2-polycyclic propynyl adenosine analogs having A2A agonist activity

A compound having formula (I):

• wherein
• each R1 is independently hydrogen, halo, —ORa, —SRa, (C1-C8)alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, C3-8cycloalkyl, heterocycle, heterocycle(C1-C8)alkylene-, aryl, aryl(C1-C8)alkylene-, heteroaryl, heteroaryl(C1-C8)alkylene-, —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)—, —OPO3Ra, RaOC(═S)—, RaC(═S)—, —SSRa, RaS(═O)—, RaS(═O)2—, —N═NRa, or —OPO2Ra;
• each R2 is independently hydrogen, halo, (C1-C8)alkyl, (C3-C8)cycloalkyl, heterocycle, heterocycle(C1-C8)alkylene-, aryl, aryl(C1-C8)alkylene-, heteroaryl, or heteroaryl(C1-C8)alkylene-;
• or
• R1 and R2 and the atom to which they are attached is C═O, C═S or C═NRc.
• Z is
• wherein each Z group is optionally substituted with from 1 to 10 R6 groups;
• wherein each R6 is independently hydrogen, halo, —ORa, —SRa, (C1-C8)alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C1-C8)cycloalkyl, (C1-C8)cycloalkyl-(C1-C8)alkylene-, (C6-C12)bicycloalkyl, heterocycle or heterocycle (C1-C8)alkylene-, aryl, aryl (C1-C8)alkylene-, heteroaryl, heteroaryl(C1-C8)alkylene-, —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)—, —OPO3Ra, RaOC(═S)—, RaC(═S)—, —SSRa, RaS(═O)—, —NNRa, —OPO2Ra, or two R6 groups and the atom to which they are attached is C═O, or C═S;
• or two R6 groups together with the atom or atoms to which they are attached can form a carbocyclic or a heterocyclic ring comprising from 1 to 6 carbon atoms and 1, 2, 3, or 4 heteroatoms selected from non-peroxide oxy (—O—), thio (—S—), sulfinyl (—SO—), sulfonyl (—S(O)2—), phosphine (—OP(O)2—, or amine (—NRa—) in the ring;
• each R7 is independently hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C1-C8)cycloalkyl(C1-C8)alkylene-, heterocycle, heterocycle (C1-C8)alkylene-, aryl, aryl(C1-C8)alkylene, heteroaryl, or heteroaryl(C1-C8)alkylene-;
• X is —CH2ORe, —CO2Re, —CH2OC(O)Re, —C(O)NReRf, —CH2SRe, C(S)ORe, —CH2OC(S)Re or C(S)NReRf—CH2N(Re)(Rf), or a group having the formula
• wherein each Z1 is non-peroxide —O—, —S(O)p—, —C(R8)j—, or —N(R8)—;
• provided that at least one Z1 is non-peroxide —O—, —S(O)p—, or —N(R8)—;
• each R8 is independently hydrogen, (C1-C8)alkyl, (C1-C8)alkenyl, (C3-C8)cycloalkyl, (C1-C8)alkyl(C3-C8)cycloalkyl, (C3-C8)cycloalkenyl, (C1-C8)alkyl-(C3-C8)cycloalkenyl, aryl, aryl(C1-C8)alkylene, heteroaryl, or heteroaryl-(C1-C8)alkylene-;
• wherein any of the alkyl or alkenyl groups of R8 are optionally interrupted by —O—, —S—, or —N(Ra)—;
• Re is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl;
• Rf is hydrogen, (C1-C8)alkyl, or (C1-C8)alkyl substituted with 1-3 (C1-C8)alkoxy, (C3-C8)cycloalkyl, (C1-C8)alkylthio, amino acid, aryl, aryl(C1-C8)alkylene, heteroaryl, or heteroaryl(C1-C8)alkylene;
• and
• wherein any of the alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycle, aryl, or heteroaryl, groups of R1, R2, R6, R7 and R8 is optionally substituted on carbon with one or more (e.g. 1, 2, 3, or 4) substituents selected from the group consisting of halo, —ORa, —SRa, (C1-C8)alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C3-C8)cycloalkyl, (C6-C12)bicycloalkyl, heterocycle or heterocycle(C1-C8)alkylene-, aryl, aryloxy, aryl (C1-C8)alkylene-, heteroaryl, heteroaryl(C1-C8)alkylene-, —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)—, —OPO3Ra, RaOC(═S)—, RaC(═S)—, —SSRa, RaS(═O)p—, RaRbNS(O)p—, N═NRa, and —OPO2Ra;
• wherein any (C1-C8)alkyl, (C3-C8)cycloalkyl, (C6-C12)bicycloalkyl, (C1-C8)alkoxy, (C1-C8)alkanoyl, (C1-C8)alkylene, or heterocycle, is optionally partially unsaturated;
• Ra and Rb are each independently hydrogen, (C1-C8)alkyl, or (C1-C8)alkyl substituted with 1-3 (C1-C8)alkoxy, (C3-C8)cycloalkyl, (C1-C8)alkylthio, amino acid, aryl, aryl(C1-C8)alkylene, heteroaryl, or heteroaryl(C1-C8)alkylene;
• or Ra and Rb, together with the nitrogen to which they are attached, form a pyrrolidino, piperidino, morpholino, or thiomorpholino ring;
• and
• Rc is hydrogen or (C1-C6)alkyl;
• m is 0, 1, 2, 3, 4, 5, 6, 7, or 8;
• i is 1, or 2;
• each j is independently 1, or 2;
• and each p is independently 0, 1, or 2;
• or
• a pharmaceutically acceptable salt thereof.