Monoacylglycerol Lipase Modulators

A method of treating a subject suffering from or diagnosed with a disease, disorder, or condition mediated by MGL receptor activity, comprising administering to a subject in need of such treatment a therapeutically effective amount of at least one compound of Formula (I):

• wherein:
• R2 is selected from the group consisting of:
• (a)
• (b) pyridyl substituted with OC1-4haloalkyl;
• (c) pyrazole or 1H-1,2,4-triazole each substituted with one or two members each independently selected from the group consisting of:
• H, Cl, C1-4alkyl, cyclopropyl and phenyl;
• (d)
• (e)
• (f)
• and
• (g)
• where X is selected from the group consisting of:
• O, S, NH, and NCH3;
• Ra is H or halo;
• Rb is selected from the group consisting of:
• H, halo and CH3;
• Rc is H or CF3;
• and
• Rd is H or CH3;
• R3 is selected from the group consisting of:
• (h) Phenyl;
• or phenyl independently substituted with one or two members selected from the group consisting of:
• halo and OC1-4haloalkyl;
• (i)
• and
• (j) C3-4cycloalkyl;
• and
• R4 is selected from the group consisting of:
• C1-4alkyl;
• with the proviso that when R2 is
• then R3 is cyclopropyl;
• and pharmaceutically acceptable salts, isotopes, N-oxides, solvates, and stereoisomers of compounds of Formula (I).

A method of treating a subject suffering from or diagnosed with a disease, disorder, or condition mediated by MGL receptor activity, comprising administering to a subject in need of such treatment a therapeutically effective amount of at least one compound of Formula (II):

• wherein
• R1 is C1-4alkyl;
• R2a is selected from the group consisting of:
• (a)
• (b) 6-Membered heteroaryl selected from the group consisting of:
• (c) 5-Membered heteroaryl selected from the group consisting of:
• (d) 5,6-Fused or 6,5-fused heteroaryl selected from the group consisting of:
• (e) Fused 6,6 heteroaryl selected from the group consisting of:
• and
• (f) Heterocycloalkyl selected from the group consisting of:
• R3a is selected from the group consisting of:
• (g) Phenyl;
• or phenyl substituted with one, two, or three members each independently selected from the group consisting of:
• halo, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl, and OC1-6haloalkyl;
• (h) 5-Membered heteroaryl selected from the group consisting of:
• (i) 6-Membered heteroaryl selected from the group consisting of:
• and
• (j) 5,6-Fused or 6,5-fused heteroaryl selected from the group consisting of:
• and
• (k) Heterocycloalkyl selected from the group consisting of:
• Re is selected from the group consisting of:
• OC1-4alkyl, OC1-4haloalkyl, (C═O)NHCH3, and 5-membered heteroaryl ring containing two or three nitrogen members, wherein the 5-membered heteroaryl ring is optionally substituted with one Rf member;
• Rf is selected from the group consisting of:
• H, halo, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl, and OC1-4haloalkyl;
• Rg is selected from the group consisting of:
• OC1-4alkyl, OC1-4haloalkyl, CH2OCH3, CH2OH,
• Rh is selected from the group consisting of:
• H, C1-4alkyl, C1-4haloalkyl, and C3-6cycloalkyl;
• Ri is selected from the group consisting of:
• H, halo, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl, C3-6cycloalkyl, and C3-6cycloalkyl substituted with one or two members independently selected from:
• F and CH3;
• Rj is selected from the group consisting of:
• H, halo, C1-4alkyl and C1-4haloalkyl;
• Rk is selected from the group consisting of:
• H, halo, OH, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl, and OC1-4haloalkyl;
• Rm is H or C1-4alkyl;
• Rn is selected from the group consisting of:
• H, halo and OC1-4alkyl;
• Ro is selected from the group consisting of:
• H, C1-4alkyl, and C1-4haloalkyl;
• Rp is selected from the group consisting of:
• H, C1-4alkyl, and OC1-4alkyl;
• Y is CH or N;
• and
• R4a is selected from the group consisting of:
• CH3, CF2H, CF3, C3-6cycloalkyl, and phenyl;
• and pharmaceutically acceptable salts, isotopes, N-oxides, solvates, and stereoisomers of compounds of Formula (II).