Selective antagonists of a2a adenosine receptors

Abstract

Selective antagonists of A 2A adenosine receptors like those of formula I are provided, wherein Y forms a ring. The novel A 2A Blockers are useful for the treatment of Parkinson's disease and other diseases.

1 . A method for treating cancer, comprising: administering a therapeutically effective amount of an A 2A  antagonist compound of formula I a mammal in need of such treatment: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  and R 2  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , (C 1 -C 8 )alkyl, aryl and aryl(C 1 -C 8 )alkyl, wherein R 1  and R 2  are optionally substituted with 1 to 4 substituents of R a , wherein the alkyl is optionally interrupted by 1-4 heteroatoms selected from —O—, —S—, —SO—, S(O) 2 — or amino (—NR a —), or where R 1  and R 2  are independently absent, with the proviso that R a  is not SH or halogen when the R 1  or R 2  to which R a  is bound is halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3  or —SCH 3 ; 
         R 3  is selected from the group consisting of hydrogen, halo, —OR a , —SR a , (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, heterocycle, heterocycle(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, and R a S(═O) 2 —; or if the ring formed from the group CR 3 R 4 R 5  is aryl or heteroaryl or partially unsaturated, then R 3  can be absent; 
         R 4  and R 5  together with the atom to which they are attached form a saturated or partially unsaturated, mono-, bi- or tricyclic or aromatic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR a —) in the ring, wherein any ring comprising R 4  and R 5  is optionally further substituted with from 1 to 14 R 6  groups; wherein each R 6  is independently selected from the group consisting of halo, —OR a , —SR 3 , substituted or unsubstituted (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, heterocycle, heterocyclyl(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R 3 , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , and R a S(═O)— or two R 6  groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R 6  groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring; 
         R 7  and R 8  are each independently hydrogen, (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, aryl aryl(C 1 -C 8 )alkylene, heteroaryl, and heteroaryl(C 1 -C 8 )alkylene; or wherein R 7  and R 8  together with the nitrogen atom to which they attach form a heterocycle or heteroaromatic ring; 
         R 9  and R 10  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , (C 1 -C 8 )alkyl, aryl and aryl(C 1 -C 8 )alkyl, wherein R 9  and R 10  are optionally substituted with 1 to 4 substituents of R a , wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, —SO—, —S(O) 2 — or amino (—NR a —), or where R 9  and R 10  are independently absent, with the proviso that R 3  is not SH or halogen in the case where the R 9  or R 10  to which R a  is bound is halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3  or —SCH 3 ; 
         Y is —CR 3 R 4 R 5  or NR 4 R 5 ; 
         Z is selected from the group consisting of halogen, vinyl, allyl, 1-propenyl, isopropenyl, ethynyl, 1-propynyl, 2-propynyl, 1,3-butadienyl, penta-1,3-dienyl, penta-1,4-dienyl, hexa-1,3-dienyl, hexa-1,3,5-trienyl, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, (C 6 -C 20 )polycyclyl, heterocyclyl, cycloalkyl(C 1 -C 8 )alkyl, bicycloalkyl(C 6 -C 12 )alkyl, heterocyclyl(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —NR a R b , —SR a , cyano, nitro, trifluoromethyl, trifluoromethoxy, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)NR a —, R a R b NC(═O)—, R a C(═O)NR b —, R a R b NC(═O)NR b —, R a R b NC(═S)NR b —, R a OC(═S)—, R a C(═S), —SSR a , R a S(═O), —OS(O 2 )R a , OS(═O)OR a , —OS(O 2 )OR a  and —O(SO 2 )NR a R b ; 
         R a  and R b  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , propargyl, cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3 , —OS(O 2 )OCH 3 , (C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, cycloalkyl(C 1 -C 8 )alkyl, bicycloalkyl(C 6 -C 12 )alkyl, heteroaryl and heteroaryl(C 1 -C 8 )alkyl, wherein the alkyl and cycloalkyl are optionally interrupted with 1-4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — and amino (—NR c —); and wherein the alkyl, cycloalkyl, aryl and heteroaryl are optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of —OR c , —NR c R c , SR c , cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3  and —OS(O 2 )OCH 3 , provided that the point of attachment of R a  or R b  is not a heteroatom when it is attached to another heteroatom; 
         R c  is selected from the group consisting of hydrogen and (C 1 -C 8 )alkyl; and 
         m is 0 to 8; n is 0, 1, 2 or 3, provided that when m is 0, Z is not halogen, cyano, or nitro or is not attached via a heteroatom, and when n is 0, Y is not —NR 4 R 5 ; or 
         a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof. 
       
