Selective antagonists of a2a adenosine receptors

A method for treating cancer, comprising:

• administering a therapeutically effective amount of an A2A antagonist compound of formula IIa mammal in need of such treatment:
• wherein:
• R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3, —SCH3, (C1-C8)alkyl, aryl and aryl(C1-C8)alkyl, wherein R1 and R2 are optionally substituted with 1 to 4 substituents of Ra, wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, —SO—, —S(O)2— or amino (—NRa—), or where R1 and R2 are independently absent, with the proviso that Ra is not SH or halogen when the R1 or R2 to which Ra is bound is halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3 or —SCH3;
• R3 is selected from the group consisting of hydrogen, halo, —ORa, —SRa, (C1-C8)alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C3-C8)cycloalkyl, heterocycle, heterocycle(C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, heteroaryl, heteroaryl(C1-C8)alkyl, —CO2Ra, RaC(═O)O—, RaC(═O)—, —OCO2Ra, RaRbNC(═O)O—, RbOC(═O)N(Ra)—, RaRbN—, RaRbNC(═O)—, RaC(═O)N(Rb)—, RaRbNC(═O)N(Rb)—, RaRbNC(═S)N(Rb)—, RaOC(═S)—, RaC(═S)—, —SSRa, RaS(═O)—, and RaS(═O)2—;
• or if the ring formed from the group CR3R4R5 is aryl or heteroaryl or partially unsaturated, then R3 can be absent;
• R4 and R5 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 (—NRc—) in the ring, wherein any ring comprising R4 and R5 is optionally further substituted with from 1 to 14 R6 groups;
• wherein each R6 is independently selected from the group consisting of hydrogen, halo, —OR3, —SRa, substituted or unsubstituted (C1-C8)alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C3-C8)cycloalkyl, (C6-C12)bicycloalkyl, heterocycle, heterocyclyl(C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, heteroaryl, heteroaryl(C1-C8)alkyl, —CO2Ra, RaC(═O)O—, RaC(═O)—, —OCO2Ra, RaRbNC(═O)O—, RbOC(═O)N(Ra)—, RaRb—, RaRbNC(═O)—, RaC(═O)N(Rb)—, RaRbNC(═O)N(Rb)—, RaRbNC(═S)N(Rb)—, RaOC(═S)—, RaC(═S)—, —SSRa, and RaS(═O)—, or two R6 groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R6 groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring;
• R7 and R8 are each independently hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, aryl or aryl(C1-C8)alkylene, heteroaryl, heteroaryl(C1-C8)alkylene-;
• or wherein R7 and R8 together with the nitrogen atom to which they attach form a heterocycle or heteroaromatic ring;
• R9 and R10 are each independently selected from the group consisting of hydrogen, halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3, —SCH3, (C1-C8)alkyl, aryl and aryl(C1-C8)alkyl, wherein R9 and R10 are optionally substituted with 1 to 4 substituents of Ra, wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, SO—, —S(O)2— or amino (—NRa—), or where R9 and R10 are independently absent, with the proviso that Ra is not SH or halogen in the case where R9 and R10 to which Ra is bound is halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3 and —SCH3;
• L is a linker selected from the group consisting of —(C1-C3)alkyl-C≡C—, —C≡C—(C1-C3)alkyl-, —(CH2)1-3—CH═CH—, —CH═CH—(CH2)1-3—, —(CH2)1-2—CH═CH—CH2— and —CH2—CH═CH—(CH2)1-2—;
• Y is —CR3R4R5 or NR4R5;
• 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, (C3-C8)cycloalkyl, (C6-C12)bicycloalkyl, (C6-C20)polycyclyl, heterocyclyl, cycloalkyl(C1-C8)alkyl, bicycloalkyl(C6-C12)alkyl, heterocyclyl(C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, heteroaryl, heteroaryl(C1-C8)alkyl, —NRaRb, —SRa, cyano, nitro, trifluoromethyl, trifluoromethoxy, —CO2Ra, RaC(═O)O—, RaC(═O)—, —OCO2Ra, RaRbNC(═O)O—, RbOC(═O)NRa—, RaRbNC(═O)—, RaC(═O)NRb—, RaRbNC(═O)NRb—, RaRbNC(═S)NRb, RaOC(═S)—, RaC(═S)—, —SSRa, RaS(═O)—, —OS(O2)Ra, —OS(═O)ORa, —OS(O2)ORa and —O(SO2)NRaRb;
• Ra and Rb are each independently selected from the group consisting of hydrogen, halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3, —SCH3, propargyl, cyano, —OS(O2)H, —OS(O2)OH, —OS(O2)CH3, —OS(O2)OCH3, (C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, (C3-C8)cycloalkyl, (C6-C12)bicycloalkyl, cycloalkyl(C1-C8)alkyl, bicycloalkyl(C6-C12)alkyl, heteroaryl and heteroaryl(C1-C8)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 (—NRc—);
• and wherein the alkyl, cycloalkyl, aryl and heteroaryl are optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of —ORc, —NRcRc, SRc, cyano, —OS(O2)H, —OS(O2)OH, —OS(O2)CH3 and —OS(O2)OCH3, provided that the point of attachment of Ra or Rb is not a heteroatom when it is attached to another heteroatom;
• Rc is selected from the group consisting of hydrogen and (C1-C8)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.

