Selective antagonists of a2a adenosine receptors

Abstract

The present invention provides compounds of formulae Ia and Ib: wherein R 1-5 , Q, X, Y, Z, p, q, and r are as defined herein. The compounds are potent and selective antagonists of A 2A adenosine receptors (ARs). The invention further includes pharmaceutical compositions containing these compounds and methods of using the same.

1 . A compound of formula Ia or Ib or stereoisomer or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein: 
         the (CH 2 ) portions of (CH 2 ) n  and (CH 2 ) q  are independently substituted with 0-2 groups selected from OH, ═O, C 1-4  alkyl, C 3-6  cycloalkyl, and benzyl; 
         Q is O or S; 
         X is CH or N; 
         Y is selected from the group consisting of O, NY 1 , OCH 2 CH 2 OCH 2 , OCH 2 CH 2 OCH 2 CH 2 OCH 2 , OCH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 OCH 2 , NY 1 CH 2 CH 2 OCH 2 , NY 1 CH 2 CH 2 OCH 2 CH 2 OCH 2 , and NY 1 CH 2 CH 2 OCH 2 CH 2 OCH 2 CH 2 OCH 2 ; 
         alternatively, Y is absent; 
         Y 1  is selected from the group consisting of H, C 1-4  alkyl, benzyl, C 3-6  cycloalkyl, and (C 3-6  cycloalkyl)C 1-4  alkylene; 
         Z is selected from the group consisting of aryl and heteroaryl, wherein Z is attached via a carbon atom and is substituted with 1-4Z 1  groups; 
         Z 1  is independently selected from the group consisting of F, Cl, Br, I, C 1 - 6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, —(CH 2 ) a OR a , —(CH 2 ) a NR a R a , —(CH 2 ) a NHOH, —(CH 2 ) a NR a NR a R a , —(CH 2 ) a NO 2 , —(CH 2 ) a CN, —(CH 2 ) a CO 2 R a , —(CH 2 ) a C(O)R a , —(CH 2 ) a OC(O)R a , —(CH 2 ) a CONR a R a , CF 3 , and OCF 3 ; 
         R a  is independently selected from the group consisting of H, C 1 - 6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3 - 8  cycloalkyl, (C 3 - 8  cycloalkyl)C 1 - 8  alkylene, aryl, (aryl)C 1 - 8  alkylene, heteroaryl, and (heteroaryl)C 1 - 8  alkylene, wherein the alkyl and cycloalkyl optionally are interrupted with 1-2 heteroatoms selected from the group consisting of —O—, —S(O) 0-2 — and —NR c —; 
         R 1  is independently selected from the group consisting of H, C 1 - 8  alkyl, C 3 - 8  cycloalkyl, (C 3 - 8  cycloalkyl)C 1 - 8  alkylene, aryl, (aryl)C 1 - 8  alkylene, heteroaryl, (heteroaryl)C 1 - 8  alkylene, (aryl)(aryl)-C 1 - 8  alkylene, (heteroaryl)(heteroaryl)-C 1 - 8  alkylene, and (aryl)(heteroaryl)C 1-8  alkylene, wherein the alkyl and cycloalkyl optionally may be interrupted with 1-2 heteroatoms selected from the group consisting of —O—, —S(O) 0-2 — and —NR c —, and the groups of R 1  are substituted with 0-4 groups independently selected from the group consisting of F, Cl, Br, I, C 1 - 6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, —(CH 2 ) a OR a , —(CH 2 ) a NR a R a , —(CH 2 ) a NHOH, —(CH 2 ) a NR a NR a R a , —(CH 2 ) a NO 2 , —(CH 2 ) a CN, —(CH 2 ) a CO 2 R a , —(CH 2 ) a C(O)R a , —(CH 2 ) a OC(O)R a , —(CH 2 ) a CONR a R a , CF 3 , and OCF 3 ; 
         R 2  is selected from the group consisting of H, C 1-6  alkyl, OR a , N(R a ) 2 , C 3-8  cycloalkyl, aryl, heterocycle, and heteroaryl, wherein the alkyl, cycloalkyl, aryl, heterocycle, and heteroaryl optionally are substituted with 1-2 groups independently selected from the group consisting of F, Cl, I, Br, CH 3 , CF 3 , and CH 3 O; 
         R 3  is absent or is C 1-8  alkylene, wherein the alkylene group optionally is interrupted with 1-2 heteroatoms selected from the group consisting of —O—, —S(O) 0-2 — and —NH—; 
         R 3  is un or is substituted with 1-2 groups selected from the group consisting of F, Cl, Br, I, —OR d , —SR d , —N(R d ) 2 , C 3-6  cycloalkyl, (C 3-6  cycloalkyl)C 1-4  alkylene, aryl, (aryl)C 1 - 4  alkylene, heteroaryl, and (heteroaryl)C 1 - 4  alkylene, wherein the alkyl and cycloalkyl optionally are interrupted by 1-2 heteroatoms selected from the group consisting of —O—, —S(O) 0-2 —, and —NR c —; 
         R 4  is selected from the group consisting of C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, C 3 - 12  cycloalkyl, (C 3-12  cycloalkyl)C 1 - 8  alkylene, aryl, (aryl)C 1 - 8  alkylene, heteroaryl, (heteroaryl)C 1 - 8  alkylene, CF 3 , —CO 2 R b , R b C(O)—, (R b ) 2 NC(O)—, R b OC(S)—, R b C(S)—, and R b S(═O)—, wherein the alkyl and cycloalkyl optionally are interrupted with 1-2 heteroatoms selected from the group consisting of —O—, —S(O) 0-2 — and —NH—, and the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heteroaryl are substituted with 1-4 groups independently selected from the group consisting of F, Cl, Br, I, C 1 - 6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, —(CH 2 ) a OR a , —(CH 2 ) a NR a R a , —(CH 2 ) a NHOH, —(CH 2 ) a NR a NR a R a , —(CH 2 ) a NO 2 , —(CH 2 ) a CN, —(CH 2 ) a CO 2 R a , —(CH 2 ) a C(O)R a , —(CH 2 ) a OC(O)R a , —(CH 2 ) n CONR a R a , CF 3 , OCF 3 , and —OS(O 2 )R a ; 
         alternatively, when R 3  is present, R 4  is additionally selected from the group consisting of H, F, Cl, Br, I, N(R b ) 2 , OR b , SR b , —CN, NO 2 , CF 3 O, R b C(O)O—, —OCO 2 R b , (R b ) 2 NC(O)O—, R b OC(O)NR b —, R b C(O)NR b —, (R b ) 2 NC(O)NR b —, and (R b ) 2 NC(S)NR b —; 
         provided that when R 2  is H and R 3  is absent, then R 4  is other than 
       