     
     
         2 . The method of  claim 1 , wherein Z is selected from aryl, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, or (C 6 -C 20 )polycyclyl, wherein the ring atoms are optionally interrupted by 1 to 8 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — and amino (—NR a —). 
     
     
         3 . The method of  claim 1 , wherein R 3  is selected from the group consisting of hydrogen, OH, OCH 3 , OAc, NH 2 , NHCH 3 , N(CH 3 ) 2  and NHAc. 
     
     
         4 . The method of  claim 1 , wherein the ring comprising R 4  and R 5  and the atom to which they are attached is selected from the group consisting of cyclopentane, cyclohexane, piperidine, dihydro-pyridine, tetrahydro-pyridine, pyridine, piperazine, decaline, tetrahydro-pyrazine, dihydro-pyrazine, pyrazine, dihydro-pyrimidine, tetrahydro-pyrimidine, hexahydro-pyrimidine, pyrazine, imidazole, dihydro-imidazole, imidazolidine, pyrazole, dihydro-pyrazole, pyrazolidine, norbornane and adamantane, each unsubstituted or substituted. 
     
     
         5 . The method of  claim 4 , wherein the ring comprising R 4  and R 5  and the atom to which they are attached is selected from the group consisting of cyclohexane, piperidine, piperazine, norbornane, adamantane, each unsubstituted or substituted. 
     
     
         6 . The method of  claim 1 , wherein number of R 6  groups substituted on the R 4 R 5  ring is from 1 to 4 and each R 6  is independently selected from the group consisting of OH, OCH 3 , methyl, ethyl, t-butyl, —CO 2 R 3 , —CON a R b , OAc, NH 2 , NHCH 3 , N(CH 3 ) 2 , NHEt and N(Et) 2 , provided that when the ring comprising R 4  and R 5  contains a ring heteroatom that is O or S, the ring heteroatom that is O or S is not substituted with R 6 . 
     
     
         7 . The method of  claim 1 , wherein —NR 7 R 8  is selected from the group consisting of amino, methylamino, dimethylamino, ethylamino, 3-pentylamino, (diphenylethyl)-amino, (pyridylmethyl)-amino, diethylamino and benzylamino. 
     
     
         8 . The method of  claim 1 , wherein R 9  is independently selected from the group consisting of hydrogen, fluoro, —OH, —CH 2 OH, —OCH 3 , —NH 2 , —NHCH 3 , and —N(CH 3 ) 2 . 
     
     
         9 . The method of  claim 1 , wherein R 10  is hydrogen. 
     
     
         10 . The method of  claim 1 , wherein R a  and R b  are each independently selected from the group consisting of hydrogen, (C 1 -C 4 )alkyl, aryl and aryl(C 1 -C 8 )alkylene. 
     
     
         11 . The method of  claim 1 , wherein Y is —CR 3 R 4 R 5  or NR 4 R 5 , and is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         wherein q is 0, 1, 2, 3 or 4; R 3  is selected from the group consisting of hydrogen, halo, —OR a , —SR a , (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, heterocycle, heterocycle(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, and R a S(═O) 2 —; and each R 6  is independently selected from the group consisting of halo, —OR 3 , —SR a , substituted or unsubstituted (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, heterocycle, heterocyclyl(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R 3 , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , and R a S(═O)—, provided that R 6  is not halogen or a heteroatom when R 6  is attached to a heteroatom. 
       
     
     
         12 . The method of  claim 1 , wherein Y is —CR 3 R 4 R 5  or NR 4 R 5  and is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         wherein R 3  is selected from the group consisting of hydrogen, halo, —OR a , —SR a , (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, heterocycle, heterocycle(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R a OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR 3 , R a S(═O)—, and R a S(═O) 2 —; and each R 6  is independently selected from the group consisting of halo, —OR a , —SR 3 , substituted or unsubstituted (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, heterocycle, heterocyclyl(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , and R a S(═O)—. 
       
     
     
