Uses of substituted imidazoheterocycles

A method of prophylaxis, treatment or inhibition of a cannabinoid receptor-associated disease, disorder or condition in a mammalian subject, the method comprising administering to the subject a compound having the structure of formula I or a pharmaceutically acceptable salt, acid salt, hydrate or stereoisomer thereof, wherein the cannabinoid receptor-associated disease, disorder or condition is pain or an inflammatory disease, disorder or condition:

• and wherein formula I is as follows:
• Y is selected from the group consisting of NRa and N+R1R2 X−;
• Z is selected from the group consisting of a bond, —(CH2)p, —CH═CH—, —C≡C—, —CONH— and —CO—;
• Ra is selected from the group consisting of —H, C1-C8 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, aryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, —SO2R3, —COR3, —CONR3R4, —CSNR3R4, —COOR3 and —(CH2)qheterocyclyl, wherein the alkyl, cycloalkyl, cycloalkenyl, aryl and heterocyclyl of Ra are each optionally substituted with one to four substituents independently selected from the group consisting of halo, —OH, oxo, —NH2, —NO2, —CN, —COOH, —COR3, —OCF3, —CF3, C1-C6 alkyl, C1-C4 alkoxy, C3-C8 cycloalkyl, phenyl, trifluoromethoxy and trifluoromethyl;
• Rb is selected from the group consisting of C1-C8 alkyl, C2-C8 alkenyl, aryl, —NR5R6,
• wherein the alkyl, alkenyl and aryl of Rb are each optionally substituted with one to three substituents independently selected from the group consisting of C1-C4 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl, alkoxy, aryl, 5-, 6-, and 7-membered heterocyclyl, halo, —OH, —NH2, —CN and —NO2;
• Rc is selected from the group consisting of halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C3-C8 cycloalkenyl, C1-C4 alkoxy, aryl, 5-, 6-, 7-, 8-, 9-, and 10-membered heterocyclyl;
• wherein the C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C3-C8 cycloalkenyl, aryl, 5-, 6-, 7-, 8-, 9- and 10-membered heterocyclyl of Rc are optionally substituted with one to five substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C3-C6 cycloalkyl, C4-C8 cycloalkenyl, halo, —OH, —NH2, (A)(A′)(A″)(A′″)aryl, (A)(A′)(A″)(A′″)heterocyclyl, NR14R15, (CH2)pNR14R15, —CN, —NO2, oxo, —COOR14, SOR16, SO2R16, SO2NR14R15, NR15SO2R16, COR14, CONR14R15 and NR15COR16;
• wherein (A), (A′), (A″) and (A′″) are each an independently selected from the group consisting of —H, halo and C1-C4 alkyl and each heterocyclyl of (A)(A′)(A″)(A′″)heterocyclyl is independently selected from the group consisting of 5-, 6-, 7-, 8-, 9- and 10-membered heterocyclyl;
• R1 and R2 are each independently C1-C4 alkyl;
• R3 and R4, when either or both are present, are each independently selected from the group consisting of —H, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl, 4-, 5-, 6-, 7- and 8-membered heterocyclyl;
• wherein the alkyl, alkenyl, alkynyl, cycloalkyl of R3 and R4 are each independently optionally substituted with one to three substituents independently selected from the group consisting of C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C1-C4 alkoxy, C1-C4 acyl, aryl, 5-, 6-, 7-, 8-, 9- and 10-membered heterocyclyl, —NH2, —NO2, —CN, —OH, —COOH, oxo, and halo;
• provided that if Ra is SO2R3, then R3 is not —H;
• alternatively, R3 and R4 taken together with the nitrogen atom to which they are bonded form a heterocyclyl selected from the group consisting of 4-, 5-, 6-, 7- and 8-membered heterocyclyl;
• R5 is selected from the group consisting of —H, C1-C8 alkyl and C1-C4 haloalkyl;
• wherein the alkyl and haloalkyl of R5 are optionally substituted with one to four substituents independently selected from the group consisting of C1-C4 alkoxy, —OH, —NH2, oxo and —CN;
