Pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]-pyrimidine adenosine A2a receptor antagonists

A compound having the structural formula

• or a pharmaceutically acceptable salt thereof, wherein
• R is R6-phenyl, R6-furanyl, R6-thienyl, R6-pyridyl, R6-pyridyl N-oxide, R6-oxazolyl, R6-pyrrolyl or cycloalkenyl;
• R1, R2, R3, R4 and R5 are independently selected from the group consisting of H, alkyl and alkoxyalkyl;
• R6 is 1 to 3 substituents independently selected from the group consisting of H, alkyl, —CF3, halogen, —NO2, —CN, —NR7R8, alkoxy, alkylthio, alkylsulfinyl and alkylsulfonyl;
• R7 is H or alkyl;
• R8 is H, alkyl, alkylC(O)— or alkyl-SO2—;
• Z is R9,R10-aryl or R9,R10-heteroaryl;
• R9 is alkenyl, hydroxyalkyl, alkoxyalkyl, alkoxy-alkoxy-alkyl-, (di-alkoxy)-alkyl, (hydroxy)-alkoxyalkyl, R15-cycloalkyl, R15-cycloalkylalkyl, cycloalkyl-oxy, cycloalkyl-O-alkoxy, cyanoalkyl, —C(O)R13, —N(R11)(R12), N(R11)(R12)-alkyl-, —C(O)N(R13)(R16), -alkylene-C(O)—N(R11)2, —C(O)—(R15-heterocycloalkyl), R15-heterocycloalkyl-alkyl, R15-heterocycloalkyl-alkoxy, R19-heteroaryl, CF3-alkylene-O-alkyl, CF3-hydroxyalkyl, (CF3)(hydroxy)alkoxy, cyano-alkoxy, -alkylene-C(O)—O-alkyl, —SO2-N (alkyl)2, (cycloalkyl)hydroxyalkyl, (hydroxyalkyl)alkoxy, (dihydroxy)alkyl, (dihydroxy)alkoxy or —C(═NOR17)—CF3;
• R10 is 1 to 3 substituents independently selected from the group consisting of hydrogen, alkyl, alkenyl, hydroxy, alkoxy, hydroxyalkyl, hydroxy-alkoxy, alkoxyalkyl, alkoxyalkoxy, alkoxy-alkoxy-alkyl-, (di-alkoxy)-alkyl, (hydroxy)-alkoxyalkyl, R15-cycloxyayl, R15-cycloalkylalkyl, cycloalkyl-oxy, cycloalkyl-O-alkoxy, alkyl-SO2—, alkyl-SO—, halo, —CN, cyanoalkyl, —CHF2, —CF3, —OCHF2, —OCF3, —C(O)R13, —O-alkylene-C(O)OR13, —C(O)O-alkyl, —N(R11)(R12), N(R11)(R12)-alkyl, N(R11)(R12)-alkoxy, —C(O)N(R13)(R16), R19-heteroaryl, R15-heterocycloalkyl, R15-heterocycloalkyl-alkyl, R15-heterocycloalkyl-alkoxy, R15-heterocycloalkyl-oxy, CF3-alkylene-O-alkyl, CF3-hydroxyalkyl, (CF3)(hydroxy)alkoxy, cyano-alkoxy, -alkylene-C(O)—O-alkyl, —SO2-N(alkyl)2, (cycloalkyl)hydroxyalkyl, (hydroxyalkyl)alkoxy, (dihydroxy)alkyl, (dihydroxy)alkoxy, —C(═NOR17)-alkyl and —C(═NOR17)—CF3;
• or an R9 group and an R10 group on adjacent carbon ring atoms together form —O—(CH2)2—O—, —CH2—O—(CH2)2—O—, —O—(CH2)2—, —(CH2)3—O—, —O—(CH2)3—O—, —(CH2)3— or —CH2—CH═CH—, wherein the ring formed by the R9 and R10 substituents and the ring carbon atoms to which they are attached is substituted by R16;
• or an R9 group and an R10 group on adjacent carbon ring atoms together form —N(R11)—C(O)—O—, —N(R11)—C(O)—S— or —N(R12)—(CH2)2—;
• or an R9 group and an R10 group on adjacent carbon ring atoms together form —(CH2)2CH(OR18)—, —CH2CH(OR18)CH2—, —(CH2)3CH(OR18)—, —(CH2)2CH(OR18)CH2—, —(CH2)2C(O)—, —CH2C(O)CH2—, —(CH2)3C(O)—, —(CH2)2C(O)CH2—, —O(CH2)2CH(OR18)— or —OCH2CH(OR18)CH2—, wherein the ring formed by the R9 and R10 substituents and the ring carbon atoms to which they are attached is optionally substituted on a carbon atom by hydroxyalkyl or alkoxyalkyl;
• each R11 is independently selected from the group consisting of H and alkyl;
• each R12 is independently selected from the group consisting of H, alkyl, cycloalkyl, hydroxyalkyl, alkoxyalkyl, —C(O)-alkyl, —C(O)O-alkyl, (alkoxy)hydroxyalkyl, alkoxyalkyl-C(O)—, —SO2alkyl, -alkylene-C(O)alkyl and -alkylene-C(O)O-alkyl;
• R13 is H, alkyl or —CF3;
• R15 is 1 to 3 substituents independently selected from the group consisting of H, alkyl, —OH, alkoxy, alkoxyalkyl and hydroxyalkyl;
• or two R15 substituents, taken together with the carbon to which they are both attached, form a —C(═O)— group;
• R16 is H, alkyl, alkoxyalkyl, OH or hydroxyalkyl;
• R17 is H or alkyl;
• R18 is H or alkyl;
• and
• R19 is 1 or 2 substituents independently selected from the group consisting of H, alkyl, hydroxyalkyl, alkoxyalkyl, —C(O)N(R11)(R12) and —N(R11)2.