         13 . A method for treating cancer, comprising: administering a therapeutically effective amount of an A 2A  antagonist compound of formula IIa mammal in need of such treatment: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  and R 2  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , (C 1 -C 8 )alkyl, aryl and aryl(C 1 -C 8 )alkyl, wherein R 1  and R 2  are optionally substituted with 1 to 4 substituents of R a , wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, —SO—, —S(O) 2 — or amino (—NR a —), or where R 1  and R 2  are independently absent, with the proviso that R a  is not SH or halogen when the R 1  or R 2  to which R a  is bound is halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3  or —SCH 3 ; 
         R 3  is selected from the group consisting of hydrogen, halo, —OR a , —SR a , (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, heterocycle, heterocycle(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, and R a S(═O) 2 —; or if the ring formed from the group CR 3 R 4 R 5  is aryl or heteroaryl or partially unsaturated, then R 3  can be absent; 
         R 4  and R 5  together with the atom to which they are attached form a saturated or partially unsaturated, mono-, bi- or tricyclic, or aromatic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR c —) in the ring, wherein any ring comprising R 4  and R 5  is optionally further substituted with from 1 to 14 R 6  groups; wherein each R 6  is independently selected from the group consisting of hydrogen, halo, —OR 3 , —SR a , substituted or unsubstituted (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, heterocycle, heterocyclyl(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b —, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , and R a S(═O)—, or two R 6  groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R 6  groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring; 
         R 7  and R 8  are each independently hydrogen, (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, aryl or aryl(C 1 -C 8 )alkylene, heteroaryl, heteroaryl(C 1 -C 8 )alkylene-; or wherein R 7  and R 8  together with the nitrogen atom to which they attach form a heterocycle or heteroaromatic ring; 
         R 9  and R 10  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , (C 1 -C 8 )alkyl, aryl and aryl(C 1 -C 8 )alkyl, wherein R 9  and R 10  are optionally substituted with 1 to 4 substituents of R a , wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, SO—, —S(O) 2 — or amino (—NR a —), or where R 9  and R 10  are independently absent, with the proviso that R a  is not SH or halogen in the case where R 9  and R 10  to which R a  is bound is halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3  and —SCH 3 ; 
         L is a linker selected from the group consisting of —(C 1 -C 3 )alkyl-C≡C—, —C≡C—(C 1 -C 3 )alkyl-, —(CH 2 ) 1-3 —CH═CH—, —CH═CH—(CH 2 ) 1-3 —, —(CH 2 ) 1-2 —CH═CH—CH 2 — and —CH 2 —CH═CH—(CH 2 ) 1-2 —; 
         Y is —CR 3 R 4 R 5  or NR 4 R 5 ; 
         Z is selected from the group consisting of halogen, vinyl, allyl, 1-propenyl, isopropenyl, ethynyl, 1-propynyl, 2-propynyl, 1,3-butadienyl, penta-1,3-dienyl, penta-1,4-dienyl, hexa-1,3-dienyl, hexa-1,3,5-trienyl, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, (C 6 -C 20 )polycyclyl, heterocyclyl, cycloalkyl(C 1 -C 8 )alkyl, bicycloalkyl(C 6 -C 12 )alkyl, heterocyclyl(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —NR a R b , —SR a , cyano, nitro, trifluoromethyl, trifluoromethoxy, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)NR a —, R a R b NC(═O)—, R a C(═O)NR b —, R a R b NC(═O)NR b —, R a R b NC(═S)NR b , R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, —OS(O 2 )R a , —OS(═O)OR a , —OS(O 2 )OR a  and —O(SO 2 )NR a R b ; 
         R a  and R b  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , propargyl, cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3 , —OS(O 2 )OCH 3 , (C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, cycloalkyl(C 1 -C 8 )alkyl, bicycloalkyl(C 6 -C 12 )alkyl, heteroaryl and heteroaryl(C 1 -C 8 )alkyl, wherein the alkyl and cycloalkyl are optionally interrupted with 1 to 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — and amino (—NR c —); and wherein the alkyl, cycloalkyl, aryl and heteroaryl are optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of —OR c , —NR c R c , SR c , cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3  and —OS(O 2 )OCH 3 , provided that the point of attachment of R a  or R b  is not a heteroatom when it is attached to another heteroatom; 
         R c  is selected from the group consisting of hydrogen and (C 1 -C 8 )alkyl; and 
         m is 0 to 8; n is 0, 1, 2 or 3 provided that when m is 0, Z is not halogen, cyano, or nitro or is not attached via or a heteroatom; or 
         a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof. 
       
     
     
         14 . A method for treating cancer, comprising: administering a therapeutically effective amount of an A 2A  antagonist compound of formula I a mammal in need of such treatment: 
       
         
           
           
               
               
           