• R6 is selected from the group consisting of —H, —CR10R11R12, —CR10R11COR13, C1-C8 alkyl, C3-C10 cycloalkyl, aryl, haloaryl, (CH2)q-linked 5-, to 10-membered heterocyclyl;
• wherein the alkyl, cycloalkyl, aryl, and heterocyclyl of R6 are optionally substituted with one to three substituents independently selected from the group consisting of C1-C4 alkyl, aryl, halo, —OH, C1-C4 alkoxy, C1-C4 hydroxyalkyl, —COR13, CONHCH3, —SO2R11, —SO2NR8R9, —NH2, —NHCO—(C1-C4 alkyl), —NHSO2—(C1-C4 alkyl), —CN, —NO2 and 5- to 10-membered heterocyclyl;
• alternatively, R5 and R6 taken together with the nitrogen atom to which they are bonded form a heterocyclyl selected from the group consisting of 5- to 10-membered heterocyclyl, which heterocyclyl substituent of R6 is optionally substituted with one to two substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 haloalkyl, COOR1, —CONR1R2, halo, oxo and (CH2)q-linked 5-, to 10-membered heterocyclyl;
• R7 is selected from the group consisting of —COR3, —COOR3, —SO2R3, and 5-, 6- and 7-membered heterocyclyl;
• R8 and R9 are independently selected from the group consisting of —H, C1-C6 alkyl, C1-C6 hydroxyalkyl, C1-C6 alkylaminoalkyl, C1-C6 alkoxyalkyl, C1-C6 cyanoalkyl, C1-C4 haloalkyl, C1-C4 aminoacyl, C1-C4 alkoxy, C1-C6 alkyl-NHSO2CH3, C2-C4 alkenyl, (B)(B′)C3-C10 cycloalkyl, aryl, (CH2)q-linked 5- to 10-membered (B)(B′)heterocyclyl, halo, —OH, C1-C4 alkoxy, C1-C4 alkyl, —CONH2, —NH2, —CN and —NO2;
• wherein (B) and (B′) are each independently —H, —OH, C1-C4 alkyl, C1-C4 hydroxyalkyl or C1-C4 acyl, alternatively:
• (i) R8 and R9, taken together with the nitrogen atom to which they are bonded form a heterocyclyl moiety or an 8- to 10-membered spiro-bicyclic heterocyclyl each of which are optionally substituted with one to three substituents selected from the group consisting of C1-C4 alkyl, C1-C4 haloalkyl, halo, —(CH2)q—OH, oxo, COOR1, SO2CH3, C1-C4 acyl —(CH2)q—CN and aryl;
• or (ii) R8 and R9, taken together with the carbon atom to which they are bonded form a cycloalkyl which is optionally substituted with one to three substituents selected from the group consisting of C1-C4 alkyl, C1-C4 haloalkyl, halo, —OH, oxo and aryl;
• R10 is selected from the group consisting of —H and C1-C4 alkyl;
• R11 is selected from the group consisting of —H, C1-C8 alkyl, C2-C6 alkenyl, C2-C4 alkynyl, C3-C10 cycloalkyl, aryl, 5-, 6-, 7-, -8-, 9- and 10-membered —(CH2)qheterocyclyl;
• wherein the alkyl, alkenyl, alkynyl, cycloalkyl, aryl and 5-, 6-, 7-, 8-, 9- and 10-membered heterocyclyl of R11 are optionally substituted with one to three substituents independently selected from the group consisting of C1-C4 alkyl, C3-C6 cycloalkyl, haloaryl, aryl, and 5-, 6-, 7-8-, 9- and 10-membered heterocyclyl, halo, —OH, C1-C4 alkoxy, —NH2, -guanidino, —CN, —NO2, oxo, —COOR10, —CONR8R9, —SO2NR8R9, —SR10, —SORT and —SO2R1;
• R12 is selected from the group consisting of —H, C1-C4 alkyl and C1-C4 hydroxyalkyl;
• R13 is selected from the group consisting of —OR10 and —NR8R9;
• R14 and R15 are each independently selected from the group consisting of —H, C1-C4 alkyl and aryl;
• alternatively, R14 and R15 taken together with the nitrogen atom to which they are bonded form a heterocyclyl selected from the group consisting of 5-, 6-, 7-8-, 9- and 10-membered heterocyclyl;
• R16 is C1-C4 alkyl or aryl;
• X− is an anionic counterion;
• m is an integer from 1 to 3;
• each instance of p is independently an integer from 1 to 6;
• and each instance of q is independently zero or an integer from 1 to 4;
• and
• provided that when Rc is heterocyclyl, the heterocyclyl is directly bonded through a carbon atom of a ring of the heterocyclyl.