       
         
           
           
               
               
           
         
       
       wherein:
   (a) “*” is the point of attachment;   (b) R z  is —CH 2 OR, —CO 2 R, —OC(O)R, —CH 2 OC(O)R, —CH 2 SR, —C(S)OR, —CH 2 OC(S)R, —CH 2 NRR, —C(S)NRR, and, —C(O)NRR; and,   (c) R is H or a substituent;   
 R b  is independently selected from the group consisting of H, C 1 - 6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 3 - 8  cycloalkyl, (C 3 - 8  cycloalkyl)C 1 - 8  alkylene, aryl, (aryl)C 1 - 8  alkylene, heteroaryl, and (heteroaryl)C 1 - 8  alkylene, wherein the alkyl and cycloalkyl optionally are interrupted with 1-2 heteroatoms selected from the group consisting of —O—, —S(O) 0-2 — and —NH— and wherein the alkyl, cycloalkyl, aryl, and heteroaryl are substituted with 0-4 substituents selected from the group consisting of F, Cl, Br, I, C 1 - 6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, —(CH 2 ) a OR a , —(CH 2 ) a NR a R a , —(CH 2 ) a NHOH, —(CH 2 ) a NR a NR a R a , —(CH 2 ) a NO 2 , —(CH 2 ) a CN, —(CH 2 ) a CO 2 R a , —(CH 2 ) a C(O)R a , —(CH 2 ) a OC(O)R a , —(CH 2 ) a CONR a R a , CF 3 , and OCF 3 ; 
 R c  is independently selected from the group consisting of H, C 1 - 6  alkyl, and benzyl; 
 R d  is independently selected from the group consisting of H, C 1 - 6  alkyl, C 3-6  cycloalkyl, (C 3-6  cycloalkyl)C 1-4  alkylene, phenyl, and benzyl; 
 R 5  is independently selected from the group consisting of H, F, Cl, Br, I, —OR c , —N(R c ) 2 , C 1 - 6  alkyl, C 3-6  cycloalkyl, aryl, and (aryl)C 1 - 4  alkylene, wherein the alkyl and cycloalkyl optionally are interrupted by 1-2 heteroatoms selected from the group consisting of —O—, —S(O) 0-2 —, and —NR b —; 
 R 6  is selected from the group consisting of CH 2 CH 2 , CH═CH, and C≡C; 
 a is independently selected from the group consisting of 0, 1, and 2; 
 n is independently selected from the group consisting of 0, 1, and 2; 
 p is independently selected from the group consisting of 0, 1, and 2; 
 q is independently selected from the group consisting of 0, 1, and 2; and, 
 r is independently selected from the group consisting of 0, 1, and 2. 
 