A method for treating cancer, comprising:

• administering a therapeutically effective amount of an A2A antagonist compound of formula I a mammal in need of such treatment:
• wherein:
• (CR1R2)m-Z together is selected from the group consisting of —CH2CH═CH2, —CH2C≡CH, —CH2C≡CCH3 or —CH2CH2C≡CH;
• Y is —CR3R4R5 or NR4R5;
• R3 is selected from the group consisting of hydrogen, halo, —ORa, —SRa, (C1-C8)alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C3-C8)cycloalkyl, heterocycle, heterocycle(C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, heteroaryl, heteroaryl(C1-C8)alkyl, —CO2Ra, RaC(═O)O—, RaC(═O)—, —OCO2Ra, RaRbNC(═O)O—, RbOC(═O)N(Ra)—, RaRbN—, RaRbNC(═O)—, RaC(═O)N(Rb)—, RaRbNC(═O)N(Rb)—, RaRbNC(═S)N(Rb)—, RaOC(═S)—, RaC(═S)—, —SSRa, RaS(═O)—, and RaS(═O)2—;
• or if the ring formed from the group CR3R4R5 is aryl or heteroaryl or partially unsaturated, then R3 can be absent;
• R4 and R5 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 (—NRa—) in the ring, wherein any ring comprising R4 and R5 is optionally further substituted with from 1 to 14 R6 groups;
• wherein each R6 is independently selected from the group consisting of halo, —ORa, —SR3, substituted or unsubstituted (C1-C8)alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C3-C8)cycloalkyl, (C6-C12)bicycloalkyl, heterocycle, heterocyclyl(C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, heteroaryl, heteroaryl(C1-C8)alkyl, —CO2Ra, RaC(═O)O—, RaC(═O)—, —OCO2Ra, RaRbNC(═O)O—, RbOC(═O)N(Ra)—, RaRbN—, RaRbNC(═O)—, RaC(═O)N(Rb)—, RaRbNC(═O)N(Rb)—, RaRbNC(═S)N(Rb)—, RaOC(═S)—, RaC(═S)—, —SSRa, and RaS(═O)—, or two R6 groups and the atom to which they are attached combine to form C═O or C═S, or wherein two R6 groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring;
• R7 and R8 are each independently hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, aryl or aryl(C1-C8)alkylene, heteroaryl, heteroaryl(C1-C8)alkylene-;
• or wherein R7 and R8 together with the nitrogen atom to which they attach form a heterocycle or heteroaromatic ring;
• R9 and R10 are each independently selected from the group consisting of hydrogen, halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3, —SCH3, (C1-C8)alkyl, aryl and aryl(C1-C8)alkyl, wherein R9 and R10 are optionally substituted with 1 to 4 substituents of Ra, wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, —SO—, —S(O)2— or amino (—NRa—), or where R9 and R10 are independently absent, with the proviso that Ra is not SH or halogen in the case where the R9 or R10 to which Ra is bound is halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3 or —SCH3;
• Ra and Rb are each independently selected from the group consisting of hydrogen, halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3, —SCH3, propargyl, cyano, —OS(O2)H, —OS(O2)OH, —OS(O2)CH3, —OS(O2)OCH3, (C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, (C3-C8)cycloalkyl, (C6-C12)bicycloalkyl, cycloalkyl(C1-C8)alkyl, bicycloalkyl(C6-C12)alkyl, heteroaryl and heteroaryl(C1-C8)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 (—NRc—);
• and wherein the alkyl, cycloalkyl, aryl and heteroaryl are optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of —ORa, —NRcRc, SRc, cyano, —OS(O2)H, —OS(O2)OH, —OS(O2)CH3 and —OS(O2)OCH3, provided that the point of attachment of Ra or Rb is not a heteroatom when it is attached to another heteroatom;
• Rc is selected from the group consisting of hydrogen and (C1-C8)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.

