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-C8)cycloalkyl, heterocycle, heterocyclic(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;
• each R6 is independently halo, —ORa, —SRa, (C1-C8)alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C1-C8)cycloalkyl, (C6-C12)bicycloalkyl, heterocycle or heterocyclic(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, 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 (—S—-), 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, aryl or aryl(C1-C8)alkylene, heteroaryl, heteroaryl(C1-C8)alkylene-;
• X is —CH2ORa, —CO2Ra, —CH2OC(O)Ra, —C(O)NRaRb, —CH2SRa, —C(S)ORa, —CH2OC(S)Ra or C(S)NRaRb or —CH2N(Ra)(Rb);
• wherein any of the alkyl, cycloalkyl, heterocycle, aryl, or heteroaryl, groups of R1, R2, R6 and R7 is optionally substituted on carbon with one or more (e.g. 1, 2, 3, or 4) substituents selected from the group consisting of halo, —ORf, —SRf, (C1-C8)alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C3-C8)cycloalkyl, (C6-C12)bicycloalkyl, heterocycle or heterocyclic(C1-C8)alkylene-, aryl, aryloxy, aryl (C1-C8)alkylene-, heteroaryl, heteroaryl(C1-C8)alkylene-, —CO2Rf, RfC(═O)O—, RfC(═O)—, —OCO2Rf, RfRgNC(═O)O—, RgOC(═O)N(Rf)—, RfRgN—, RfRgNC(═O)—, RfC(═O)N(Rg)—, RfRgNC(═O)N(Rg)—, RfRgNC(═S)N(Rg)—, —OPO3Rf, RfOC(═S)—, RfC(═S)—, —SSRf, RfS(═O)p—, RfRgNS(O)p—, N═NRf, and —OPO2Rf;
• 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, 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;
• Rf and Rg are each independently hydrogen, (C1-C8)alkyl, or (C1-C8)alkyl substituted with 1-3 (C1-C8)alkoxy, (C3-C8)cycloalkyl, (C1-C8)alkylthio;
• aryl, aryl(C1-C8)alkylene, heteroaryl, or heteroaryl(C1-C8)alkylene;
• or Rf and Rg, 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 and p is 1,or 2;
• or
• a pharmaceutically acceptable salt thereof.