     
     
         2 . The compound according to  claim 1 , wherein the compound is of formula IIa or IIIa: 
       
         
           
           
               
               
           
         
         wherein: 
         Y is selected from the group consisting of O, NY 1 , OCH 2 CH 2 OCH 2 , and, NY 1 CH 2 CH 2 OCH 2 ; 
         alternatively, Y is absent; 
         Y 1  is selected from the group consisting of H and CH 3 ; 
         Z is selected from the group consisting of 5-6 membered heteroaryl and phenyl, wherein Z is attached via a carbon atom and is substituted with 1-4Z 1  groups; 
         Z 1  is independently selected from the group consisting of F, Cl, C 1 - 4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, —(CH 2 ) a OR a , —(CH 2 ) a NR a R a , —(CH 2 ) a NHOH, —(CH 2 ) a NR a NR a R a , —(CH 2 ) a NO 2 , —(CH 2 ) a CN, —(CH 2 ) a CO 2 R a , —(CH 2 ) a C(O)R a , —(CH 2 ) a OC(O)R a , —(CH 2 ) a CONR a R a , CF 3 , and OCF 3 ; 
         R a  is independently selected from the group consisting of H, C 1 - 4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 3 - 6  cycloalkyl, (C 3 - 6  cycloalkyl)C 1 - 2  alkylene, aryl, (aryl)C 1 - 2  alkylene, heteroaryl, and (heteroaryl)C 1 - 2  alkylene, wherein the alkyl and cycloalkyl optionally are interrupted with 1-2 heteroatoms selected from the group consisting of —O—, —S(O) 0-2 — and —NR c —; 
         R 1  is independently selected from the group consisting of H, C 1 - 4  alkyl, C 3-6  cycloalkyl, (C 3 - 6  cycloalkyl)C 1 - 4  alkylene, aryl, (aryl)C 1 - 4  alkylene, heteroaryl, (heteroaryl)C 1 - 4  alkylene, (aryl)(aryl)-C 1 - 4  alkylene, (heteroaryl)(heteroaryl)-C 1 - 4  alkylene, and (aryl)(heteroaryl)C 1-2  alkylene, wherein the alkyl and cycloalkyl optionally are interrupted with 1-2 heteroatoms selected from the group consisting of —O—, —S(O) 0-2 — and —NR c — and the aryl and heteroaryl rings are substituted with 0-2 groups independently selected from the group consisting of F, Cl, C 1 - 4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, —(CH 2 ) a OR a , —(CH 2 ) a NR a R a , —(CH 2 ) a NHOH, —(CH 2 ) a NR a NR a R a , —(CH 2 ) a NO 2 , —(CH 2 ) a CN, —(CH 2 ) a CO 2 R a , —(CH 2 ) a C(O)R a , —(CH 2 ) a OC(O)R a , —(CH 2 ) a CONR a R a , CF 3 , and OCF 3 ; 
         R 2  is selected from the group consisting of H, C 1-4  alkyl, OR a , N(R a ) 2 , C 3-6  cycloalkyl, aryl, heterocycle, and heteroaryl, wherein the alkyl, cycloalkyl, aryl, heterocycle, and heteroaryl are substituted with 0-2 groups independently selected from the group consisting of F, Cl, CH 3 , CF 3 , and CH 3 O; 
         R 4  is selected from the group consisting of C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 3 - 6  cycloalkyl, (C 3-6  cycloalkyl)C 1 - 2  alkylene, aryl, (aryl)C 1 - 2  alkylene, heteroaryl, (heteroaryl)C 1 - 2  alkylene, CF 3 , —CO 2 R b , R b C(O)—, (R b ) 2 NC(O)—, R b OC(S)—, R b C(S)—, and R b S(═O)—, wherein the alkyl and cycloalkyl optionally are interrupted with 1-2 heteroatoms selected from the group consisting of —O—, —S(O) 0-2 — and —NH—, and the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heteroaryl are substituted with 0-3 groups independently selected from the group consisting of F, Cl, C 1 - 4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, —(CH 2 ) a OR a , —(CH 2 ) a NR a R a , —(CH 2 ) a NHOH, —(CH 2 ) a NR a NR a R a , —(CH 2 ) a NO 2 , —(CH 2 ) a CN, —(CH 2 ) a CO 2 R a , —(CH 2 ) a C(O)R a , —(CH 2 ) a OC(O)R a , —(CH 2 ) a CONR a R a , CF 3 , OCF 3 , and —OS(O 2 )R a ; 
         alternatively, when R 3  is at least 1, R 4  additionally may be selected from the group consisting of H, F, Cl, N(R b ) 2 , OR b , SR b , —CN, NO 2 , CF 3 O, R b C(O)O—, —OCO 2 R b , (R b ) 2 NC(O)O—, R b OC(O)NR b —, R b C(O)NR b —, (R b ) 2 NC(O)NR b —, and (R b ) 2 NC(S)NR b —; 
         provided that when R 2  is H and R 3  is absent, then R 4  is other than 
       