         
         wherein: 
         (CR 1 R 2 ) m -Z together is selected from the group consisting of —CH 2 CH═CH 2 , —CH 2 C≡CH, —CH 2 C≡CCH 3  or —CH 2 CH 2 C≡CH; 
         Y is —CR 3 R 4 R 5  or NR 4 R 5 ; 
         R 3  is selected from the group consisting of hydrogen, halo, —OR a , —SR a , (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, heterocycle, heterocycle(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, and R a S(═O) 2 —; or if the ring formed from the group CR 3 R 4 R 5  is aryl or heteroaryl or partially unsaturated, then R 3  can be absent; 
         R 4  and R 5  together with the atom to which they are attached form a saturated or partially unsaturated, mono-, bi- or tricyclic or aromatic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR a —) in the ring, wherein any ring comprising R 4  and R 5  is optionally further substituted with from 1 to 14 R 6  groups; wherein each R 6  is independently selected from the group consisting of halo, —OR a , —SR 3 , substituted or unsubstituted (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, heterocycle, heterocyclyl(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , and R a S(═O)—, or two R 6  groups and the atom to which they are attached combine to form C═O or C═S, or wherein two R 6  groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring; 
         R 7  and R 8  are each independently hydrogen, (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, aryl or aryl(C 1 -C 8 )alkylene, heteroaryl, heteroaryl(C 1 -C 8 )alkylene-; or wherein R 7  and R 8  together with the nitrogen atom to which they attach form a heterocycle or heteroaromatic ring; 
         R 9  and R 10  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , (C 1 -C 8 )alkyl, aryl and aryl(C 1 -C 8 )alkyl, wherein R 9  and R 10  are optionally substituted with 1 to 4 substituents of R a , wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, —SO—, —S(O) 2 — or amino (—NR a —), or where R 9  and R 10  are independently absent, with the proviso that R a  is not SH or halogen in the case where the R 9  or R 10  to which R a  is bound is halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3  or —SCH 3 ; 
         R a  and R b  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , propargyl, cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3 , —OS(O 2 )OCH 3 , (C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, cycloalkyl(C 1 -C 8 )alkyl, bicycloalkyl(C 6 -C 12 )alkyl, heteroaryl and heteroaryl(C 1 -C 8 )alkyl, wherein the alkyl and cycloalkyl are optionally interrupted with 1-4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — and amino (—NR c —); and wherein the alkyl, cycloalkyl, aryl and heteroaryl are optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of —OR a , —NR c R c , SR c , cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3  and —OS(O 2 )OCH 3 , provided that the point of attachment of R a  or R b  is not a heteroatom when it is attached to another heteroatom; 
         R c  is selected from the group consisting of hydrogen and (C 1 -C 8 )alkyl; and 
         n is 0, 1, 2 or 3; or 
         a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof. 
       
     
     
         15 . A method for treating cancer, comprising: administering a therapeutically effective amount of an A 2A  antagonist compound of formula I a mammal in need of such treatment: 
       
         
           
           
               
               
           
         
         wherein 
         Z is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl ring optionally substituted with 1 to 4 substituents of R a ; 
         Y is —CR 3 R 4 R 5  or NR 4 R 5 ; 
         R 1  and R 2  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , (C 1 -C 8 )alkyl, aryl and aryl(C 1 -C 8 )alkyl, wherein R 1  and R 2  are optionally substituted with 1 to 4 substituents of R a , wherein the alkyl is optionally interrupted by 1-4 heteroatoms selected from —O—, —S—, —SO—, —S(O) 2 — or amino (—NR a ), or where R 1  and R 2  are independently absent, with the proviso that R a  is not SH or halogen when the R 1  or R 2  to which R a  is bound is halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3  or —SCH 3 ; 
         R 3  is selected from the group consisting of hydrogen, halo, —OR a , —SR a , (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, heterocycle, heterocycle(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b —, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, and R a S(═O) 2 —; or if the ring formed from the group CR 3 R 4 R 5  is aryl or heteroaryl or partially unsaturated, then R 3  can be absent; 
         R 4  and R 5  together with the atom to which they are attached form a saturated or partially unsaturated, mono-, bi- or tricyclic or aromatic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR a —) in the ring, wherein any ring comprising R 4  and R 5  is optionally further substituted with from 1 to 14 R 6  groups; wherein each R 6  is independently selected from the group consisting of halo, —OR a , —SR a , substituted or unsubstituted (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, heterocycle, heterocyclyl(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , and R a S(═O)— or two R 6  groups and the atom to which they are attached combine to form C═O or C═S, or wherein two R 6  groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring; 
         R 7  and R 8  are each independently hydrogen, (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, aryl or aryl(C 1 -C 8 )alkylene, heteroaryl, heteroaryl(C 1 -C 8 )alkylene-; or wherein R 7  and R 8  together with the nitrogen atom to which they attach form a heterocycle or heteroaromatic ring; 
         R 9  and R 10  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , (C 1 -C 8 )alkyl, aryl and aryl(C 1 -C 8 )alkyl, wherein R 9  and R 10  are optionally substituted with 1 to 4 substituents of R a , wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, —SO—, —S(O) 2 — or amino (—NR a —), or where R 9  and R 10  are independently absent, with the proviso that R a  is not SH or halogen in the case where the R 9  or R 10  to which R a  is bound is halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3  or —SCH 3 ; 
         R a  and R b  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , propargyl, cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3 , —OS(O 2 )OCH 3 , (C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, cycloalkyl(C 1 -C 8 )alkyl, bicycloalkyl(C 6 -C 12 )alkyl, heteroaryl and heteroaryl(C 1 -C 8 )alkyl, wherein the alkyl and cycloalkyl are optionally interrupted with 1-4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, S(O) 2 — and amino (—NR c —); and wherein the alkyl, cycloalkyl, aryl and heteroaryl are optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of —OR c , —NR c R c , SR c , cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3  and —OS(O 2 )OCH 3 , provided that the point of attachment of R a  or R b  is not a heteroatom when it is attached to another heteroatom; 
         R c  is selected from the group consisting of hydrogen and (C 1 -C 8 )alkyl; and 
         m is 0 to 8; n is 0, 1, 2 or 3, provided that when n is 0, Y is not —NR 4 R 5 ; or 
         a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof. 
       