A method for treating cancer, comprising:

• administering a therapeutically effective amount of an A2A 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 Ra;
• Y is —CR3R4R5 or NR4R5;
• R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3, —SCH3, (C1-C8)alkyl, aryl and aryl(C1-C8)alkyl, wherein R1 and R2 are optionally substituted with 1 to 4 substituents of Ra, wherein the alkyl is optionally interrupted by 1-4 heteroatoms selected from —O—, —S—, —SO—, —S(O)2— or amino (—NRa), or where R1 and R2 are independently absent, with the proviso that Ra is not SH or halogen when the R1 or R2 to which Ra is bound is halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3 or —SCH3;
• R3 is selected from the group consisting of hydrogen, halo, —ORa, —SRa, (C1-C8)alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C3-C8)cycloalkyl, heterocycle, heterocycle(C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, heteroaryl, heteroaryl(C1-C8)alkyl, —CO2Ra, RaC(═O)O—, RaC(═O)—, —OCO2Ra, RaRbNC(═O)O—, RbOC(═O)N(Ra)—, RaRb—, RaRbNC(═O)—, RaC(═O)N(Rb)—, RaRbNC(═O)N(Rb)—, RaRbNC(═S)N(Rb)—, RaOC(═S)—, RaC(═S)—, —SSRa, RaS(═O)—, and RaS(═O)2—;
• or if the ring formed from the group CR3R4R5 is aryl or heteroaryl or partially unsaturated, then R3 can be absent;
• R4 and R5 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 (—NRa—) in the ring, wherein any ring comprising R4 and R5 is optionally further substituted with from 1 to 14 R6 groups;
• wherein each R6 is independently selected from the group consisting of halo, —ORa, —SRa, substituted or unsubstituted (C1-C8)alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C3-C8)cycloalkyl, (C6-C12)bicycloalkyl, heterocycle, heterocyclyl(C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, heteroaryl, heteroaryl(C1-C8)alkyl, —CO2Ra, RaC(═O)O—, RaC(═O)—, —OCO2Ra, RaRbNC(═O)O—, RbOC(═O)N(Ra)—, RaRbN—, RaRbNC(═O)—, RaC(═O)N(Rb)—, RaRbNC(═O)N(Rb)—, RaRbNC(═S)N(Rb)—, RaOC(═S)—, RaC(═S)—, —SSRa, and RaS(═O)— or two R6 groups and the atom to which they are attached combine to form C═O or C═S, or wherein two R6 groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring;
• R7 and R8 are each independently hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, aryl or aryl(C1-C8)alkylene, heteroaryl, heteroaryl(C1-C8)alkylene-;
• or wherein R7 and R8 together with the nitrogen atom to which they attach form a heterocycle or heteroaromatic ring;
• R9 and R10 are each independently selected from the group consisting of hydrogen, halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3, —SCH3, (C1-C8)alkyl, aryl and aryl(C1-C8)alkyl, wherein R9 and R10 are optionally substituted with 1 to 4 substituents of Ra, wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, —SO—, —S(O)2— or amino (—NRa—), or where R9 and R10 are independently absent, with the proviso that Ra is not SH or halogen in the case where the R9 or R10 to which Ra is bound is halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3 or —SCH3;
• Ra and Rb are each independently selected from the group consisting of hydrogen, halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3, —SCH3, propargyl, cyano, —OS(O2)H, —OS(O2)OH, —OS(O2)CH3, —OS(O2)OCH3, (C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, (C3-C8)cycloalkyl, (C6-C12)bicycloalkyl, cycloalkyl(C1-C8)alkyl, bicycloalkyl(C6-C12)alkyl, heteroaryl and heteroaryl(C1-C8)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 (—NRc—);
• and wherein the alkyl, cycloalkyl, aryl and heteroaryl are optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of —ORc, —NRcRc, SRc, cyano, —OS(O2)H, —OS(O2)OH, —OS(O2)CH3 and —OS(O2)OCH3, provided that the point of attachment of Ra or Rb is not a heteroatom when it is attached to another heteroatom;
• Rc is selected from the group consisting of hydrogen and (C1-C8)alkyl;
• and
• m is 0 to 8;
• n is 0, 1, 2 or 3, provided that when n is 0, Y is not —NR4R5;
• or
• a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