       
         
           
           
               
               
           
         
       
       wherein:
   (a) “*” is the point of attachment;   (b) R z  is —CH 2 OR, —CO 2 R, —OC(O)R, —CH 2 OC(O)R, —CH 2 SR, —C(S)OR, —CH 2 OC(S)R, —CH 2 NRR, —C(S)NRR, and, —C(O)NRR; and,   (c) R is H or a substituent;   
 R b  is independently selected from the group consisting of H, C 1 - 4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, C 3 - 6  cycloalkyl, (C 3 - 6  cycloalkyl)C 1 - 2  alkylene, aryl, (aryl)C 1 - 2  alkylene, heteroaryl, and (heteroaryl)C 1 - 2  alkylene, wherein the alkyl and cycloalkyl optionally are interrupted with 1-2 heteroatoms selected from the group consisting of —O—, —S(O) 0-2 — and —NH— and wherein the alkyl, cycloalkyl, aryl, and heteroaryl are substituted with 0-2 substituents selected from the group consisting of F, Cl, C 1 - 4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, —(CH 2 ) a OR a , —(CH 2 ) a NR a R a , —(CH 2 ) a NHOH, —(CH 2 ) a NR a NR a R a , —(CH 2 ) a NO 2 , —(CH 2 ) a CN, —(CH 2 ) a CO 2 R a , —(CH 2 ) a C(O)R a , —(CH 2 ) a OC(O)R a , —(CH 2 ) a CONR a R a , CF 3 , and OCF 3 ; 
 R 3  is absent or is C 1-4  alkylene, wherein the alkylene group optionally is interrupted with a heteroatom selected from the group consisting of —O—, —S(O) 0-2 — and —NH—; 
 R 3  is substituted with 0-1 groups selected from the group consisting of F, Cl, —OR d , —SR d , —N(R d ) 2 , C 3-6  cycloalkyl, (C 3-6  cycloalkyl)C 1-2  alkylene, aryl, (aryl)C 1 - 2  alkylene, heteroaryl, and (heteroaryl)C 1 - 2  alkylene, wherein the alkyl and cycloalkyl optionally are interrupted by 1-2 heteroatoms selected from the group consisting of —O—, —S(O) 0-2 —, and —NR c —; 
 R c  is independently selected from the group consisting of H and C 1 - 4  alkyl; 
 R d  is independently selected from the group consisting of H, C 1 - 4  alkyl, (C 3-6  cycloalkyl)C 1-2  alkylene, and benzyl; 
 R 5  is independently selected from the group consisting of H, F, Cl, —OR c , —N(R c ) 2 , C 1 - 4  alkyl, C 3-6  cycloalkyl, aryl, and (aryl)C 1 - 2  alkylene, wherein the alkyl and cycloalkyl optionally are interrupted by 1 heteroatom selected from the group consisting of —O—, —S(O) 0-2 —, and —NR b —; 
 a is independently selected from the group consisting of 0 and 1; 
 n is independently selected from the group consisting of 0 and 1; 
 p is independently selected from the group consisting of 0 and 1; 
 q is independently selected from the group consisting of 0 and 1; and, 
 r is independently selected from the group consisting of 0 and 1. 
 