     
     
         16 . The method of  claim 15 , wherein Z is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, where m is 0 or 1. 
     
     
         17 . The method of  claim 1 , wherein:
 Y is selected from the group consisting of   
       
         
           
           
               
               
           
         
         wherein Y optionally comprises 1, 2 or 3 double bonds; each carbon in the ring is optionally replaced by or interrupted by 1 to 6 heteroatoms selected from —O—, —S—, —SO—, S(O) 2 —, or amino (—NR a —), and is optionally further substituted with from 1 to 10 R 6  groups, provided that the Y ring is not attached at a bridgehead carbon atom or at a trisubstituted carbon atom; 
         Z is selected from the group consisting of halogen, vinyl, allyl, 1-propenyl, isopropenyl, ethynyl, 1-propynyl, 2-propynyl, 1,3-butadienyl, penta-1,3-dienyl, penta-1,4-dienyl, hexa-1,3-dienyl, hexa-1,3,5-trienyl, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, (C 6 -C 20 )polycyclyl, heterocyclyl, cycloalkyl(C 1 -C 8 )alkyl, bicycloalkyl(C 6 -C 12 )alkyl, heterocyclyl(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —NR a R b , —SR 3 , cyano, nitro, trifluoromethyl, trifluoromethoxy, —CO 2 R 3 , R a C(═O)—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)NR a —, R a R b NC(═O)—, R a C(═O)NR b —, R a R b NC(═O)NR 1 —, R a R b NC(═S)NR b —, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, —OS(O 2 )R a , —OS(═O)OR a , —OS(O 2 )OR a  and —O(SO 2 )NR a R b ; 
         R 1  and R 2  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , (C 1 -C 8 )alkyl, aryl and aryl(C 1 -C 8 )alkyl, wherein R 1  and R 2  are optionally substituted with 1 to 4 substituents of R a , wherein the alkyl is optionally interrupted by 1-4 heteroatoms selected from —O—, —S—, —SO—, S(O) 2 — or amino (—NR a —), or where R 1  and R 2  are independently absent, with the proviso that R a  is not SH or halogen when the R 1  or R 2  to which R a  is bound is halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3  or —SCH 3 ; 
         R 6  is independently selected from the group consisting of halo, —OR a , —SR a , substituted or unsubstituted (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, heterocycle, heterocyclyl(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , and R a S(═O)— or two R 6  groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R 6  groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring; 
         R 7  and R 8  are each independently hydrogen, (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, aryl or aryl(C 1 -C 8 )alkylene, heteroaryl, heteroaryl(C 1 -C 8 )alkylene-; or wherein R 7  and R 8  together with the nitrogen atom to which they attach form a heterocycle or heteroaromatic ring; 
         R 9  and R 10  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , (C 1 -C 8 )alkyl, aryl and aryl(C 1 -C 8 )alkyl, wherein R 9  and R 10  are optionally substituted with 1 to 4 substituents of R a , wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, —SO—, —S(O) 2 — or amino (—NR a —), or where R 9  and R 10  are independently absent, with the proviso that R a  is not SH or halogen in the case where the R 9  or R 10  to which R a  is bound is halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3  or —SCH 3 ; 
         R a  and R b  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , propargyl, cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3 , —OS(O 2 )OCH 3 , (C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, cycloalkyl(C 1 -C 8 )alkyl, bicycloalkyl(C 6 -C 12 )alkyl, heteroaryl and heteroaryl(C 1 -C 8 )alkyl, wherein the alkyl and cycloalkyl are optionally interrupted with 1-4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — and amino (—NR c —); and wherein the alkyl, cycloalkyl, aryl and heteroaryl are optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of —OR c , —NR c R c , SR c , cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3  and —OS(O 2 )OCH 3 , provided that the point of attachment of R a  or R b  is not a heteroatom when it is attached to another heteroatom; 
         R c  is selected from the group consisting of hydrogen and (C 1 -C 8 )alkyl; and 
         m is 0 to 8; n is 0, 1, 2 or 3, provided that when m is 0, Z is not halogen, cyano, or nitro or attached via a heteroatom; or 
         a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof. 
       