A method for treating cancer, comprising:

• administering a therapeutically effective amount of an A2A antagonist compound of formula I a mammal in need of such treatment:
• wherein:
• R1 and R2 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 Ra groups;
• Y is —CR3R4R5 or NR4R5;
• R3 is selected from the group consisting of hydrogen, halo, —ORa, —SRa, (C1-C8)alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C3-C8)cycloalkyl, heterocycle, heterocycle(C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, heteroaryl, heteroaryl(C1-C8)alkyl, —CO2Ra, RaC(═O)O—, RaC(═O)—, —OCO2Ra, RaRbNC(═O)O—, RbOC(═O)N(Ra)—, RaRbN—, RaRbNC(═O)—, RaC(═O)N(Rb)—, RaRbNC(═O)N(Rb)—, RaRbNC(═S)N(Rb)—, RaOC(═S)—, RaC(═S)—, —SSRa, RaS(═O)—, and RaS(═O)2—;
• or if the ring formed from the group CR3R4R5 is aryl or heteroaryl or partially unsaturated, then R3 can be absent;
• R4 and R5 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 (—NRa—) in the ring, wherein any ring comprising R4 and R5 is optionally further substituted with from 1 to 14 R6 groups;
• wherein each R6 is independently selected from the group consisting of halo, —ORa, —SRa, substituted or unsubstituted (C1-C8)alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C3-C8)cycloalkyl, (C6-C12)bicycloalkyl, heterocycle, heterocyclyl(C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, heteroaryl, heteroaryl(C1-C8)alkyl, —CO2Ra, RaC(═O)O—, RaC(═O)—, —OCO2Ra, RaRbNC(═O)O—, RbOC(═O)N(Ra)—, RaRbN—, RaRbNC(═O)—, RaC(═O)N(Rb)—, RaRbNC(═O)N(Rb)—, RaRbNC(═S)N(Rb)—, RaOC(═S)—, RaC(═S)—, —SSRa, and RaS(═O)— or two R6 groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R6 groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring;
• R7 and R8 are each independently hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, aryl or aryl(C1-C8)alkylene, heteroaryl, heteroaryl(C1-C8)alkylene-;
• or wherein R7 and R8 together with the nitrogen atom to which they attach form a heterocycle or heteroaromatic ring;
• R9 and R10 are each independently selected from the group consisting of hydrogen, halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3, —SCH3, (C1-C8)alkyl, aryl and aryl(C1-C8)alkyl, wherein R9 and R10 are optionally substituted with 1 to 4 substituents of Ra, wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, —SO—, —S(O)2— or amino (—NRa—), or where R9 and R10 are independently absent, with the proviso that Ra is not SH or halogen in the case where the R9 or R10 to which Ra is bound is halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3 or —SCH3;
• Ra and Rb are each independently selected from the group consisting of hydrogen, halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3, —SCH3, propargyl, cyano, —OS(O2)H, —OS(O2)OH, —OS(O2)CH3, —OS(O2)OCH3, (C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, (C3-C8)cycloalkyl, (C6-C12)bicycloalkyl, cycloalkyl(C1-C8)alkyl, bicycloalkyl(C6-C12)alkyl, heteroaryl and heteroaryl(C1-C8)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 (—NRc—);
• and wherein the alkyl, cycloalkyl, aryl and heteroaryl are optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of —ORc, —NRcRc, SRc, cyano, —OS(O2)H, —OS(O2)OH, —OS(O2)CH3 and —OS(O2)OCH3, provided that the point of attachment of Ra or Rb is not a heteroatom when it is attached to another heteroatom;
• Rc is selected from the group consisting of hydrogen and (C1-C8)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 —NR4R5;
• or
• a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

A method for treating cancer, comprising:

