US 7,368,449 B2
2-alkynyl- and 2-alkenyl-pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]-pyrimidine adenosine A2a receptor antagonists
Bernard R. Neustadt, West Orange, N.J. (US); Jinsong Hao, Belle Mead, N.J. (US); Hong Liu, River Edge, N.J. (US); Craig D. Boyle, Branchburg, N.J. (US); Samuel Chackalamannil, Califon, N.J. (US); Unmesh G. Shah, Scotch Plains, N.J. (US); and Andrew Stamford, Chatham Township, N.J. (US)
Assigned to Schering Corporation, Kenilworth, N.J. (US)
Filed on May 23, 2005, as Appl. No. 11/135,261.
Application 11/135261 is a continuation of application No. 10/829416, filed on Apr. 21, 2004, granted, now 6,897,217.
Claims priority of provisional application 60/464840, filed on Apr. 23, 2003.
Prior Publication US 2005/0222164 A1, Oct. 06, 2005
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/497 (2006.01)
U.S. Cl. 514—252.16  [514/267; 544/251] 16 Claims
 
1. A method of treating Extra Pyramidal Syndrome, dystonia, restless leg syndrome or periodic limb movement in sleep comprising administering to a mammal in need of such treatment an effective amount of a compound having the structural formula

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof, wherein
R is

OG Complex Work Unit Drawing
R1, R2, R3, R4 and R5 are independently selected from the group consisting of H, alkyl and alkoxyalkyl;
R6 is H, alkyl, hydroxyalkyl or —CH2F;
R7, R8 and R9 are independently selected from the group consisting of H, alkyl, alkoxy, alkylthio, alkoxyalkyl, halo and —CF3;
Z is R10-aryl, R10-heteroaryl or

OG Complex Work Unit Drawing
R10 is 1 to 5 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-cycloalkyl, 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), R11-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 two R10 groups on adjacent carbon ring atoms together form —O—CH2—O—, —O—(CH2)2—O—, —CH2—O—(CH2)2—O—, —O—(CH2)2—, —(CH2)3—O—, —O—(CH2)3—O—, —(CH2)3—, wherein the ring formed by the two R10 substituents and the ring carbon atoms to which they are attached is substituted by R16;
or two R10 groups on adjacent carbon ring atoms together form —N(R11)—C(O)—O—, —N(R11)—C(O)—S—, —(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 two 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, 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;
R14 is H, alkyl, alkoxyalkyl, alkyl-C(O)— or alkoxy-C(O)—;
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; and
R18 is H or alkyl.