     
     
         3 . The compound according to  claim 2 , wherein:
 Y is selected from the group consisting of O and OCH 2 CH 2 OCH 2 ;   alternatively, Y is absent;   Z is selected from the group consisting of phenyl, pyridyl, and pyrimidyl, wherein Z is attached via a carbon atom and is substituted with 1-3Z 1  groups;   Z 1  is independently selected from the group consisting of F, Cl, C 1 - 4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, OR a , NHOH, NR a NR a R a , NO 2 , CO 2 R a , C(O)R a , OC(O)R a , CONR a R a , CF 3 , and OCF 3 ;   R 1  is independently selected from the group consisting of H, C 1 - 4  alkyl, (cyclopropyl)CH 2 —, benzyl, pyridyl-CH 2 —, (phenyl)(phenyl)-C 1 - 4  alkylene, (pyridyl)(pyridyl)-C 1 - 4  alkylene, and (phenyl)(pyridyl)C 1-4  alkylene, wherein the aryl and heteroaryl rings are substituted with 0-2 groups independently selected from the group consisting of F, Cl, CH 3 , OH, OCH 3 , NH 2 , NHCH 3 , N(CH 3 ) 2 , NHOH, NHNH 2 , NO 2 , CN, CO 2 CH 3 , C(O)CH 3 , CONH 2 , C(O)NHCH 3 , C(O)N(CH 3 ) 2 , CF 3 , and OCF 3 ;   R 2  is selected from the group consisting of H, OR a , N(R a ) 2 , phenyl, and 5-6 membered heteroaryl, wherein the aryl, and heteroaryl are substituted with 0-2 groups independently selected from the group consisting of F, Cl, CH 3 , CF 3 , and CH 3 O;   R 3  is absent or is C 1-2  alkylene;   R 4  is selected from the group consisting of C 2-4  alkenyl, C 2-4  alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, heteroaryl, wherein the cycloalkyls optionally are interrupted with a heteroatom selected from the group consisting of —O—, —S(O) 0-2 — and —NH—, and the alkenyl, alkynyl, cycloalkyl, aryl, and heteroaryl are substituted with 0-2 groups independently selected from the group consisting of F, Cl, CH 3 , OH, OCH 3 , NH 2 , NHCH 3 , N(CH 3 ) 2 , NHOH, NHNH 2 , NO 2 , CN, CO 2 CH 3 , C(O)CH 3 , CONH 2 , C(O)NHCH 3 , C(O)N(CH 3 ) 2 , CF 3 , and OCF 3 ;   R 5  is independently selected from the group consisting of H and CH 3 ;   n is 1;   p is 1;   q is independently selected from the group consisting of 0 and 1; and,   r is independently selected from the group consisting of 0 and 1.   
     
     
         4 . The compound according to  claim 3 , wherein:
 Z is selected from the group consisting of phenyl, pyridyl, and pyrimidyl, wherein Z is attached via a carbon atom and is substituted with 1Z 1 group: and,   Z 1  is independently selected from the group consisting of F, Cl, CH 3 , CH 2 CH 3 , OH, OCH 3 , NH 2 , NHCH 3 , N(CH 3 ) 2 , NHOH, NHNH 2 , NO 2 , CN, CO 2 CH 3 , C(O)CH 3 , CONH 2 , C(O)NHCH 3 , C(O)N(CH 3 ) 2 , CF 3 , and OCF 3 .   
     
     
         5 . The compound according to  claim 2 , wherein the compound is of formula IIa. 
     
     
         6 . The compound according to  claim 5 , wherein p is 1. 
     
     
         7 . The compound according to  claim 6 , wherein r is 0. 
     
     
         8 . The compound according to  claim 7 , wherein Y is O. 
     
     
         9 . The compound according to  claim 8 , wherein the compound is of formula IIb: 
       
         
           
           
               
               
           
         
       
     
     
         10 . The compound according to  claim 2 , wherein the compound is of formula IIIa. 
     
     
         11 . The compound according to  claim 10 , wherein p is 1. 
     
     
         12 . The compound according to  claim 11 , wherein r is 0. 
     
     
         13 . The compound according to  claim 12 , wherein Y is O. 
     
