[1,2,4]-Triazole bicyclic adenosine A2a receptor antagonists

A compound represented by the structural formula

• 186
• or a pharmaceutically acceptable salt thereof, wherein:
• A is C(R1) or N;
• R1 and R1a are independently selected from the group consisting of H, (C1-C6)-alkyl, halo, CN and —CF3;
• Y is —O—, —S—, —SO—, —SO—, R5-heteroaryldiyl, R5-arylene or
• 187
• p and q are independently 2-3;
• Q and Q1 are independently selected from the group consisting of
• 188
• provided that at least one of Q and Q1 is
• 189
• R is R5-aryl, R5-heteroaryl, R6—(C2-C6)alkenyl or R6—(C2-C6)alkynyl;
• R2 is R5-aryl, R5-heteroaryl, R5-aryl(C1-C6)alkyl or R5-heteroaryl(C1-C6)alkyl;
• or R2—Y is
• 190
• U, V, and W are independently selected from the group consisting of N and CR1, provided that at least one of U, V and W is CR1;
• n is 1, 2or3;
• and
• (a) A is C(R1) and X is —C(R3)(R3a)—, —C(O)—, —O—, —S—, —O—, —SO2—, R4-arylene, R4-heteroaryldiyl, or —N(R9)—;
• or A is C(R1), Y is a bond, and X is —C(R3)(R3a)—, —C(O)—, —O—, —S—, —SO—, —SO2—, R4-arylene, —N(R9)— or R4-heteroaryldiyl, provided that when X is —N(R9)— or R4-heteroaryldiyl, R2 is not phenyl or phenyl-(C1-C6)alkyl;
• or
• (b) A is N, X is —N(R9)—, Y is R5-arylene and R2 is
• 191
• or n is 2 or 3;
• and
• (c) A is N and X is —C(R3)(R3a)—, —C(O)—, —O—, —S—, —SO—, —SO2—, —N(R9)—, R4-arylene or R4-heteroaryldiyl;
• or A is N, Y is a bond and X is —C(O)—, —N(R9)—, R4-arylene or R4-heteroaryldiyl;
• or A is N, Y is —N(R9a)—, —C(O)N(R9a)— or —O—(CH2)2—N(R9a)—, and X is —N(R9)—;
• or A is N, X is —N(R9)—, and Y and R2 together are
• 192
• or n is 0;
• and
• (d) A is N, Y is a bond, X is —N(R9)—, and R2 is
• 193
• (e) A is N, X is —N(R9)— and Y and R2 together are
• 194
• wherein
• Z is —C(O)—CH2—, —C(O)—CH(C1-C6 alkyl)-, —CH2—CH(C1-C6 alkyl)-, or —CH(C1-C6 alkyl)-CH2—;
• R3and R3a are independently selected from the group consisting of H, —OH, C1-C6 alkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, amino(C1-C6)alkyl, (C1-C6)alkylamino(C1-C6)alkyl and di(C1-C6)alkylamino(C1-C6)alkyl;
• R4 is 1-3 substituents selected from the group consisting of H, (C1-C6)alkyl, —OH, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkoxy, halo, —CF3, and —CN;
• R5 is 1-3 substituents independently selected from the group consisting of H, (C1-C6)alkyl, —OH, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)-alkoxy, halo, —CF3, —CN, —NH2, (C1-C6)alkylamino, di(C1-C6)alkylamino, amino(C1-C6)-alkyl, (C1-C6)alkylamino(C1-C6)alkyl, di(C1-C6)alkylamino(C1-C6)alkyl, (C1-C6)alkanoyl- amino, (C1-C6)alkanesulfonylamino, (C1-C6)alkylthio, (C1-C6)alkylthio(C1-C6)alkyl, R6—(C2-C6)alkenyl, R6—(C2-C6)alkynyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy-C(O)-amino, or heterocycloalkyl(C1-C6)alkyl;
• R6 is 1 to 3 substituents independently selected from the group consisting of H, (C1-C6)alkyl, —OH, (C1-C6)alkoxy and halo;
• R7 and R7a are independently selected from the group consisting of H, (C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, R8-aryl and R8-heteroaryl, or an R7 and an R7a substituent on the same carbon can form ═O;
• R8 is 1 to 3 substituents independently selected from H, (C1-C6)alkyl, —OH, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkoxy, halo, —CF3, and —CN;
• R9 and R9a are independently selected from the group consisting of H, (C1-C6)alkyl, hydroxy(C2-C6)alkyl, (C1-C6)alkoxy(C2-C6)alkyl, amino(C2-C6)alkyl, (C1-C6)alkylamino(C2-C6)alkyl, di(C1-C6)alkylamino(C2-C6)alkyl, halo-(C3-C6)-alkenyl, CF3—(C1-C6)alkyl, (C3-C6)alkenyl, —(C3-C6)cycloalkyl and (C3-C6)cycloalkyl-(C1-C6)alkyl;
• and
• R10 is H, —C(O)—O—(C1-C6)alkyl, R5-aryl, —C(O)—(C1-C6)alkyl, —C(O)—(R5-aryl) or R5-aryl-(C1-C6)alkyl.