     
     
         18 . A method for treating cancer, comprising: administering a therapeutically effective amount of an A 2A  antagonist compound of formula I a mammal in need of such treatment: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  and R 2  are hydrogen, m is 0, 1, 2 or 3 and Z is the moiety derived from the ring selected from the group consisting of furan, dihydro-furan, thiophene, pyrrole, 2H-pyrrole, 2-pyrroline, 3-pyrroline, pyrrolidine, 1,3-dioxolane, oxazole, thiazole, imidazole, dihydro-imidazole, 2-imidazoline, imidazolidine, pyrazole, 2-pyrazoline, pyrazolidine, isoxazole, isothiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,3-triazole, 1,2,4-triazole, 1,3,4-thiadiazole, 2H-pyran, 1H-tetrazole, 4H-pyran, pyridine, dihydro-pyridine, tetrahydro-pyridine, piperidine, 1,4-dioxane, morpholine, 1,4-dithiane, thiomorpholine, pyridazine, pyrimidine, dihydro-pyrimidine, tetrahydro-pyrimidine, hexahydro-pyrimidine, pyrazine, dihydro-pyrazine, tetrahydro-pyrazine, piperazine, 1,3,5-triazine and 1,3,5-trithiane, wherein each Z group is optionally substituted with from 1 to 10 R a  groups; 
         Y is —CR 3 R 4 R 5  or NR 4 R 5 ; 
         R 3  is selected from the group consisting of hydrogen, halo, —OR a , —SR a , (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, heterocycle, heterocycle(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, and R a S(═O) 2 —; or if the ring formed from the group CR 3 R 4 R 5  is aryl or heteroaryl or partially unsaturated, then R 3  can be absent; 
         R 4  and R 5  together with the atom to which they are attached form a saturated or partially unsaturated, mono-, bi- or tricyclic or aromatic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR a —) in the ring, wherein any ring comprising R 4  and R 5  is optionally further substituted with from 1 to 14 R 6  groups; wherein each R 6  is independently selected from the group consisting of halo, —OR a , —SR a , substituted or unsubstituted (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, heterocycle, heterocyclyl(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , and R a S(═O)— or two R 6  groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R 6  groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring; 
         R 7  and R 8  are each independently hydrogen, (C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, aryl or aryl(C 1 -C 8 )alkylene, heteroaryl, heteroaryl(C 1 -C 8 )alkylene-; or wherein R 7  and R 8  together with the nitrogen atom to which they attach form a heterocycle or heteroaromatic ring; 
         R 9  and R 10  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , (C 1 -C 8 )alkyl, aryl and aryl(C 1 -C 8 )alkyl, wherein R 9  and R 10  are optionally substituted with 1 to 4 substituents of R a , wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, —SO—, —S(O) 2 — or amino (—NR a —), or where R 9  and R 10  are independently absent, with the proviso that R a  is not SH or halogen in the case where the R 9  or R 10  to which R a  is bound is halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3  or —SCH 3 ; 
         R a  and R b  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , propargyl, cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3 , —OS(O 2 )OCH 3 , (C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, cycloalkyl(C 1 -C 8 )alkyl, bicycloalkyl(C 6 -C 12 )alkyl, heteroaryl and heteroaryl(C 1 -C 8 )alkyl, wherein the alkyl and cycloalkyl are optionally interrupted with 1-4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — and amino (—NR c —); and wherein the alkyl, cycloalkyl, aryl and heteroaryl are optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of —OR c , —NR c R c , SR c , cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3  and —OS(O 2 )OCH 3 , provided that the point of attachment of R a  or R b  is not a heteroatom when it is attached to another heteroatom; 
         R c  is selected from the group consisting of hydrogen and (C 1 -C 8 )alkyl; and 
         m is 0 to 8; n is 0, 1, 2 or 3, provided that when m is 0, Z is not attached via a heteroatom, and when n is 0, Y is not —NR 4 R 5 ; or 
         a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof. 
       