• administering a therapeutically effective amount of an A2A antagonist compound of formula I a mammal in need of such treatment:
• wherein:
• R7 and R8 are each independently selected from the group consisting of hydrogen, (C1-C8)alkyl-, aryl(C1-C8)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 (—NRa—) in the ring, and each is optionally substituted with from 1, 2, 3 or 4 Ra groups;
• Y is —CR3R4R5 or NR4R5;
• 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, (C3-C8)cycloalkyl, (C6-C12)bicycloalkyl, (C6-C20)polycyclyl, heterocyclyl, cycloalkyl(C1-C8)alkyl, bicycloalkyl(C6-C12)alkyl, heterocyclyl(C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, heteroaryl, heteroaryl(C1-C8)alkyl, —NRaRb, —SRa, cyano, nitro, trifluoromethyl, trifluoromethoxy, —CO2Ra, RaC(═O)O—, RaC(═O)—, —OCO2Ra, RaRbNC(═O)O—, RbOC(═O)NRa—, RaRbNC(═O)—, RaC(═O)NRb—, RaRbNC(═O)NRb—, RaRbNC(═S)NRb—, RaOC(═S)—, RaC(═S)—, —SSRa, RaS(═O)—, —OS(O2)Ra, OS(═O)ORa, —OS(O2)ORa and —O(SO2)NRaRb;
• R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3, —SCH3, (C1-C8)alkyl, aryl and aryl(C1-C8)alkyl, wherein R1 and R2 are optionally substituted with 1 to 4 substituents of Ra, wherein the alkyl is optionally interrupted by 1-4 heteroatoms selected from —O—, —S—, —SO—, —S(O)2— or amino (—NRa), or where R1 and R2 are independently absent, with the proviso that Ra is not SH or halogen when the R1 or R2 to which Ra is bound is halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3 or —SCH3;
• R3 is selected from the group consisting of hydrogen, halo, —ORa, —SRa, (C1-C8)alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C3-C8)cycloalkyl, heterocycle, heterocycle(C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, heteroaryl, heteroaryl(C1-C8)alkyl, —CO2Ra, RaC(═O)O—, RaC(═O)—, —OCO2Ra, RaRbNC(═O)O—, RbOC(═O)N(Ra)—, RaRbN—, RaRbNC(═O)—, RaC(═O)N(Rb)—, RaRbNC(═O)N(Rb)—, RaRbNC(═S)N(Rb)—, RaOC(═S)—, RaC(═S)—, —SSRa, RaS(═O)—, and RaS(═O)2—;
• or if the ring formed from the group CR3R4R5 is aryl or heteroaryl or partially unsaturated, then R3 can be absent;
• R4 and R5 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 (—NRa—) in the ring, wherein any ring comprising R4 and R5 is optionally further substituted with from 1 to 14 R6 groups;
• wherein each R6 is independently selected from the group consisting of halo, —ORa, —SRa, substituted or unsubstituted (C1-C8)alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C3-C8)cycloalkyl, (C6-C12)bicycloalkyl, heterocycle, heterocyclyl(C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, heteroaryl, heteroaryl(C1-C8)alkyl, —CO2Ra, RaC(═O)O—, RaC(═O)—, —OCO2Ra, RaRbNC(═O)O—, RbOC(═O)N(Ra)—, RaRb—, RaRbNC(═O)—, RaC(═O)N(Rb)—, RaRbNC(═O)N(Rb)—, RaRbNC(═S)N(Rb)—, RaOC(═S)—, RaC(═S)—, —SSRa, and RaS(═O)— or two R6 groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R6 groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring;
• R9 and R10 are each independently selected from the group consisting of hydrogen, halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3, —SCH3, (C1-C8)alkyl, aryl and aryl(C1-C8)alkyl, wherein R9 and R10 are optionally substituted with 1 to 4 substituents of Ra, wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, —SO—, —S(O)2— or amino (—NRa—), or where R9 and R10 are independently absent, with the proviso that R3 is not SH or halogen in the case where the R9 or R10 to which Ra is bound is halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3 or —SCH3;
• Ra and Rb are each independently selected from the group consisting of hydrogen, halogen, —NH2, —OH, —SH, —NHCH3, —N(CH3)2, —OCH3, —SCH3, propargyl, cyano, —OS(O2)H, —OS(O2)OH, —OS(O2)CH3, —OS(O2)OCH3, (C1-C8)alkyl, aryl, aryl(C1-C8)alkyl, (C3-C8)cycloalkyl, (C6-C12)bicycloalkyl, cycloalkyl(C1-C8)alkyl, bicycloalkyl(C6-C12)alkyl, heteroaryl and heteroaryl(C1-C8)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 (—NRc—);
• and wherein the alkyl, cycloalkyl, aryl and heteroaryl are optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of —ORc, —NRcRc, SRc, cyano, —OS(O2)H, —OS(O2)OH, —OS(O2)CH3 and —OS(O2)OCH3, provided that the point of attachment of Ra or Rb is not a heteroatom when it is attached to another heteroatom;
• Rc is selected from the group consisting of hydrogen and (C1-C8)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 —NR4R5;
• or
• a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.