     
         14 . The compound according to  claim 13 , wherein the compound is of formula IIIb: 
       
         
           
           
               
               
           
         
       
     
     
         15 . The compound according to  claim 1 , wherein the compound is selected from:
 4-[3-(6-Amino-9-prop-2-ynyl-9H-purin-2-yl)-prop-2-ynyl]-piperidine-1-carboxylic acid 2-benzyloxy-ethyl ester;   4-[3-(6-Amino-9-cyclopentyl-9H-purin-2-yl)-prop-2-ynyl]-piperidine-1-carboxylic acid 2-benzyloxy-ethyl ester;   4-[3-(6-Amino-9-prop-2-ynyl-9H-purin-2-yl)-prop-2-ynyl]-piperidine-1-carboxylic acid 3-trifluoromethyl-phenyl ester;   4-[3-(6-Amino-9-cyclopentyl-9H-purin-2-yl)-prop-2-ynyl]-piperidine-1-carboxylic acid 3-trifluoromethyl-phenyl ester;   4-[3-(6-Amino-9-prop-2-ynyl-9H-purin-2-yl)-prop-2-ynyl]-piperidine-1-carboxylic acid 2-fluoro-phenyl ester;   4-[3-(6-Amino-9-prop-2-ynyl-9H-purin-2-yl)-prop-2-ynyl]-piperidine-1-carboxylic acid 4-nitro-phenyl ester;   4-[3-(6-Amino-9-prop-2-ynyl-9H-purin-2-yl)-prop-2-ynyl]-piperidine-1-carboxylic acid 4-methoxycarbonyl-phenyl ester;   4-[3-(6-Amino-9-prop-2-ynyl-9H-purin-2-yl)-prop-2-ynyl]-piperidine-1-carboxylic acid 4-chloro-phenyl ester;   4-[3-(6-Amino-9-prop-2-ynyl-9H-purin-2-yl)-prop-2-ynyl]-piperidine-1-carboxylic acid 4-methoxy-phenyl ester;   4-[3-(6-Amino-9-prop-2-ynyl-9H-purin-2-yl)-prop-2-ynyl]-piperidine-1-carboxylic acid 4-methyl-phenyl ester;   4-[3-(6-Amino-9-prop-2-ynyl-9H-purin-2-yl)-prop-2-ynyl]-piperidine-1-carboxylic acid 4-nitro-benzyl ester;   4-[3-(6-Amino-9-prop-2-ynyl-9H-purin-2-yl)-prop-2-ynyl]-piperidine-1-carboxylic acid 2-chloro-phenyl ester;   4-[3-(6-Amino-9-prop-2-ynyl-9H-purin-2-yl)-prop-2-ynyl]-piperidine-1-carboxylic acid 2-methoxy-phenyl ester;   2-{3-[1-((3,4-Dimethyl)phenoxycarbanoyl)piperidin-4-yl]propyn-1-yl}-9-propargyladenine;   2-{3-[1-((3,4-Difluoro)phenoxycarbanoyl)piperidin-4-yl]propyn-1-yl}-9-propargyladenine; and,   2-{3-[1-((3,4-Dichloro)phenoxycarbanoyl)piperidin-4-yl]propyn-1-yl)-9-propargyladenine.   
     
     
         16 . The compound according to  claim 1 , wherein the compound is selected from a compound of Table A. 
     
     
         17 . A pharmaceutical composition comprising: a therapeutically effective amount of a compound of any preceding claim and a pharmaceutically acceptable carrier. 
     
     
         18 . A therapeutic method for preventing or treating a pathological condition or symptom in a mammal, wherein the activity of adenosine A 2A  receptors is implicated and antagonism of its action is desired comprising administering to the mammal an effective amount of a compound of  claim 1 . 
     
     
         19 . A method for treating a movement disorder, comprising administering to a subject suffering from a movement disorder associated with unwanted or excessive activity of the adenosine A 2A  receptor a therapeutically effective amount of a compound of  claim 1 . 
     
     
         20 . A method according to  claim 19 , wherein said movement disorder is selected from: Huntington's disease, catalepsy, Parkinson's disease, narcolepsy, progressive supernuclear palsy, multiple system atrophy, corticobasal degeneration, Wilson's disease, Hallervorden-Spatz disease, progressive pallidal atrophy, Dopa-responsive dystonia-Parkinsonism, and spasticity. 
     
     
         21 . A method for treating cancer and/or an addictive disorder (e.g., smoking, alcohol, drugs), comprising administering to a subject afflicted with cancer or an addictive disorder a therapeutically effective amount of a compound of  claim 1 .