     
     
         19 . The method of  claim 18 , wherein R 1  and R 2  are hydrogen, m is 0 or 1, and Z is the moiety derived from the ring selected from the group consisting of furan, thiophene, pyrrole, 2H-pyrrole, oxazole, thiazole, imidazole, pyrazole, isoxazole, isothiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,3-triazole, 1,2,4-triazole, 1,3,4-thiadiazole and 1H-tetrazole, wherein each Z group is optionally substituted with from 1 to 3 R a  groups selected from the group consisting of methyl, ethyl, propyl, iso-propyl, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3  and —SCH 3 . 
     
     
         20 . A method for treating cancer, comprising: administering a therapeutically effective amount of an A 2A  antagonist compound of formula I a mammal in need of such treatment: 
       
         
           
           
               
               
           
         
         wherein: 
         R 7  and R 8  are each independently selected from the group consisting of hydrogen, (C 1 -C 8 )alkyl-, aryl(C 1 -C 8 )alkylene-, mono- or bicyclic-, aromatic or nonaromatic ring having 3, 4, 5, 6, 7, 8, 9 or 10 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR a —) in the ring, and each is optionally substituted with from 1, 2, 3 or 4 R a  groups; 
         Y is —CR 3 R 4 R 5  or NR 4 R 5 ; 
         Z is selected from the group consisting of halogen, vinyl, allyl, 1-propenyl, isopropenyl, ethynyl, 1-propynyl, 2-propynyl, 1,3-butadienyl, penta-1,3-dienyl, penta-1,4-dienyl, hexa-1,3-dienyl, hexa-1,3,5-trienyl, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, (C 6 -C 20 )polycyclyl, heterocyclyl, cycloalkyl(C 1 -C 8 )alkyl, bicycloalkyl(C 6 -C 12 )alkyl, heterocyclyl(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —NR a R b , —SR a , cyano, nitro, trifluoromethyl, trifluoromethoxy, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)NR a —, R a R b NC(═O)—, R a C(═O)NR b —, R a R b NC(═O)NR b —, R a R b NC(═S)NR b —, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, —OS(O 2 )R a , OS(═O)OR a , —OS(O 2 )OR a  and —O(SO 2 )NR a R b ; 
         R 1  and R 2  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , (C 1 -C 8 )alkyl, aryl and aryl(C 1 -C 8 )alkyl, wherein R 1  and R 2  are optionally substituted with 1 to 4 substituents of R a , wherein the alkyl is optionally interrupted by 1-4 heteroatoms selected from —O—, —S—, —SO—, —S(O) 2 — or amino (—NR a ), or where R 1  and R 2  are independently absent, with the proviso that R a  is not SH or halogen when the R 1  or R 2  to which R a  is bound is halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3  or —SCH 3 ; 
         R 3  is selected from the group consisting of hydrogen, halo, —OR a , —SR a , (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, heterocycle, heterocycle(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, and R a S(═O) 2 —; or if the ring formed from the group CR 3 R 4 R 5  is aryl or heteroaryl or partially unsaturated, then R 3  can be absent; 
         R 4  and R 5  together with the atom to which they are attached form a saturated or partially unsaturated, mono-, bi- or tricyclic or aromatic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR a —) in the ring, wherein any ring comprising R 4  and R 5  is optionally further substituted with from 1 to 14 R 6  groups; wherein each R 6  is independently selected from the group consisting of halo, —OR a , —SR a , substituted or unsubstituted (C 1 -C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, heterocycle, heterocyclyl(C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, heteroaryl, heteroaryl(C 1 -C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b —, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , and R a S(═O)— or two R 6  groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R 6  groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring; 
         R 9  and R 10  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , (C 1 -C 8 )alkyl, aryl and aryl(C 1 -C 8 )alkyl, wherein R 9  and R 10  are optionally substituted with 1 to 4 substituents of R a , wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, —SO—, —S(O) 2 — or amino (—NR a —), or where R 9  and R 10  are independently absent, with the proviso that R 3  is not SH or halogen in the case where the R 9  or R 10  to which R a  is bound is halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3  or —SCH 3 ; 
         R a  and R b  are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , propargyl, cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3 , —OS(O 2 )OCH 3 , (C 1 -C 8 )alkyl, aryl, aryl(C 1 -C 8 )alkyl, (C 3 -C 8 )cycloalkyl, (C 6 -C 12 )bicycloalkyl, cycloalkyl(C 1 -C 8 )alkyl, bicycloalkyl(C 6 -C 12 )alkyl, heteroaryl and heteroaryl(C 1 -C 8 )alkyl, wherein the alkyl and cycloalkyl are optionally interrupted with 1-4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — and amino (—NR c —); and wherein the alkyl, cycloalkyl, aryl and heteroaryl are optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of —OR c , —NR c R c , SR c , cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3  and —OS(O 2 )OCH 3 , provided that the point of attachment of R a  or R b  is not a heteroatom when it is attached to another heteroatom; 
         R c  is selected from the group consisting of hydrogen and (C 1 -C 8 )alkyl; and 
         m is 0 to 8; n is 0, 1, 2 or 3, provided that when m is 0, Z is not halogen, cyano, or nitro or is not attached via a heteroatom, and when n is 0, Y is not —NR 4 R 5 ; or 
         a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof. 
       
