Therapeutic compounds

A method for producing analgesia in an animal comprising administering to the animal a compound of formula Ia′:

• or a pharmaceutically acceptable salt thereof and further comprising administering acetaminophen to the animal;
• i) wherein the compound of formula Ia′:
• ring A is phenyl, wherein the phenyl, is optionally substituted with one or more groups independently selected from the group consisting of C1-4 alkyl, C1-4 haloalkyl, C3-8 cycloalkyl, —F, —Cl, —Br, —I, —ORa, —SRa, —N(Ra)2, —NO2 and —CN;
• L is selected from the group consisting of:
• RL is hydrogen, C1-4 alkyl, C1-4 haloalkyl or C3-8 cycloalkyl;
• R6 is hydrogen, or C1-6 alkyl that is optionally substituted with one or more groups selected from —F, —Cl, —Br, —I, —ORf, —SRf, —N(Rf)2, oxo, —NO2 or —CN;
• or R6 and R8 taken together with the atoms to which they are attached form a heterocycle that is optionally substituted with one or more groups selected from —F, —Cl, —Br, —I, —ORi, —SRi, —N(Ri)2, —NO2 or —CN;
• R7 is hydrogen, or C1-6 alkyl that is optionally substituted with one or more groups selected from —F, —Cl, —Br, —I, —ORg, —SRg, —N(Rg)2, oxo, —NO2 or —CN;
• R8 is hydrogen, or C1-6 alkyl that is optionally substituted with one or more groups selected from —F, —Cl, —Br, —I, —ORh, —SRh, —N(Rh)2, oxo, —NO2 or —CN;
• or R6 and R8 taken together with the atoms to which they are attached form a heterocycle that is optionally substituted with one or more groups selected from —F, —Cl, —Br, —I, —ORi, —SRi, —N(Ri)2, —NO2 or —CN;
• X is ═O, ═S or ═N—Rx;
• wherein Rx is hydrogen, or C1-6 alkyl that is optionally substituted with one or more groups selected from —F, —Cl, —Br, —I, —ORi, —SRi, —N(Ri)2, —NO2 or —CN;
• or Rx and R8 taken together with the nitrogen atoms to which they are attached form a heteroaryl or an unsaturated heterocycle;
• wherein the heteroaryl and hetrocycle are optionally substituted with one or more groups selected from —F, —Cl, —Br, —I, —ORi, —SRi, —N(Ri)2, —NO2 or —CN;
• each Ra is independently hydrogen, C1-4 alkyl or C1-4 haloalkyl, wherein the C1-4 alkyl and C1-4 haloalkyl are optionally substituted with aryl or heteroaryl;
• or two Ra groups taken together with the nitrogen to which they are attached form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
• each Rf is independently hydrogen, C1-4 alkyl or C1-4 haloalkyl;
• or two Rf groups taken together with the nitrogen to which they are attached form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
• each Rg is independently hydrogen, C1-4 alkyl or C1-4 haloalkyl;
• or two Rg groups taken together with the nitrogen to which they are attached form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
• each Rh is independently hydrogen, C1-4 alkyl or C1-4 haloalkyl;
• or two Rh groups taken together with the nitrogen to which they are attached form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
• and
• each Ri is independently hydrogen, C1-4 alkyl or C1-4 haloalkyl;
• or two Ri groups taken together with the nitrogen to which they are attached form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
• wherein the analgesia is produced for synergy in antinociception with reduced sedation or cardiovascular effects.