alkylNR5R6, OC2-6alkylNR5R6, C0-6alkyl(CO)NR5R6, OC1-6alkyl(CO)NR5R6, OC2-6alkylNR5(CO)R6, C0-6alkylNR5(CO)R6, C0-6alkylNR5(CO)NR5R6, O(CO)NR5R6, C0-6alkyl(SO2)NR5R6, OC2-6alkyl(SO2)NR5R6, C0-6alkylNR5(SO2)R6, OC2-6alkylNR5(SO2)R6, SO3R5, C1-6alkylNR5(SO2)NR5R6, OC2-6alkyl(SO2)R5, C0-6alkyl(SO2)R5, C0-6alkyl(SO)R5, OC2-6alkyl(SO)R5 and a 5- or 6-membered ring containing one or more atoms independently selected from the group consisting of C, N, O and S;
• m is selected from 1 and 2;
• n is selected from 0, 1, 2, 3 and 4;
• p is selected from 1 and 2;
• and
• and a salts or hydrates thereof,