     
     
         21 . The method of  claim 20 , wherein R 7  is selected from the group consisting of benzyl, phenethyl, phenylpropyl and each is optionally substituted with from 1, 2 or 3 substituents of R a . 
     
     
         22 . The method of  claim 1 , wherein the compound selected from the group: 
       9-Cyclopropylmethyl-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}adenine (1); 
       2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-propargyladenine (2); 
       9-Cyclopentyl-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}adenine (3); 
       9-Cyanomethyl-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}adenine (4); 
       2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-(4-methoxybenzyl)adenine (5); 
       9-(3,4-Dichlorobenzyl)-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}adenine (6); 
       2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-(4-trifluoromethylbenzyl)adenine (7); 
       9-(3,5-Dimethyl-isoxazol-4-ylmethyl)-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}adenine (8); 
       2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-[2-(trifluoromethylphenyl)thiazol-4-ylmethyl]adenine (9); 
       2-{2-[Hydroxy-adamantan-2-yl]ethyn-1-yl}-9-(3-(thiophen-2-yl)prop-2-ynyl)adenine (10); 
       9-Cyclopropylmethyl-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N-6-(3-pentyl)adenine (14); 
       9-Cyclopentyl-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N-6-(3-pentyl)adenine (15); 
       9-Allyl-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N-6-(3-pentyl)adenine (16); 
       2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N-6-(3-pentyl)-9-(propargyl)adenine (17); 
       2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N-6-(3-pentyl)-9-(pent-4-ynyl)adenine (18); 
       9-(2-Chloroethyl)-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N-6-(3-pentyl)adenine (21); 
       9-([1,3]-Dioxolan-2-ylmethyl)-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N-6-(3-pentyl)adenine (22); 
       2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N-6-(3-pentyl)-9-(tetrahydro-pyran-2-ylmethyl)adenine (23); 
       2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N-6-(3-pentyl)-9-(isopropylcarboxylate)adenine (24); 
       9-(Acetic acid ethyl ester)-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N-6-(3-pentyl)adenine (25); 
       2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-(2-oxo-oxazolidin-5-ylmethyl)-N-6-(3-pentyl)adenine (26); 
       9-Benzyl-2-{2-[1(S)-hydroxy-3 (R)-methyl-1-cyclohexyl]ethyn-1-yl}-N-6-(3-pentyl)adenine (27); 
       2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N-6-(3-pentyl)-9-(pyridin-3-ylmethyl)adenine (28); 
       2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-(4-nitrobenzyl)-N-6-(3-pentyl)adenine (29); 
       9-(3,5-Dimethyl-isoxazol-4-ylmethyl)-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N-6-(3-pentyl)adenine (30); 
       2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-(2-methyl-thiazol-5-ylmethyl)-N-6-(3-pentyl)adenine (31); 
       N6-[(S)-(+)-sec-Butyl]-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-propargyl-adenine (32); 
       N6-[(s)-(+)-sec-Butyl]-9-(3,5-dimethyl-isoxazol-4-ylmethyl)-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}adenine (33); 
       2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N-6-[(s)-(−)-alpha-napthalen-1-yl-ethyl]-9-(propargyl)adenine (35); 
       2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N-6-(3-methoxybenzyl)-9-(propargyl)adenine (36); 
       2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-(propargyl)-N-6-(pyridin-2-ylmethyl)adenine (37); 
       2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N-6-[(methyl)(2-phenethyl)]-9-(propargyl)adenine (38); 
       9-Cyclopropylmethyl-2-{2-[hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (45); 
       9-Cyclobutylmethyl-2-{2-[hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (46); 
       9-Cyclopentylmethyl-2-{2-[hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (47); 
       9-Cyclohexylmethyl-2-{2-[hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (48); 
       9-Cyclobutyl-2-{2-[hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (49); 
       9-Cyclopentyl-2-{2-[hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (50); 
       2-{2-[Hydroxy-adamantan-2-yl]ethyn-1-yl}-9-propargyl-adenine (51); 
       2-{2-[Hydroxy-norbornan-2-yl]ethyn-1-yl}-9-propargyladenine; 
       9-(But-3-ynyl)-2-{2-[hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (62); and 
       2-{3-[1-(Methoxycarbanoyl)piperidin-4-yl]propyn-1-yl}-9-propargyladenine (63); or 
       a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.